Impact of reflux esophagitis on the esophageal function before and after laparoscopic fundoplication

Abstract

Background

High-resolution manometry (HRM), which is breakthrough testing equipment to evaluate esophageal motor function, was developed in Europe and United State and has garnered attention. Moreover, multichannel intraluminal impedance pH (MII-pH) testing has allowed us to grasp all liquid/gas reflux including not only acid but also non-acid reflux. We examined the impact of the presence of reflux esophagitis (RE) on esophageal motor function before and after laparoscopic fundoplication.

Materials and methods

The subjects included 100 patients (male: 63 patients, mean age: 54.1 ± 15.8) among 145 patients who underwent laparoscopic fundoplication for GERD associated diseases during a 4-year period from October 2012 to September 2016, excluding 6 patients who underwent further surgery, 32 patients on whom HRM was not performed, 3 patients who had technical errors during testing, and 4 patients for whom the status of RE was unknown. Regarding HRM, Mano Scan from Given Imaging Ltd. was used, and for the analysis, Mano View version 3.0 from the same company was used, after which data was calculated based on the Chicago Classification advocated by Pandolfino et al. Moreover, for the MII-pH testing, Sleuth manufactured by Sandhill Scientific. Inc. was used and automatic analysis was conducted by a computer. Postoperative assessments were conducted 3 months following surgery for all. Data was described in the median value and inter-quartile range, with a statistically significant difference defined as p < 0.05 by Chi square, Mann–Whitney, and Wilcoxon tests.

Results

RE+ group (Los Angeles classification A:B:C:D = 7:9:16:12 patients) included 44 patients (44%), of older age compared to the RE− group (62 vs. 50 years, p = 0.012) and a higher Body Mass Index value (24.0 vs. 22.5, p = 0.045); however, no differences were observed in terms of gender and duration of symptoms. In the preoperative findings on MII-pH, the RE+ group demonstrated significantly longer acid reflux time (4.7 vs. 1.3%, p = 0.005), while in the HRM findings, the RE− group demonstrated a significantly longer abdominal esophagus (0 vs. 0.4 cm, p = 0.049) and maintained esophageal body motor function (DCI: 1054 vs. 1407 mmHg s cm, p = 0.021, Intact peristalsis ratio: 90 vs. 100%, p = 0.037). As to the comparison of the treatment effect before and after laparoscopic fundoplication (Toupet fundoplication for all), significant improvements were observed in both groups in various parameters regarding reflux including acid reflux time, total number of liquid reflux episodes and total number of reflux episodes. Moreover, for both groups, the total length of the lower esophageal sphincter (LES) (RE+ group: 2.7 vs. 3.2 cm, p = 0.001, RE− group: 3.0 vs. 3.4 cm, p = 0.003) and the total length of the abdominal esophagus (RE+ group: 0 vs. 1.6 cm, p < 0.001, RE− group: 0 vs. 1.8 cm, p = 0.001) were significantly extended following surgery; however, no change was observed in DCI before and after surgery.

Conclusions

Regardless of the presence of RE, cardiac function and LES function were improved following laparoscopic Toupet fundoplication, but no changes were observed in esophageal body motor function.

https://ift.tt/2r075ou

Randomised clinical trial: a leucine‐metformin‐sildenafil combination (NS‐0200) vs placebo in patients with non‐alcoholic fatty liver disease

Alimentary Pharmacology &Therapeutics, EarlyView.


https://ift.tt/2Hw2kcP

A Short-Term Longitudinal Exploration of the Impact of TV Exposure on Objectifying Attitudes Toward Women in Early Adolescent Boys

Abstract

The present study aimed to examine the relationships over time between television viewing (music and tween TV) and boys' endorsement of sexualized gender roles, that is, views of women as sex objects and men as sexually dominant, as well as a tendency to objectify women's bodies. As an additional question, we were interested in how parental socialization to gender roles related to these pathways. A sample of 496 Belgian boys aged 11.18 years (SD = 1.06, range = 9–13), participated in a longitudinal study and completed measures three times at 6-month intervals. Findings revealed that music TV was associated with increases in views of men as sexually dominant. Tween TV was associated with increases in views of women as sex objects, which in turn was associated with increased objectification of women's bodies among adolescents who experienced high levels of gender-typical socialization from their parents. These findings suggest that media exposure among early adolescent boys may contribute to the development of sexually objectifying attitudes toward women. In addition, they highlight the critical role of parents in modulating the effect of media exposure and suggest the usefulness of engaging parents in interventions aiming to decrease these deleterious effects.

https://ift.tt/2JsfmbO

Berbamine suppresses cell proliferation and promotes apoptosis in ovarian cancer partially via the inhibition of Wnt/β-catenin signaling

Abstract

Ovarian cancer is a common and lethal cancer affecting women globally. Berbamine is a natural compound from the plant Berberis amurensis, which is used in Chinese traditional medicine. Recent studies have shown the anti-tumor effects of berbamine in several types of cancers but not in ovarian cancer. In the present study, we investigated the potential anti-tumor effects of berbamine in ovarian cancer and explored the underlying molecular mechanisms. Berbamine suppressed the cell viability of ovarian cancer cells in a concentration-dependent manner as revealed by methyl thiazolyl tetrazolium assay. Berbamine also suppressed the cell growth and invasion of ovarian cancer cells as measured by colony formation and cell invasion assays, respectively. Flow cytometry experiments showed that berbamine increased cell apoptotic rate and induced cell cycle arrest at G₀/G₁ phase in ovarian cancer cells. Western blot analysis showed that berbamine increased the protein levels of cleaved caspase-3, cleaved caspase-9, Bax, and decreased the protein level of Bcl-2 in ovarian cancer cells. Quantitative real-time PCR and western blot analysis demonstrated that berbamine treatment inhibited the Wnt/β-catenin signaling in ovarian cancer cells. The inhibitory effects of berbamine on cell viability and invasion of ovarian cancer cells can be partially reversed by lithium chloride (LiCl) treatment. Growth of tumors developed from SKOV3 cells was significantly suppressed in berbamine-treated group, and berbamine treatment enhanced caspase-3 and -9 cleavage and reduced β-catenin protein level in tumor tissues. In summary, berbamine exerts its anti-cancer effects in vitro and in vivo via induction of apoptosis, partially associated with the inhibition of Wnt/β-catenin signaling.

https://ift.tt/2Jr5WNC

miR-223 promotes the doxorubicin resistance of colorectal cancer cells via regulating epithelial–mesenchymal transition by targeting FBXW7

Abstract

Although doxorubicin has become a key drug in cancer treatment, the resistance of colorectal carcinoma to doxorubicin is a major problem in clinical practice. F-box and WD repeat domain-containing 7 (FBXW7) plays important roles in human cancers and is one of the major causes of drug resistance. The miR-223/FBXW7 pathway has been reported to be a crucial clue to the mechanism of chemoresistance in many human cancers, such as gastric cancer, breast cancer, and non-small cell lung cancer. However, it is unclear whether similar mechanisms of doxorubicin resistance are involved in colorectal cancer (CRC). The aim of the current study was to evaluate the role of miR-223/FBXW7 pathway in chemosensitivity in different CRC cell lines and to investigate the relevant underlying mechanisms. We found that high levels of FBXW7 expression were associated with increased doxorubicin sensitivity in different CRC cell lines, and FBXW7 was regulated by miR-223. Overexpression of miR-223 decreased FBXW7 expression and the sensitivity of CRC cells to doxorubicin, while suppression of miR-223 had the opposite effect. Moreover, epithelial–mesenchymal transition (EMT) was proved to be regulated by miR-223/FBXW7 pathway and involved in the drug resistance. In conclusion, miR-223/FBXW7 axis regulates doxorubicin sensitivity through EMT in CRC, which may lead to the development of individualized treatment in clinical practice.

https://ift.tt/2Kgf0X4

Legionella pneumophila effector WipA, a bacterial PPP protein phosphatase with PTP activity

Abstract

The gram-negative bacterium Legionella pneumophila invades human's lung and causes Legionnaires' disease. To benefit its survival and replication in cellular milieu, L. pneumophila secrets at least 330 effector proteins into host cells. We found that the effector WipA has the protein tyrosine phosphatase (PTP) activity but does not depend on the classical CX5R motif for activity, suggesting that WipA is an unconventional PTP. Meanwhile, the presence of three other highly conserved motifs typically seen in protein serine/threonine phosphatases and the poor inhibition of WipA activity by okadaic acid led us to propose that WipA is a bacterial protein phosphatase. In addition, the determination of the 2.55-Å crystal structure of WipA revealed that WipA resembles cold-active protein tyrosine phosphatase (CAPTPase), and therefore very likely shares the same catalytic mechanism.

https://ift.tt/2Fj2cLA

A Potential New Mechanism Linking Type II Diabetes Mellitus and Alzheimer's Disease

BioEssays, EarlyView.


https://ift.tt/2r1HYRq

Reduction of MHC-I expression limits T-lymphocyte-mediated killing of Cancer-initiating cells

Abstract

Background

It has been proposed that cancer establishment, maintenance, and recurrence may be attributed to a unique population of tumor cells termed cancer-initiating cells (CICs) that may include characteristics of putative cancer stem cell-like cells. Studies in lung cancer have shown that such cells can be enriched and propagated in vitro by culturing tumor cells in serum-free suspension as tumorspheres. CICs have been characterized for their phenotype, stem cell-like qualities, and their role in establishing tumor and maintaining tumor growth. Less is known about the interaction of CICs with the immune system.

Methods

We established CIC-enriched tumorspheres from murine TC-1 lung cancer cells, expressing human papillomavirus 16 (HPV-16) E6/E7 antigens, and evaluated their susceptibility to antitumor immune responses both in vitro and in vivo.

Results

TC-1 CICs demonstrated reduced expression of surface major histocompatibility complex (MHC)-I molecules compared to non-CICs. We similarly determined decreased MHC-I expression in five of six human lung cancer cell lines cultured under conditions enriching for CICs. In vivo, TC-1 cells enriched for CICs were resistant to human papillomavirus 16 E6/E7 peptide vaccine-mediated killing. We found that vaccinated mice challenged with CIC enriched tumorspheres demonstrated shorter survivals and showed significantly fewer CD8⁺ tumor infiltrating lymphocytes compared to CIC non-enriched challenged mice. Furthermore, cultured cytotoxic T lymphocytes (CTLs) from vaccinated mice demonstrated reduced capacity to lyse TC-1 cells enriched for CICs compared to non-enriched TC-1 cells. Following treatment with IFN-γ, both CIC enriched and non-enriched TC-1 cells expressed similar levels of MHC-I, and the increased MHC-I expression on CICs resulted in greater CTL-mediated tumor lysis and improved tumor-free survival in mice.

Conclusions

These results suggest that the attenuated expression of MHC-I molecules by CICs represents a potential strategy of CICs to escape immune recognition, and that the development of successful immunotherapy strategies targeting CICs may decrease their resistance to T cell-mediated immune detection by enhancing CIC MHC-I expression.

https://ift.tt/2JqZIgG

FOLFOX activity in a rare case of metastatic colonic adenocarcinoma of the tongue: a case report

Abstract

Background

Adenocarcinomas of the oral cavity are rare neoplasms, and only four cases of primary colonic adenocarcinoma of the tongue have ever been described in literature. Very few information about chemotherapy sensitiveness of this type of neoplasia is available, with only one regimen that showed some activity in a metastatic patient.

Case presentation

We describe the case of a patient bearing a metastatic colonic adenocarcinoma of the tongue submitted to a first-line chemotherapy with oxaliplatin, 5-fluorouracil and folinic acid (FOLFOX regimen). After chemotherapy the patient obtained the complete disappearance of the primitive neoplasia located in the body of the tongue, and a tumor size reduction > 50% of liver and lung metastases.

Conclusions

This case demonstrated the activity of the combination of oxaliplatin and 5-fluorouracil in this very rare neoplasia. The FOLFOX regimen might be considered either in advanced and especially in the neoadjuvant setting, when the reduction of the primary tumor is highly needed.

https://ift.tt/2HTr6XF

Complex phenotype of dyskeratosis congenita and mood dysregulation with novel homozygous RTEL1 and TPH1 variants

American Journal of Medical Genetics Part A, EarlyView.


https://ift.tt/2HONGka

Angelman syndrome in adolescence and adulthood: A retrospective chart review of 53 cases

American Journal of Medical Genetics Part A, EarlyView.


https://ift.tt/2vQ6QkS

Genetic correction of serum AFP level improves risk prediction of primary hepatocellular carcinoma in the Dongfeng–Tongji cohort study

Cancer Medicine, EarlyView.


https://ift.tt/2r2EtdH

Subjective and psychological well‐being in Parkinson's Disease: A systematic review

Acta Neurologica Scandinavica, EarlyView.


https://ift.tt/2r290Im

Long-Term Outcomes of the ADRENAL Trial

To the Editor: We recently reported the primary results of the Adjunctive Corticosteroid Treatment in Critically Ill Patients with Septic Shock (ADRENAL) trial, which tested the hypothesis that hydrocortisone would result in lower mortality than placebo among patients with septic shock. Further…

https://ift.tt/2Ff5jUZ

A review of the mechanisms of action of dimethylfumarate in the treatment of psoriasis

Experimental Dermatology, EarlyView.


https://ift.tt/2FhqKEY

Efficacy of single‐incision laparoscopic totally extraperitoneal repair for irreducible or incarcerated inguinal hernia

Asian Journal of Endoscopic Surgery, EarlyView.


https://ift.tt/2HsaKSl

Impact of clinical trial participation on survival in patients with castration-resistant prostate cancer: a multi-center analysis

Abstract

Background

Clinical trial (CT) participation may confer access to new, potentially active agents before their general availability. This study aimed to investigate the potential survival benefit of participation in investigational CTs of novel hormonal, chemotherapeutic, and radiopharmaceutical agents in patients with castration-resistant prostate cancer (CRPC).

Methods

This multi-center, retrospective analysis included 299 consecutive patients with newly diagnosed, non-metastatic or metastatic CRPC between September 2009 and March 2017. Of these, 65 (21.7%) patients participated in CTs pertaining to systemic treatment targeting CRPC and 234 (78.3%) patients received pre-established, standard systemic treatment outside of a CT setting. The survival advantage of CT participation regarding cancer-specific survival (CSS) was investigated.

Results

An Eastern Cooperative Oncology Group performance status (ECOG PS) ≥2 at CRPC diagnosis was found in a lower proportion CT participants than in non-participants (4.6% vs. 14.9%; p = 0.033). During the median follow-up period of 16.0 months, CT participants exhibited significantly higher 2-year CSS survival rates (61.3% vs. 42.4%; p = 0.003) than did non-participants. Multivariate analysis identified prostate-specific antigen and alkaline phosphatase levels at CRPC onset, Gleason score ≥ 8, ECOG PS ≥2, less number of docetaxel cycles administered, and non-participation in CTs as independent predictors for a lower risk of CSS.

Conclusions

Patients diagnosed with CRPC who participated in CTs exhibited longer CSS durations than non-participants who received pre-established, standard systemic therapy outside of a CT setting. Our findings imply that CT participation is associated with CSS, and that CT participation should be offered to patients with CRPC whenever indicated.

https://ift.tt/2HPfHYJ

Scaling‐up biofortified beans high in iron and zinc through the school‐feeding program: A sensory acceptance study with schoolchildren from two departments in southwest Colombia

Food Science &Nutrition, EarlyView.


https://ift.tt/2I2yEFi

Bevacizumab biosimilars: scientific justification for extrapolation of indications

Future Oncology, Ahead of Print.


https://ift.tt/2Ff9Zu1

Present role and future perspectives of interventional radiology in the treatment of painful bone lesions

Future Oncology, Ahead of Print.


https://ift.tt/2KgeE2j

Difference in prostate cancer incidence around sixty years: effects of age and metabolic diseases

Cancer Medicine, EarlyView.


https://ift.tt/2vMO123

Multicenter analysis of stereotactic radiotherapy of the resection cavity in patients with brain metastases

Cancer Medicine, EarlyView.


https://ift.tt/2qZMK2R

Amphotericin B suppresses M2 phenotypes and B7-H1 expression in macrophages to prevent Raji cell proliferation

Abstract

Background

Macrophages in the tumor microenvironment play a critical role in tumorigenesis and anti-cancer drug resistance. Burkitt's lymphoma (BL) is a B-cell non-Hodgkin's lymphoma with dense macrophage infiltration. However, the role for macrophages in BL remains largely unknown.

Methods

B7-H1, a transmembrane glycoprotein in the B7 family, suppresses T cell activation and proliferation and induces the apoptosis of activated T cells. The expression of B7-H1 in BL clinical tissues was determined by streptavidin-peroxidase immunohistochemistry. The mutual regulation between macrophages and BL Raji cells was investigated in a co-culture system. The cell proliferation and cell cycle distribution of Raji cells were determined using BrdU staining coupled with flow cytometry. CD163, CD204 and B7-H1 expression was assessed by flow cytometry and Western blot. Cell invasion was analyzed by Transwell assay. The expression of cytokines was detected by quantitative RT-PCR. Immunofluorescence and allogeneic T-cell proliferation assays were used to compare the expression of B7-H1, p-STAT6, or p-STAT3 and CD3+ T cell proliferation treated with or without amphotericin B.

Results

B7-H1 was highly expressed in tumor infiltration macrophages in most clinical BL tissues. In vitro, Raji cells synthesized IL-4, IL-6, IL-10 and IL-13 to induce CD163, CD204 and B7-H1 expression in co-cultured macrophages, which in turn promoted Raji cell proliferation and invasion. Interestingly, antifungal agent amphotericin B not only inhibited STAT6 phosphorylation to suppress the M2 polarization of macrophages, but also promoted CD3+ T cell proliferation by regulating B7-H1 protein expression in macrophages.

Conclusion

Amphotericin B might represent a novel immunotherapeutic approach to treat patients with BL.

https://ift.tt/2HYPiFt

Determination of the Stoichiometry between α- and γ1 Subunits of the BK Channel Using LRET

Two families of accessory proteins, β and γ, modulate BK channel gating and pharmacology. Notably, in the absence of internal Ca2+, the γ1 subunit promotes a large shift of the BK conductance-voltage curve to more negative potentials. However, very little is known about how α- and γ1 subunits interact. In particular, the association stoichiometry between both subunits is unknown. Here, we propose a method to answer this question using lanthanide resonance energy transfer. The method assumes that the kinetics of lanthanide resonance energy transfer-sensitized emission of the donor double-labeled α/γ1 complex is the linear combination of the kinetics of the sensitized emission in single-labeled complexes.

https://ift.tt/2Hrce3i

Multiple Arginine Residues Are Methylated in Drosophila Mre11 and Required for Survival Following Ionizing Radiation

Mre11 is a key player for DNA double strand break repair. Previous studies have shown that mammalian Mre11 is methylated at multiple arginines in its C-terminal Glycine-Arginine-Rich motif (GAR) by protein arginine methyltransferase PRMT1. Here, we found that the Drosophila Mre11 is methylated at arginines 559, 563, 565, and 569 in the GAR motif by DART1, the Drosophila homolog of PRMT1. Mre11 interacts with DART1 in S2 cells, and this interaction does not require the GAR motif. Arginines methylated Mre11 localizes exclusively in the nucleus as soluble nuclear protein or chromatin-binding protein. To study the in vivo functions of methylation, we generated the single Arg-Ala and all Arginines mutated flies. We found these mutants were sensitive to ionizing radiation. Furthermore, Arg-Ala mutated flies had no irradiation induced G2/M checkpoint defect in wing disc and eye disc. Thus, we provided evidence that arginines in Drosophila Mre11 are methylated by DART1 methytransferase and flies loss of arginine methylation are sensitive to irradiation.

https://ift.tt/2qZMUGE

Nerve growth factor‐dependent hyperexcitability of capsaicin‐sensitive bladder afferent neurones in mice with spinal cord injury

Experimental Physiology, EarlyView.


https://ift.tt/2qZSzNw

Suppression of TGFβ-mediated conversion of endothelial cells and fibroblasts into cancer associated (myo)fibroblasts via HDAC inhibition

Suppression of TGFβ-mediated conversion of endothelial cells and fibroblasts into cancer associated (myo)fibroblasts via HDAC inhibition

Suppression of TGFβ-mediated conversion of endothelial cells and fibroblasts into cancer associated (myo)fibroblasts via HDAC inhibition, Published online: 26 April 2018; doi:10.1038/s41416-018-0072-3

Suppression of TGFβ-mediated conversion of endothelial cells and fibroblasts into cancer associated (myo)fibroblasts via HDAC inhibition

https://ift.tt/2r0QOjh

Cutaneous neurofibromas in the genomics era: current understanding and open questions

Cutaneous neurofibromas in the genomics era: current understanding and open questions

Cutaneous neurofibromas in the genomics era: current understanding and open questions, Published online: 26 April 2018; doi:10.1038/s41416-018-0073-2

Cutaneous neurofibromas in the genomics era: current understanding and open questions

https://ift.tt/2Jspq4x

Phase I study of nab-paclitaxel, gemcitabine, and bevacizumab in patients with advanced cancers

Phase I study of nab-paclitaxel, gemcitabine, and bevacizumab in patients with advanced cancers

Phase I study of nab-paclitaxel, gemcitabine, and bevacizumab in patients with advanced cancers, Published online: 26 April 2018; doi:10.1038/s41416-018-0068-z

Phase I study of nab-paclitaxel, gemcitabine, and bevacizumab in patients with advanced cancers

https://ift.tt/2HSfu76

Differential expression of IL-6/IL-6R and MAO-A regulates invasion/angiogenesis in breast cancer

Differential expression of IL-6/IL-6R and MAO-A regulates invasion/angiogenesis in breast cancer

Differential expression of IL-6/IL-6R and MAO-A regulates invasion/angiogenesis in breast cancer, Published online: 26 April 2018; doi:10.1038/s41416-018-0078-x

Differential expression of IL-6/IL-6R and MAO-A regulates invasion/angiogenesis in breast cancer

https://ift.tt/2HSfiEU

Association between single-nucleotide polymorphisms and adverse events in nivolumab-treated non-small cell lung cancer patients

Association between single-nucleotide polymorphisms and adverse events in nivolumab-treated non-small cell lung cancer patients

Association between single-nucleotide polymorphisms and adverse events in nivolumab-treated non-small cell lung cancer patients, Published online: 26 April 2018; doi:10.1038/s41416-018-0074-1

Association between single-nucleotide polymorphisms and adverse events in nivolumab-treated non-small cell lung cancer patients

https://ift.tt/2JrQdxI

Systemic immune response induced by oxaliplatin-based neoadjuvant therapy favours survival without metastatic progression in high-risk rectal cancer

Systemic immune response induced by oxaliplatin-based neoadjuvant therapy favours survival without metastatic progression in high-risk rectal cancer

Systemic immune response induced by oxaliplatin-based neoadjuvant therapy favours survival without metastatic progression in high-risk rectal cancer, Published online: 26 April 2018; doi:10.1038/s41416-018-0085-y

Systemic immune response induced by oxaliplatin-based neoadjuvant therapy favours survival without metastatic progression in high-risk rectal cancer

https://ift.tt/2Jtug1x

Giant Brunner's gland adenoma of the duodenum manifested by melena

ANZ Journal of Surgery, EarlyView.


https://ift.tt/2KfHnEH

Gangrenous giant Meckel's diverticulitis masquerading acute appendicitis: a surgical conundrum

ANZ Journal of Surgery, EarlyView.


https://ift.tt/2Fh0eeU

Diverticulum formation from interposed colonic graft following oesophageal reconstruction

ANZ Journal of Surgery, EarlyView.


https://ift.tt/2Kgu2vZ

Importance of timing in staging head and neck cancer: cervical adenopathy post‐tonsillectomy mimicking malignancy

ANZ Journal of Surgery, EarlyView.


https://ift.tt/2HsMgwa

People With Opioid Use Disorder Have High Suicide Rate

WEDNESDAY, April 25, 2018 -- Patients with opioid use disorder (OUD) seem to have a high rate of suicide, according to a perspective piece published in the April 26 issue of the New England Journal of Medicine. Maria A. Oquendo, M.D., Ph.D., from...

https://ift.tt/2r0VQvs

Medicare Requiring Hospitals to Post Prices Online

WEDNESDAY, April 25, 2018 -- U.S. hospitals will have to post their standard prices online and make it easier for patients to access their electronic medical records, Medicare officials said Tuesday. Currently, hospitals must make their prices...

https://ift.tt/2Hrz2Qp

Restless Brain Syndrome Tied to Changes in the Brain

WEDNESDAY, April 25, 2018 -- Patients with restless legs syndrome (RLS) have morphologic changes in the brain, which could be responsible for the sensory functional symptoms of RLS, according to a study published online April 25 in...

https://ift.tt/2r1apPq

Risk of Adverse Birth Outcomes No Higher With TDF-FTC-LPV/r

WEDNESDAY, April 25, 2018 -- For HIV-infected women and their infants, the risk of adverse birth outcomes is similar with tenofovir, emtricitabine, and ritonavir-boosted lopinavir (TDF-FTC-LPV/r) compared with zidovudine, lamivudine, and...

https://ift.tt/2HwuB7a

Fetal Inflammation May Play Role in Preterm Labor

WEDNESDAY, April 25, 2018 -- Fetal inflammation and rejection of maternal antigens is associated with uterine contractility and aberrant fetal immune responses, which may play a role in preterm labor (PTL), according to a study published in the...

https://ift.tt/2r28dHD

A Case of Pyoderma Gangrenosum Misdiagnosed as Necrotizing Infection: A Potential Diagnostic Catastrophe

In this article, we present a case of pyoderma gangrenosum (PG), misdiagnosed initially as a necrotizing infection that significantly worsened due to repeated surgical debridement and aggressive wound care therapy, almost resulting in limb amputation despite antibiotic therapy. The PG lesions improved after pancytopenia were further investigated, and the diagnosis and treatment of an underlying hematologic malignancy was initiated. The diagnosis and management of PG is challenging given the paucity of robust clinical evidence, lack of standard diagnostic criteria, and absence of clinical practice guidelines. It is imperative that clinicians recognize PG as a clinical diagnosis that must be considered in any patient with enlarging, sterile, necrotic lesions that are unresponsive to prolonged and appropriate antibiotics. Early recognition can prevent devastating sequelae such as deep tissue and bone infections associated with a chronic open wound, severe cosmetic morbidity, and potential limb amputation.

https://ift.tt/2vMNqx5

Irreversible Electroporation in Patients with Pancreatic Cancer: How Important Is the New Weapon?

Background. Pancreatic cancer (PC) is a deadly disease with poor prognosis in the general population. We aimed to quantitate overall survival of patients with PC after irreversible electroporation (IRE) and the incidence of relevant complications. Methods. We performed a literature search via five electronic databases (PubMed, Embase, Web of Science, Scopus, and Cochrane Library databases) up to August 2017. The primary outcomes were overall survival and prognosis. Secondary outcomes included the response of post-IRE complications. Fixed-effects or random-effects meta-analysis was conducted to pool these data. Results. A total of 15 eligible articles involving 535 patients were included. The primary outcomes showed that the pooled prevalence estimates of overall survival were 94.1% (95% CI: 90.7–97.5), 80.9% (95% CI: 72.5–89.4), 54.5% (95% CI: 38.3–70.6), and 33.8% (95% CI: 14.2–53.5) at 3, 6, 12, and 24 months, and the pooled prevalence data of complete response (CR) at 2 months, partial response (PR) at 3 months, and progression at 3 months were 12.5% (95% CI: 2.9–22.2), 48.5% (95% CI: 39.4–57.6), and 19.7% (95% CI: 7.3–32.2), respectively. The secondary outcomes showed that the pooled prevalence values of post-IRE complications were abscess 6.6% (95% CI: 0.2–13), fistula 10.6% (95% CI: 2.5–18.7), pain 33.5% (95% CI: 14.5–52.5), infection 16.1% (95% CI: 3.9–28.4), thrombosis 4.9% (95% CI: 1.2–8.5), pancreatitis 7.2% (95% CI: 3.1–11.2), bleeding 4.2% (95% CI: −0.5–8.9), cholangitis 4.2% (95% CI: −0.5–8.9), nausea 9.6% (95% CI: 4.4–14.8), biliary obstruction 13.8% (95% CI: 4.2–23.3), chest tightness 7.6% (95% CI: 0.5–14.6), and hypoglycemia 5.9% (95% CI: −0.4–12.2). Conclusions. This meta-analysis indicated a clear survival benefit for PC patients who received irreversible electroporation therapy, although future safety and effectivity monitoring from more large-scale studies will be needed.

https://ift.tt/2FhUBNp

Predicting Acute Renal Injury in Cancer Patients Receiving Cisplatin Using Urinary Neutrophil Gelatinase‐Associated Lipocalin and Cystatin C

Clinical and Translational Science, EarlyView.


https://ift.tt/2r0Njsq

Model predicting the microvascular invasion and satellite lesions of hepatocelluar carcinoma after hepatectomy

ANZ Journal of Surgery, EarlyView.


https://ift.tt/2qZenJp

Blunt force abdominal trauma: a rare case of multiple splenic pseudocysts

ANZ Journal of Surgery, EarlyView.


https://ift.tt/2r50Z6D

Median nerve schwannoma

ANZ Journal of Surgery, EarlyView.


https://ift.tt/2vMetJ9

Inflammatory cell indexes as preoperative predictors of hospital stay in open elective thoracic surgery

ANZ Journal of Surgery, EarlyView.


https://ift.tt/2qUuS9x

CapsidMesh: Atomic‐detail structured mesh representation of icosahedral viral capsids and the study of their mechanical properties

International Journal for Numerical Methods in Biomedical Engineering, EarlyView.


https://ift.tt/2qZzV8N

Fulminant Emphysematous Pancreatitis

https://ift.tt/2vMh71t

Outcomes of Endoscopic Submucosal Dissection vs Esophagectomy for T1 Esophageal Squamous Cell Carcinoma in a Real-world Cohort

Esophagectomy is the standard treatment for early-stage esophageal squamous cell carcinoma (EESCC), but patients who undergo this procedure have high morbidity and mortality. Endoscopic submucosal dissection (ESD) is a less-invasive procedure for treatment of EESCC, but is considered risky because this tumor frequently metastasizes to the lymph nodes. We aimed to directly compare outcomes of patients with EESCC treated with ESD vs esophagectomy.

https://ift.tt/2qYltNZ

Rates of Hospital Readmission Among Medicare Beneficiaries With Gastrointestinal Bleeding Vary Based on Etiology and Comorbidities

Gastrointestinal bleeding results in significant morbidity, mortality, and healthcare costs in the United States. The Center for Medicare and Medicaid Services' payment reform programs assess quality and value based on rates of hospital readmission for patients with gastrointestinal bleeding, but they identify these patients using Medicare Severity Diagnosis Related Groups (MS-DRGs), which include many types of gastrointestinal bleeding and do not account for the clinical heterogeneity among these patients.

https://ift.tt/2vMbvEn

Evidence to Support Monitoring of Vedolizumab Trough Concentrations in Patients With Inflammatory Bowel Diseases

Trough concentrations of vedolizumab were found to correlate with clinical response in phase 3 studies of patients with ulcerative colitis (UC) or Crohn's disease (CD). Nevertheless, there are no solid data to support monitoring of vedolizumab trough concentrations in treated patients. We investigated the correlation between vedolizumab exposure and response in a real-world population and aimed to identify patient factors that affect exposure and response.

https://ift.tt/2HR547W

Clinical spectrum of KIAA2022 pathogenic variants in males: Case report of two boys with kiaa2022 pathogenic variants and review of the literature

American Journal of Medical Genetics Part A, EarlyView.


https://ift.tt/2HsJ1Fd

Transplantation of autologous esophageal mucosa to prevent stricture after circumferential endoscopic submucosal dissection of early esophageal cancer (with video)

Esophageal stricture is a common adverse event after endoscopic submucosal dissection (ESD) when it involves entire circumference of esophagus. We aimed to assess the effectiveness and safety of endoscopic transplantation of autologous esophageal mucosa in preventing stricture formation after circumferential ESD.

https://ift.tt/2qVCN5A

Drug-filled, 3-D printed dentures could fight off infections

Researchers have developed 3-D printed dentures filled with antifungal medication to better treat oral fungal infections.

https://ift.tt/2KhjfkO

Intraspecific variation in the information content of an ornament: why relative dewlap size signals bite force in some, but not all island populations of Anolis sagrei

Abstract

In many animals, male secondary sexual traits advertise reliable information on fighting capacity in a male-male context. The iconic sexual signaling device of anole lizards, the dewlap, has been extensively studied in this respect. For several territorial anole species (experiencing strong intrasexual selection), there is evidence for a positive association between dewlap size and bite capacity, which is an important determinant of combat outcome in lizards. Intriguingly, earlier studies did not find this expected correlation (relative dewlap size–relative bite force) in the highly territorial brown anole lizard, Anolis sagrei. We hypothesize that the dewlap size-bite force relationship can differ among populations of the same species due to interpopulation variation in the degree of male-male competition. In line with this thought, we expect dewlap size to serve as a reliable predictor of bite performance only in those populations where the level of intrasexual selection is high. To tackle this hypothesis, we examined the relationship between male dewlap size and bite force on the intraspecific level in Anolis sagrei, using an extensive dataset encompassing information from 17 island populations distributed throughout the Caribbean. First, we assessed and compared the relationship between both variables in the 17 populations under study. Second, we linked the relative dewlap size–bite force relationship within each population to variation in the degree of intrasexual selection among populations, using sexual size dimorphism (SSD) and dewlap display intensity as surrogate measures. Our results showed that absolute dewlap size is an excellent predictor of maximum bite force in nearly all Anolis sagrei populations. However, relative dewlap size is only an honest signal of bite performance in 4 out of the 17 populations. Surprisingly, the level of signal honesty did not correlate with the strength of intrasexual selection. We offer a number of conceptual and methodological explanations for this unexpected finding.

https://ift.tt/2HXJdco

Sequence, Structure, and Expression of Opsins in the Monochromatic Stomatopod Squilla empusa

Abstract

Most stomatopod crustaceans have complex retinas in their compound eyes, with up to 16 spectral types of photoreceptors, but members of the superfamily Squilloidea have much simpler retinas, thought to contain a single photoreceptor spectral class. In the Atlantic stomatopod Squilla empusa, microspectrophotometry shows that all photoreceptors absorb light maximally at 517 nm, indicating that a single visual pigment is present in all photoreceptors in the retina. However, six distinct, but partial, long wavelength sensitive (LWS) opsin transcripts, which encode the protein component of the visual pigment, have been previously isolated through RT-PCR. In order to investigate the spectral and functional differences among S. empusa's opsins, we used RT-PCR to complete the 3' end of sequences for five of the six expressed opsins. The extended sequences spanned from the first transmembrane helix (TM1) to the 3' end of the coding region. Using homology-based modeling, we predicted the three-dimensional structure of the amino acid translation of the S. empusa opsins. Based on these analyses, S. empusa LWS opsins share a high sequence identity in transmembrane regions and in amino acids within 15Å of the chromophore-binding lysine on transmembrane helix 7 (TM7), suggesting that these opsins produce spectrally similar visual pigments in agreement with previous results. However, we propose that these spectrally similar opsins differ functionally, as there are non-conservative amino acid substitutions found in intracellular loop 2 (ICL2) and TM5/ICL3, which are critical regions for G-protein binding, and substitutions in extracellular regions suggest different chromophore attachment affinities. In situ hybridization of two of the opsins (Se5 and Se6) revealed strong co-expression in all photoreceptors in both midband and peripheral regions of the retina as well as in selected ocular and cerebral ganglion neuropils. These data suggest expression of multiple opsins - likely spectrally identical, but functionally different - in multiple types of neuronal cells in S. empusa. This suggests that the multiple opsins characteristic of other stomatopod species may have similar functional specialization.

https://ift.tt/2I4BLMZ

Species Loss: Exploring Opportunities with Art-Science

Abstract

Human-induced global change has triggered the sixth major extinction event on earth with profound consequences for humans and other species. A scientifically literate public is necessary to find and implement approaches to prevent or slow species loss. Creating science-inspired art can increase public understanding of the current anthropogenic biodiversity crisis and help people connect emotionally to difficult concepts. In spite of the pressure to avoid advocacy and emotion, there is a rich history of scientists who make art, as well as art-science collaborations resulting in provocative work that engages public interest; however, such interdisciplinary partnerships can often be challenging to initiate and navigate. Here we explore the goals, impacts, cascading impacts and lessons learned from art-science collaborations, as well as ideas for collaborative projects. Using three case studies based on Harrower's scientific research into species interactions, we illustrate the importance of artists as a primary audience and the potential for a combination of art and science presentations to influence public understanding and concern related to species loss.

https://ift.tt/2FhalQS

So you want to share your science…. Connecting to the world of informal science learning

Abstract

Scientists can reap personal rewards through collaborations with science and natural history museums, zoos, botanical gardens, aquaria, parks, and nature preserves, and, while doing so, help to advance science literacy and broaden participation in the natural sciences. Beyond volunteer opportunities, which allow scientists to contribute their knowledge and passion within the context of existing programs and activities, there are also opportunities for scientists to bring their knowledge and resources to the design and implementation of new learning experiences for visitors to these informal science learning organizations (ISLOs). Well-designed education outreach plans that leverage the expertise and broad audiences of ISLOs can also enhance the prospects of research grant proposals made to agencies such as National Science Foundation, which encourage researchers to pay careful attention to the broader impacts of their research as well as its intellectual merit. Few scientists, however, have had the opportunity to become familiar with the pedagogy and design of informal or 'free-choice' science learning, and fewer still know how to go about the process of collaborating with ISLO's in developing and implementing effective programs, exhibits, and other learning experiences. This article, written by an experienced science museum professional, provides guidance for individual scientists and research groups interested in pursuing effective education outreach collaborations with science museums and other ISLOs. When prospective partners begin discussions early in the proposal development process, they increase the likelihood of successful outcomes in funding, implementation, and impact. A strategic planning worksheet is provided, along with a carefully-selected set of further resources to guide the design and planning of informal science learning experiences.

https://ift.tt/2HZZUUR

Unveiling Impact Identities: A Path for Connecting Science and Society

Abstract

We propose a thoughtful process for scientists to develop their "impact identity", a concept that integrates scholarship in a scientific discipline with societal needs, personal preferences, capacities and skills, and one's institutional context. Approaching broader impacts from a place of integrated identity can support cascading impacts that develop over the course of a career. We argue identity is a productive driver that can improve outcomes for scientists and for society. Widespread adoption of the concept of impact identity may also have implications for the recruitment and retention of a more diverse range of scientist.

https://ift.tt/2HX16bj

On the Cutting Edge of Research to Conserve At-Risk Species: Maximizing Impact through Partnerships

Abstract

Today's conservation challenges are complex. Solving these challenges often requires scientific collaborations that extend beyond the scope, expertise, and capacity of any single agency, organization, or institution. Conservation efforts can benefit from interdisciplinary collaboration, scientific and technological innovations, and the leveraging of capacity and resources among partners. Here we explore a series of case studies demonstrating how collaborative scientific partnerships are furthering the mission of the U.S. Fish and Wildlife Service, including: 1) contaminants of emerging concern in the Great Lakes Basin, 2) Poweshiek skipperling conservation, 3) using technology to improve population survey methods for bats and monarch butterfly, and 4) Big River restoration in the Southeast Missouri lead mining district. These case studies illustrate how strategic and effective scientific collaboration is a multi-stage process that requires investment of time and resources by all participants. Early coordination and communication is crucial to aligning planned work with scientific and decision-making needs. Collaborations between USFWS and external scientists can be mutually beneficial by supporting the agency mission while also providing an avenue for innovative research to be directly applied in conservation decisions and management actions.

https://ift.tt/2Fh67sr

High temperature, oxygen, and performance: Insights from reptiles and amphibians

Synopsis

Much recent theoretical and empirical work has sought to describe the physiological mechanisms underlying thermal tolerance in animals. Leading hypotheses can be broadly divided into two categories that primarily differ in organizational scale: 1) high temperature directly reduces the function of subcellular machinery, such as enzymes and cell membranes, or 2) high temperature disrupts system-level interactions, such as mismatches in the supply and demand of oxygen, prior to having any direct negative effect on the subcellular machinery. Nonetheless, a general framework describing the contexts under which either subcellular component or organ system failure limits organisms at high temperatures remains elusive. With this commentary, we leverage decades of research on the physiology of ectothermic tetrapods (amphibians and non-avian reptiles) to address these hypotheses. Available data suggest both mechanisms are important. Thus, we expand previous work and propose the Hierarchical Mechanisms of Thermal Limitation (HMTL) hypothesis, which explains how subcellular and organ system failures interact to limit performance and set tolerance limits at high temperatures. We further integrate this framework with the thermal performance curve paradigm commonly used to predict the effects of thermal environments on performance and fitness. The HMTL framework appears to successfully explain diverse observations in reptiles and amphibians and makes numerous predictions that remain untested. We hope that this framework spurs further research in diverse taxa and facilitates mechanistic forecasts of biological responses to climate change.

https://ift.tt/2HZLio9

Developing Interactive Exhibits with Scientists: Three Example Collaborations from the Life Sciences Collection at the Exploratorium

Abstract

Science museums have made a concerted effort to work with researchers to incorporate current scientific findings and practices into informal learning opportunities for museum visitors. Many of these efforts have focused on creating opportunities and support for researchers to interact face-to-face with the public through, for example, speaker series, community forums, and engineering competitions. However, there are other means by which practicing scientists can find a voice on the museum floor - through the design and development of exhibits. Here we describe how researchers and museum professionals have worked together to create innovative exhibit experiences for an interactive science museum. For each example: scientist as (1) data providers, (2) advisors, and (3) co-developers, we highlight essential components for a successful partnership and pitfalls to avoid when collaborating on museum exhibits. Not many museums prototype and build their own exhibits like the Exploratorium. In those cases, there may be similar opportunities in more mediated offerings such as public demonstrations or lectures or in other formats that allow for direct interactions between scientists and visitors.We believe there are many opportunities for researchers to share natural phenomena, to advise on exhibit development and interpretation, to provide much needed materials, and to otherwise incorporate authentic research into the learning experiences at museums, no matter what the format.

https://ift.tt/2HvnJmr

Celecoxib enhances the therapeutic efficacy of epirubicin for Novikoff hepatoma in rats

Cancer Medicine, EarlyView.


https://ift.tt/2vLREFs

Tissue‐based quantitative proteomics to screen and identify the potential biomarkers for early recurrence/metastasis of esophageal squamous cell carcinoma

Cancer Medicine, EarlyView.


https://ift.tt/2HNU5fv

Issue Information

Cancer Medicine, Volume 7, Issue 4, Page 941-942, April 2018.


https://ift.tt/2r5nTtN

Kuypers and Vanhove reply to ‘Was 4β‐hydroxycholesterol ever going to be a useful marker of CYP3A4 activity?’ by Neuhoff and Tucker

British Journal of Clinical Pharmacology, EarlyView.


https://ift.tt/2KgcIar

Themes addressed by couples with advanced cancer during a communication skills training intervention

Couple-based communication interventions have beneficial effects for patients with cancer and their partners. However, few studies have targeted patients with advanced stages of disease and little is known about how best to assist couples in discussing issues related to life-limiting illness.

https://ift.tt/2vP3vT8

Cutaneous neurofibromas in the genomics era: current understanding and open questions

https://ift.tt/2JoeFAk

Differential expression of IL-6/IL-6R and MAO-A regulates invasion/angiogenesis in breast cancer

https://ift.tt/2JrdIXW

Vinorelbine, cyclophosphamide and 5-FU effects on the circulating and intratumoural landscape of immune cells improve anti-PD-L1 efficacy in preclinical models of breast cancer and lymphoma

https://ift.tt/2HTxvSQ

Suppression of TGFβ-mediated conversion of endothelial cells and fibroblasts into cancer associated (myo)fibroblasts via HDAC inhibition

https://ift.tt/2r4Rfcz

Prediction of major complications after hepatectomy using liver stiffness values determined by magnetic resonance elastography

British Journal of Surgery, EarlyView.


https://ift.tt/2qYfnx7

Genetic And Morphological Evaluation (GAME) score for patients with colorectal liver metastases

British Journal of Surgery, EarlyView.


https://ift.tt/2qYfDfz

Population‐based study of mortality and major amputation following lower limb revascularization

British Journal of Surgery, EarlyView.


https://ift.tt/2vLYvPd

Gene expression profiles for a prognostic immunoscore in gastric cancer

British Journal of Surgery, EarlyView.


https://ift.tt/2HNRn9P

Reappraisal of classification of distal cholangiocarcinoma based on tumour depth

British Journal of Surgery, EarlyView.


https://ift.tt/2vS7RbY

Risk of recurrence and death in patients with breast cancer after delayed deep inferior epigastric perforator flap reconstruction

British Journal of Surgery, EarlyView.


https://ift.tt/2vLYEC8

Randomized clinical trial of elective resection versus observation in diverticulitis with extraluminal air or abscess initially managed conservatively

British Journal of Surgery, EarlyView.


https://ift.tt/2vJinTa

Glomeruloid hemangioma associated with TAFRO syndrome

Glomeruloid hemangioma is a rare cutaneous lesion which has been considered as a specific cutaneous marker of POEMS syndrome. Herein, we present the first case of glomeruloid hemangioma associated with TAFRO syndrome, a unique variant of idiopathic multicentric Castleman's disease (iMCD). The patient is a 74-year-old female presented with fever, cervical lymphadenopathy, thrombocytopenia, bilateral pleural effusions and ascites. Biopsy of the lymph node revealed MCD-like histology and bone marrow biopsy showed mild reticulin fibrosis, consistent with TAFRO syndrome.

https://ift.tt/2HKpiAj

Incidence and Impact of Pre-treatment Tumor Cavitation on Survival Outcomes of Stage III Squamous-Cell Lung Cancer Patients Treated with Radical Concurrent Chemoradiotherapy

Impact of tumor cavitation (TC) on outcomes of locally-advanced squamous-cell lung cancer (LA-SqCLC) patients undergoing to concurrent chemoradiotherapy (C-CRT) was assessed. A total of 789 stages IIIA/B SqCLC patients were analyzed with the primary end-point of overall survival (OS). The TC was incident in 95 (12%) patients, and its presence was associated with significantly poorer median OS durations independent of the other covariates (p<0.001).

https://ift.tt/2HWXztz

Lamictal (lamotrigine): Drug Safety Communication - Serious Immune System Reaction

[Posted 04/25/2018] AUDIENCE: Health Professional, Patient, Pharmacy ISSUE: The FDA is warning that the medicine Lamictal (lamotrigine) for seizures and bipolar disorder can cause a rare but very serious reaction that excessively activates the...

https://ift.tt/2vLoWED

A Link Between Alzheimer's and Type II Diabetes Mellitus? Ca+2‐Mediated Signal Control and Protein Localization

BioEssays, EarlyView.


https://ift.tt/2vLQDgJ

Non‐Cell Cycle Functions of the CDK Network in Ciliogenesis: Recycling the Cell Cycle Oscillator

BioEssays, EarlyView.


https://ift.tt/2qZoFcx

Novel Channels of the Outer Membrane of Mitochondria: Recent Discoveries Change Our View

BioEssays, EarlyView.


https://ift.tt/2vLMzwL

Environmental or Nasal Cannula Supplemental Oxygen for Preterm Infants: A Randomized Cross-Over Trial

To test the hypothesis that environmental compared with nasal cannula oxygen decreases episodes of intermittent hypoxemia (oxygen saturations <85% for ≥10 seconds) in preterm infants on supplemental oxygen by providing a more stable hypopharyngeal oxygen concentration.

https://ift.tt/2Fgf7y3

Multi-Stakeholder Informed Guidelines for Direct Admission of Children to Hospital

To develop pediatric direct admission guidelines and prioritize outcomes to evaluate the safety and effectiveness of hospital admission processes.

https://ift.tt/2FgXuOk

A Brain Marker for Developmental Speech Disorders

To characterize the organization of speech- and language-related white matter tracts in children with developmental speech and/or language disorders.

https://ift.tt/2HvhPlg

Relationship between Epigenetic Maturity and Respiratory Morbidity in Preterm Infants

To assess associations between epigenetic maturity of extremely preterm babies (born at less than 28 weeks of gestation), neonatal interventions, and respiratory outcomes, including the administration of surfactant and postnatal corticosteroids, duration of assisted ventilation, and development of bronchopulmonary dysplasia (BPD).

https://ift.tt/2I16aeT

Loose Anagen Hair Syndrome

A 6-year-old white girl with blonde hair presented to the dermatology clinic with a 6-month history of hair that would not grow longer than her jaw line. Examination revealed thin blonde hair extending to the nape of the neck. The hair on the posterior scalp was unruly with waves and there were no specific patches of alopecia. She was bald until 2.5 years of age. Family history was negative for a similar disorder. Hair pull test revealed painless removal of >40 hairs. Microscopic evaluation of hairs revealed a majority of anagen hairs with a ruffled proximal cuticle and misshapen hair bulbs.

https://ift.tt/2Fgf31h

Parental Perspectives Regarding Outcomes of Very Preterm Infants: Toward a Balanced Approach

To explore parental perspectives regarding their preterm child at 18 months corrected age and to investigate whether reported answers correlate with level of neurodevelopmental impairment (NDI) as defined by clinicians. We hypothesized that parents would report more negative concerns with increasing level of NDI.

https://ift.tt/2HZRjBz

Review of Interventions and Radiation Exposure from Chest Computed Tomography in Children with Blunt Trauma

To determine the radiation risk to a child undergoing trauma evaluation with chest computed tomography (CCT) for every clinically actionable injury identified.

https://ift.tt/2HZRmgJ

Suction Mask vs Conventional Mask Ventilation in Term and Near-Term Infants in the Delivery Room: A Randomized Controlled Trial

To compare the suction mask, a new facemask that uses suction to create a seal between the mask and the infant's face, with a conventional soft, round silicone mask during positive pressure ventilation (PPV) in the delivery room in newborn infants >34 weeks of gestation.

https://ift.tt/2HZRpsV

As you like it: How the same data can support manifold views of overdiagnosis in breast cancer screening

International Journal of Cancer, EarlyView.


https://ift.tt/2HrWPj5

Regulatory T cells in autoimmune skin diseases

Experimental Dermatology, EarlyView.


https://ift.tt/2qYuKEY

Potentially inappropriate medication use in older patients with breast and colorectal cancer

Cancer, EarlyView.


https://ift.tt/2KeimJZ

Role of metastasis‐directed treatment in kidney cancer

Cancer, EarlyView.


https://ift.tt/2FgU3aK

Where there is smoke, there is not always fire

Cancer, EarlyView.


https://ift.tt/2Keimtt

Implications of false‐positive results for future cancer screenings

Cancer, EarlyView.


https://ift.tt/2Fh0rhW

Ribosome display and selection of single‐chain variable fragments effectively inhibit growth and progression of microspheres in vitro and in vivo

Cancer Science, EarlyView.


https://ift.tt/2HP5lZ6

Downregulation of miR‐491‐5p promotes gastric cancer metastasis by regulating SNAIL and FGFR4

Cancer Science, EarlyView.


https://ift.tt/2JnleTq

Long non‐coding RNA metastasis‐associated lung adenocarcinoma transcript 1 promotes lung adenocarcinoma by directly interacting with specificity protein 1

Cancer Science, EarlyView.


https://ift.tt/2HPV7aM

Development of a vaccine based on bacteria‐mimicking tumor cells coated with novel engineered toll‐like receptor 2 ligands

Cancer Science, EarlyView.


https://ift.tt/2Jo6eF5

Tunable Molecular‐Scale Materials for Catalyzing the Low‐Overpotential Electrochemical Conversion of CO2

Advanced Materials, EarlyView.


https://ift.tt/2HYG64b

Bioinspired Synthesis of Monolithic and Layered Aerogels

Advanced Materials, EarlyView.


https://ift.tt/2FetzXj

3D Printed Functional and Biological Materials on Moving Freeform Surfaces

Advanced Materials, EarlyView.


https://ift.tt/2HXzEKw

Semiconductive Single Molecular Bilayers Realized Using Geometrical Frustration

Advanced Materials, EarlyView.


https://ift.tt/2HwgiuX

Paintable and Rapidly Bondable Conductive Hydrogels as Therapeutic Cardiac Patches

Advanced Materials, EarlyView.


https://ift.tt/2JuwqxY

Synthesis of 2D Metal Chalcogenide Thin Films through the Process Involving Solution‐Phase Deposition

Advanced Materials, EarlyView.


https://ift.tt/2qY1UFx

Highly Efficient Photocatalytic Hydrogen Evolution by ReS2 via a Two‐Electron Catalytic Reaction

Advanced Materials, EarlyView.


https://ift.tt/2HtPZWl

Low‐Saturation‐Intensity, High‐Photostability, and High‐Resolution STED Nanoscopy Assisted by CsPbBr3 Quantum Dots

Advanced Materials, EarlyView.


https://ift.tt/2HSdSuf

Mechanochemical‐Assisted Synthesis of High‐Entropy Metal Nitride via a Soft Urea Strategy

Advanced Materials, EarlyView.


https://ift.tt/2Jo4ko0

Azo Compounds Derived from Electrochemical Reduction of Nitro Compounds for High Performance Li‐Ion Batteries

Advanced Materials, EarlyView.


https://ift.tt/2HZR49x

Ultrafast Single‐Band Upconversion Luminescence in a Liquid‐Quenched Amorphous Matrix

Advanced Materials, EarlyView.


https://ift.tt/2Fgy2sB

High Rate Production of Clean Water Based on the Combined Photo‐Electro‐Thermal Effect of Graphene Architecture

Advanced Materials, EarlyView.


https://ift.tt/2HXsNRn

Light‐Driven Reversible Transformation between Self‐Organized Simple Cubic Lattice and Helical Superstructure Enabled by a Molecular Switch Functionalized Nanocage

Advanced Materials, EarlyView.


https://ift.tt/2HwKUwB

Mechanobiological Mimicry of Helper T Lymphocytes to Evaluate Cell–Biomaterials Crosstalk

Advanced Materials, EarlyView.


https://ift.tt/2I040ME

Manipulation of Colloidal Particles in Three Dimensions via Microfluid Engineering

Advanced Materials, EarlyView.


https://ift.tt/2FgfecQ

A Novel Evaluation Index for Predicting the Degradation Rate of Frying Oils Based on Their Fatty Acid Composition

European Journal of Lipid Science and Technology, EarlyView.


https://ift.tt/2HrrFbM

Supplementing Grazing Dairy Ewes with Plant‐Derived Oil and Rumen‐Protected EPA+DHA Pellets Enhances Health‐Beneficial n−3 Long‐Chain Polyunsaturated Fatty Acids in Sheep Milk

European Journal of Lipid Science and Technology, EarlyView.


https://ift.tt/2r5cgD9

Effects of Calcium Content and Homogenization Method on the Microstructure, Rheology, and Stability of Emulsions Prepared with Soybean Flour Dispersions

European Journal of Lipid Science and Technology, EarlyView.


https://ift.tt/2HrrrkW

Facile Enzymatic Synthesis of Phosphatidylthreonine Using an Engineered Phospholipase D

European Journal of Lipid Science and Technology, EarlyView.


https://ift.tt/2r0wMVo

Effect of the Harvesting Time on the Quality of Olive Oils Produced in Calabria

European Journal of Lipid Science and Technology, EarlyView.


https://ift.tt/2Hrri0S

DHA‐Enriched Phosphatidylcholine and DHA‐Enriched Phosphatidylserine Improve Age‐Related Lipid Metabolic Disorder through Different Metabolism in the Senescence‐Accelerated Mouse

European Journal of Lipid Science and Technology, EarlyView.


https://ift.tt/2qZEgYM

Why Tyrosol Derivatives Have to Be Quantified in the Calculation of “Olive Oil Polyphenols” Content to Support the Health Claim Provisioned in the EC Reg. 432/2012

European Journal of Lipid Science and Technology, EarlyView.


https://ift.tt/2Hrr6ia

Identification of 4 novel mutations of androgen receptor gene in 8 Chinese families with complete androgen insensitivity syndrome

Clinical Genetics, EarlyView.


https://ift.tt/2KeI1SF

Single, short in‐del, and copy number variations detection in monogenic dyslipidemia using a next‐generation sequencing strategy

Clinical Genetics, EarlyView.


https://ift.tt/2FhuO83

Is mepivacaine as effective as lidocaine during inferior alveolar nerve blocks in patients with symptomatic irreversible pulpitis? A systematic review and meta‐analysis

International Endodontic Journal, EarlyView.


https://ift.tt/2FhufuX

Efficacy of chlorhexidine as a final irrigant in one‐visit root canal treatment: a prospective comparative study

International Endodontic Journal, EarlyView.


https://ift.tt/2Kayvjv

Outcomes of Patients With Syncope and Suspected Dementia

Academic Emergency Medicine, EarlyView.


https://ift.tt/2FeAU97

Erratum: fetal growth and premature delivery in pregnant women on antiepileptic drugs

Annals of Neurology, Volume 83, Issue 4, Page 872-872, April 2018.


https://ift.tt/2HsGUkQ

Stem cell modeling of mitochondrial parkinsonism reveals key functions of OPA1

Annals of Neurology, EarlyView.


https://ift.tt/2qZloZK

Even when right is all that's left: There are still more options for recovery from aphasia

Annals of Neurology, Volume 83, Issue 4, Page 661-663, April 2018.


https://ift.tt/2r0JLpN

Issue Information ‐ TOC

Annals of Neurology, Volume 83, Issue 4, April 2018.


https://ift.tt/2Hqcz6p

Developmental conduction aphasia after neonatal stroke

Annals of Neurology, Volume 83, Issue 4, Page 664-675, April 2018.


https://ift.tt/2r0oBs6

Genetic predisposition in anti‐LGI1 and anti‐NMDA receptor encephalitis

Annals of Neurology, Volume 83, Issue 4, Page 863-869, April 2018.


https://ift.tt/2HqcpvP

Issue Information ‐ Copyright

Annals of Neurology, Volume 83, Issue 4, April 2018.


https://ift.tt/2r2dbDY

Issue Information ‐ Masthead

Annals of Neurology, Volume 83, Issue 4, April 2018.


https://ift.tt/2HsVbhe

Annals of Neurology: Volume 83, Number 4, April 2018

Annals of Neurology, Volume 83, Issue 4, April 2018.


https://ift.tt/2r1HGdv

In vitro evaluation of 225Ac‐DOTA‐substance P for targeted alpha therapy of glioblastoma multiforme

Chemical Biology &Drug Design, EarlyView.


https://ift.tt/2HTuXUN

Antibacterial activity and in vivo wound healing potential of phenolic extracts from jaboticaba skin

Chemical Biology &Drug Design, EarlyView.


https://ift.tt/2HsyC8h

Different as night and day: Patterns of isolated seizures, clusters, and status epilepticus

Epilepsia, EarlyView.


https://ift.tt/2qYR6r1

Lamictal (lamotrigine): Drug Safety Communication - Serious Immune System Reaction

[Posted 04/25/2018] AUDIENCE: Health Professional, Patient, Pharmacy ISSUE: The FDA is warning that the medicine Lamictal (lamotrigine) for seizures and bipolar disorder can cause a rare but very serious reaction that excessively activates the...

https://ift.tt/2vLoWED

NREMT launches EMS certification app

The iPhone app allows EMS personnel to manage their continuing education and recertification components

https://ift.tt/2HJVELx

Endostar, a Modified Endostatin Induces Vascular Normalization to Improve Chemotherapy Efficacy through Suppression of Src Signaling Pathway

Cancer Biotherapy and Radiopharmaceuticals, Ahead of Print.


https://ift.tt/2KfVAS2

Development and Validation of RAPID: A Patient-Specific Monte Carlo Three-Dimensional Internal Dosimetry Platform

Cancer Biotherapy and Radiopharmaceuticals, Ahead of Print.


https://ift.tt/2Hsy7ev

What is the cause of drooling?

A person usually drools while asleep, when they have less control over their mouth. Infections, neurological conditions, and other issues can lead to more frequent drooling. We describe tools, tips, and medications that can reduce or eliminate this symptom. We also explore causes and complications. Learn more here.

https://ift.tt/2Htw7Tf

Desthiobiotin-Streptavidin-Affinity Mediated Purification of RNA-Interacting Proteins in Mesothelioma Cells

Desthiobiotin labeling of a synthetic 25-nucleotide RNA oligo, which contains an adenine-rich element (ARE) motif, allows specific binding of cytosolic ARE-binding protein.

https://ift.tt/2HtDZEh

Disagreement Seen Over Barriers to Kids' Daily Use of Asthma Meds

WEDNESDAY, April 25, 2018 -- Children, caregivers, and physicians report different barriers to daily use of asthma medications, according to a study published recently in the Journal of Asthma. Carolyn M. Arnold, M.P.H., from Johns Hopkins...

https://ift.tt/2HRBoHQ

Aortic Stiffness, Concentric LV Remodeling Linked in T2DM

WEDNESDAY, April 25, 2018 -- For patients with type 2 diabetes, aortic stiffness is associated with concentric left ventricular (LV) remodeling, according to a study published online April 16 in Diabetes. Gaurav S. Gulsin, M.B.Ch.B., from the...

https://ift.tt/2vGI2M2

IBD Associated With Increased Incidence of Parkinson's Disease

WEDNESDAY, April 25, 2018 -- Patients with inflammatory bowel disease (IBD) have increased incidence of Parkinson's disease (PD), which is attenuated with anti-tumor necrosis factor (TNF) therapy, according to a study published online April 23 in...

https://ift.tt/2qYgq0h

Increase in HTN in Children Based on 2017 AAP Guidelines

WEDNESDAY, April 25, 2018 -- The prevalence and severity of high blood pressure (BP) in children have increased based on the 2017 American Academy of Pediatrics clinical practice guidelines, according to a study published online April 23 in JAMA...

https://ift.tt/2vNnilO

About 40 Percent of Men Report Experiencing Weight Stigma

WEDNESDAY, April 25, 2018 -- A substantial proportion of men report experiencing weight stigma, according to a study published online April 23 in Obesity. Mary S. Himmelstein, Ph.D., from the University of Connecticut in Hartford, and colleagues...

https://ift.tt/2HRBjnw

Lupus Is a Leading Cause of Death in Young Women

WEDNESDAY, April 25, 2018 -- Systemic lupus erythematous (SLE) is among the top 20 leading causes of death in females between the ages of 5 and 64 years in the United States, according to a study published online April 18 in Arthritis &...

https://ift.tt/2vNnfGE

Factors ID'd for Hearing Loss After Loud Music Exposure

WEDNESDAY, April 25, 2018 -- Non-use of earplugs, use of alcohol and drugs, and male sex are associated with a temporary threshold shift (TTS) after music exposure at an outdoor music festival, according to a study published online April 19 in JAMA...

https://ift.tt/2qYi6qr

Lonafarnib May Lower Mortality in Hutchinson-Gilford Progeria

WEDNESDAY, April 25, 2018 -- Lonafarnib monotherapy is associated with lower mortality among patients with Hutchinson-Gilford progeria syndrome (HGPS), according to a study published in the April 24 issue of the Journal of the American Medical...

https://ift.tt/2vMWGRV

CDC: Birth Rate for 10- to-14-Year-Olds at Record Low in 2016

WEDNESDAY, April 25, 2018 -- From 2000 to 2016 there was a decrease in the birth rate for U.S. females aged 10 to 14 years, according to an April data brief published by the U.S. Centers for Disease Control and Prevention's National Center for...

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Alcohol Consumption Has Moderate Association With PMS

WEDNESDAY, April 25, 2018 -- Alcohol intake may be linked to the risk of premenstrual syndrome (PMS), according to a review published online April 23 in BMJ Open. María del Mar Fernández, from the University of Santiago de Compostela in Spain, and...

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Evidence for altered dendritic spine compartmentalization in Alzheimer’s disease and functional effects in a mouse model

Abstract

Alzheimer's disease (AD) is associated with a progressive loss of synapses and neurons. Studies in animal models indicate that morphological alterations of dendritic spines precede synapse loss, increasing the proportion of large and short ("stubby") spines. Whether similar alterations occur in human patients, and what their functional consequences could be, is not known. We analyzed biopsies from AD patients and APP x presenilin 1 knock-in mice that were previously shown to present a loss of pyramidal neurons in the CA1 area of the hippocampus. We observed that the proportion of stubby spines and the width of spine necks are inversely correlated with synapse density in frontal cortical biopsies from non-AD and AD patients. In mice, the reduction in the density of synapses in the stratum radiatum was preceded by an alteration of spine morphology, with a reduction of their length and an enlargement of their neck. Serial sectioning examined with electron microscopy allowed us to precisely measure spine parameters. Mathematical modeling indicated that the shortening and widening of the necks should alter the electrical compartmentalization of the spines, leading to reduced postsynaptic potentials in spine heads, but not in soma. Accordingly, there was no alteration in basal synaptic transmission, but long-term potentiation and spatial memory were impaired. These results indicate that an alteration of spine morphology could be involved in the early cognitive deficits associated with AD.

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Recent progress in perioperative management of patients undergoing esophagectomy for esophageal cancer

Abstract

Esophagectomy remains the mainstay of curative intent treatment for esophageal cancer. Oncologic esophagectomy is a highly invasive surgery and both morbidity and mortality rates still remain high. Recently, it has been revealed that multidisciplinary perioperative management can decrease the postoperative complications after esophagectomy. In this review, we summarized the recent progress in each component of multidisciplinary perioperative care bundle, including oral hygiene, cessation of smoking and alcohol, respiratory training, measurement of physical fitness, swallowing evaluation and rehabilitation, nutritional support, pain control and management of delirium. The accumulation of evidence and the popularization of knowledge will increase safety of esophagectomy and thus improve the outcome of patients with esophageal cancer.

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Cost-effectiveness and budget impact analyses of a colorectal cancer screening programme in a high adenoma prevalence scenario using MISCAN-Colon microsimulation model

Abstract

Background

The Basque Colorectal Cancer Screening Programme began in 2009 and the implementation has been complete since 2013. Faecal immunological testing was used for screening in individuals between 50 and 69 years old. Colorectal Cancer in Basque country is characterized by unusual epidemiological features given that Colorectal Cancer incidence is similar to other European countries while adenoma prevalence is higher. The object of our study was to economically evaluate the programme via cost-effectiveness and budget impact analyses with microsimulation models.

Methods

We applied the Microsimulation Screening Analysis (MISCAN)-Colon model to predict trends in Colorectal Cancer incidence and mortality and to quantify the short- and long-term effects and costs of the Basque Colorectal Cancer Screening Programme. The model was calibrated to the Basque demographics in 2008 and age-specific Colorectal Cancer incidence data in the Basque Cancer Registry from 2005 to 2008 before the screening begun. The model was also calibrated to the high adenoma prevalence observed for the Basque population in a previously published study. The multi-cohort approach used in the model included all the cohorts in the programme during 30 years of implementation, with lifetime follow-up. Unit costs were obtained from the Basque Health Service and both cost-effectiveness analysis and budget impact analysis were carried out.

Results

The goodness-of-fit of the model adaptation to observed programme data was evidence of validation. In the cost-effectiveness analysis, the savings from treatment were larger than the added costs due to screening. Thus, the Basque programme was dominant compared to no screening, as life expectancy increased by 29.3 days per person. The savings in the budget analysis appeared 10 years after the complete implementation of the programme. The average annual budget was €73.4 million from year 2023 onwards.

Conclusions

This economic evaluation showed a screening intervention with a major health gain that also produced net savings when a long follow-up was used to capture the late economic benefit. The number of colonoscopies required was high but remain within the capacity of the Basque Health Service. So far in Europe, no other population Colorectal Cancer screening programme has been evaluated by budget impact analysis.

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Visualization of Cellular Electrical Activity in Zebrafish Early Embryos and Tumors

Here, we show the process of creating a cellular electric voltage reporter zebrafish line to visualize embryonic development, movement, and fish tumor cells in vivo.

https://ift.tt/2qYN0hH

RapidDeploy becomes first Computer-Aided Dispatch (CAD) System to receive ProQA Titanium Certification

Priority Dispatch recognizes RapidDeploy for its dynamic, customizable interface and commitment to the public safety community.

https://ift.tt/2K9Badr

Attention demands of postural control in non-specific chronic low back pain subjects with low and high pain-related anxiety

Abstract

Impaired postural control in chronic low back pain (CLBP) has been attributed to deficits in sensory and motor functions. However, it is not known if pain-related anxiety affects motor and cognitive function of postural control. The aim of this study was to compare the interactive effects of postural and cognitive function in CLBP patients with high and low pain-related anxiety and healthy subjects. Thirty-eight patients with nonspecific CLBP (19 with low and 19 with high pain-related anxiety levels) and 20 asymptomatic subjects participated. Postural control was assessed by center of pressure (COP) parameters including mean total sway velocity, area, anterior–posterior (A–P), and medial–lateral (Med–Lat) range. Postural task was assessed during four conditions (eyes open with and without ankle vibration—eyes closed with and without ankle vibrations). Participants performed the postural task with or without auditory Stroop task. Average reaction time and error ratio of auditory Stroop test were calculated as measures of the cognitive task performance. Significantly reduced sway area was observed in CLBP patients with high pain-related anxiety and control subjects during the dual-task condition as compared with the single task. In addition, A–P range was significantly reduced in CLBP patients with high pain-related anxiety during dual tasking when eyes were closed with ankle vibration. In addition, only the CLBP subjects with high pain-related anxiety showed significantly longer reaction times by increasing the difficulty of standing postural task. Pain-related anxiety may influence the postural cognitive interactions in CLBP patients. Furthermore, it may be considered as a contributing factor for postural strategies adopted by CLBP patients.

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Recalibration of vocal affect by a dynamic face

Abstract

Perception of vocal affect is influenced by the concurrent sight of an emotional face. We demonstrate that the sight of an emotional face also can induce recalibration of vocal affect. Participants were exposed to videos of a 'happy' or 'fearful' face in combination with a slightly incongruous sentence with ambiguous prosody. After this exposure, ambiguous test sentences were rated as more 'happy' when the exposure phase contained 'happy' instead of 'fearful' faces. This auditory shift likely reflects recalibration that is induced by error minimization of the inter-sensory discrepancy. In line with this view, when the prosody of the exposure sentence was non-ambiguous and congruent with the face (without audiovisual discrepancy), aftereffects went in the opposite direction, likely reflecting adaptation. Our results demonstrate, for the first time, that perception of vocal affect is flexible and can be recalibrated by slightly discrepant visual information.

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The effects of audiovisual distraction on the muscle sympathetic responses to experimental muscle pain

Abstract

Pain elicited by intramuscular infusion of hypertonic saline solution causes muscle sympathetic nerve activity (MSNA) to increase in some subjects, yet decrease in others. Although the direction of the response is not predictable based on baseline physiological and psychological parameters, we know that it results from sustained functional changes in specific brain regions that are responsible for the behavioral and cardiovascular responses to psychological stressors, as well as those involved in attention. The aim of this study was to investigate whether MSNA responses to experimental muscle pain in humans could be altered with an audiovisual stimulus that served to distract them from the pain. MSNA was recorded from the left common peroneal nerve of 20 young healthy individuals during a 45-min intramuscular infusion of hypertonic saline solution into the ipsilateral tibialis anterior muscle. The distracting stimulus commenced 15 min after the start of the infusion and lasted for 15 min. Fifteen subjects showed an increase in mean burst amplitude of MSNA (to 176.4 ± 7.9% of baseline), while five showed a decrease (to 73.1 ± 5.2% of baseline); distraction had no effect on these profiles. These results indicate that even though the subjects were attending to the audiovisual stimulus, and were presumably distracted from the pain, it failed to alter the MSNA responses to muscle pain.

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Abdominal manifestations of IgG4-related disease: a pictorial review

Abstract

In the last decade, autoimmune pancreatitis has become recognised as part of a wider spectrum of IgG4-related disease, typically associated with elevated serum IgG4 levels and demonstrating a response to corticosteroid therapy. Radiologically, there is imaging overlap with other benign and neoplastic conditions. This pictorial review discusses the intra-abdominal manifestations of this disease on cross-sectional imaging before and after steroid treatment and the main radiological features which help to distinguish it from other key differentials.

Teaching Points

• Autoimmune pancreatitis is part of a spectrum of IgG4-related disease.

• Diagnosis is based on raised serum IgG4, clinical, radiological and histopathological findings.

• Cross-sectional imaging can demonstrate the typical findings of abdominal IgG4-related disease.

• Cross-sectional imaging can be used to monitor response to corticosteroid treatment.

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Quantification of amino acids and peptides in an ionic liquid based aqueous two-phase system by LC–MS analysis

Aqueous two-phase systems (ATPS) occur by the mixture of two polymers or a polymer and an inorganic salt in water. It was shown that not only polymers but also ionic liquids in combination with inorganic cosmo...

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Freiburg Neuropathology Case Conference

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Anal cytological lesions and HPV infection in individuals at increased risk for anal cancer

Cancer Cytopathology, EarlyView.


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Strategies for teaching effective communication skills

Cancer Cytopathology, EarlyView.


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Targeting of NF-{kappa}B to Dendritic Spines Is Required for Synaptic Signaling and Spine Development

Long-term forms of brain plasticity share a requirement for changes in gene expression induced by neuronal activity. Mechanisms that determine how the distinct and overlapping functions of multiple activity-responsive transcription factors, including nuclear factor B (NF-B), give rise to stimulus-appropriate neuronal responses remain unclear. We report that the p65/RelA subunit of NF-B confers subcellular enrichment at neuronal dendritic spines and engineer a p65 mutant that lacks spine enrichment (p65SE) but retains inherent transcriptional activity equivalent to wild-type p65. Wild-type p65 or p65SE both rescue NF-B-dependent gene expression in p65-deficient murine hippocampal neurons responding to diffuse (PMA/ionomycin) stimulation. In contrast, neurons lacking spine-enriched NF-B are selectively impaired in NF-B-dependent gene expression induced by elevated excitatory synaptic stimulation (bicuculline or glycine). We used the setting of excitatory synaptic activity during development that produces NF-B-dependent growth of dendritic spines to test physiological function of spine-enriched NF-B in an activity-dependent response. Expression of wild-type p65, but not p65SE, is capable of rescuing spine density to normal levels in p65-deficient pyramidal neurons. Collectively, these data reveal that spatial localization in dendritic spines contributes unique capacities to the NF-B transcription factor in synaptic activity-dependent responses.

SIGNIFICANCE STATEMENT Extensive research has established a model in which the regulation of neuronal gene expression enables enduring forms of plasticity and learning. However, mechanisms imparting stimulus specificity to gene regulation, ensuring biologically appropriate responses, remain incompletely understood. NF-B is a potent transcription factor with evolutionarily conserved functions in learning and the growth of excitatory synaptic contacts. Neuronal NF-B is localized in both synapse and somatic compartments, but whether the synaptic pool of NF-B has discrete functions is unknown. This study reveals that NF-B enriched in dendritic spines (the postsynaptic sites of excitatory contacts) is selectively required for NF-B activation by synaptic stimulation and normal dendritic spine development. These results support spatial localization at synapses as a key variable mediating selective stimulus–response coupling.

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Cell-Type-Specific Shank2 Deletion in Mice Leads to Differential Synaptic and Behavioral Phenotypes

Shank2 is an excitatory postsynaptic scaffolding protein implicated in synaptic regulation and psychiatric disorders including autism spectrum disorders. Conventional Shank2-mutant (Shank2^–/–) mice display several autistic-like behaviors, including social deficits, repetitive behaviors, hyperactivity, and anxiety-like behaviors. However, cell-type-specific contributions to these behaviors have remained largely unclear. Here, we deleted Shank2 in specific cell types and found that male mice lacking Shank2 in excitatory neurons (CaMKII-Cre;Shank2^fl/fl) show social interaction deficits and mild social communication deficits, hyperactivity, and anxiety-like behaviors. In particular, male mice lacking Shank2 in GABAergic inhibitory neurons (Viaat-Cre;Shank2^fl/fl) display social communication deficits, repetitive self-grooming, and mild hyperactivity. These behavioral changes were associated with distinct changes in hippocampal and striatal synaptic transmission in the two mouse lines. These results indicate that cell-type-specific deletions of Shank2 in mice lead to differential synaptic and behavioral abnormalities.

SIGNIFICANCE STATEMENT Shank2 is an abundant excitatory postsynaptic scaffolding protein implicated in the regulation of excitatory synapses and diverse psychiatric disorders including autism spectrum disorders. Previous studies have reported in vivo functions of Shank2 mainly using global Shank2-null mice, but it remains largely unclear how individual cell types contribute to Shank2-dependent regulation of neuronal synapses and behaviors. Here, we have characterized conditional Shank2-mutant mice carrying the Shank2 deletion in excitatory and inhibitory neurons. These mouse lines display distinct alterations of synaptic transmission in the hippocampus and striatum that are associated with differential behavioral abnormalities in social, repetitive, locomotor, and anxiety-like domains.

https://ift.tt/2FgKUic

Late neuroprogenitors contribute to normal retinal vascular development in a Hif2a-dependent manner [RESEARCH ARTICLE]

Enrico Cristante, Sidath E. Liyanage, Robert D. Sampson, Aikaterini Kalargyrou, Giulia De Rossi, Matteo Rizzi, Justin Hoke, Joana Ribeiro, Ryea N. Maswood, Yanai Duran, Takaaki Matsuki, Nozie D. Aghaizu, Ulrich F. Luhmann, Alexander J. Smith, Robin R. Ali, and James W. B. Bainbridge

In the adult central nervous system, endothelial and neuronal cells engage in tight cross-talk as key components of the so-called neurovascular unit. Impairment of this important relationship adversely affects tissue homeostasis, as observed in neurodegenerative conditions including Alzheimer's and Parkinson's disease. In development, the influence of neuroprogenitor cells on angiogenesis is poorly understood. Here, we show in mouse that these cells interact intimately with the growing retinal vascular network, and we identify a novel regulatory mechanism of vasculature development mediated by hypoxia-inducible factor 2a (Hif2a). By Cre-lox gene excision, we show that Hif2a in retinal neuroprogenitor cells upregulates the expression of the pro-angiogenic mediators vascular endothelial growth factor and erythropoietin, whereas it locally downregulates the angiogenesis inhibitor endostatin. Importantly, absence of Hif2a in retinal neuroprogenitor cells causes a marked reduction of proliferating endothelial cells at the angiogenic front. This results in delayed retinal vascular development, fewer major retinal vessels and reduced density of the peripheral deep retinal vascular plexus. Our findings demonstrate that retinal neuroprogenitor cells are a crucial component of the developing neurovascular unit.

https://ift.tt/2HuoE6v

Suppression of epithelial folding at actomyosin-enriched compartment boundaries downstream of Wingless signalling in Drosophila [RESEARCH ARTICLE]

Jose M. Urbano, Huw W. Naylor, Elena Scarpa, Leila Muresan, and Benedicte Sanson

Epithelial folding shapes embryos and tissues during development. Here, we investigate the coupling between epithelial folding and actomyosin-enriched compartmental boundaries. The mechanistic relationship between the two is unclear, because actomyosin-enriched boundaries are not necessarily associated with folds. Also, some cases of epithelial folding occur independently of actomyosin contractility. We investigated the shallow folds called parasegment grooves that form at boundaries between anterior and posterior compartments in the early Drosophila embryo. We demonstrate that formation of these folds requires the presence of an actomyosin enrichment along the boundary cell-cell contacts. These enrichments, which require Wingless signalling, increase interfacial tension not only at the level of the adherens junctions but also along the lateral surfaces. We find that epithelial folding is normally under inhibitory control because different genetic manipulations, including depletion of the Myosin II phosphatase Flapwing, increase the depth of folds at boundaries. Fold depth correlates with the levels of Bazooka (Baz), the Par-3 homologue, along the boundary cell-cell contacts. Moreover, Wingless and Hedgehog signalling have opposite effects on fold depth at the boundary that correlate with changes in Baz planar polarity.

https://ift.tt/2I1wkhO

Successive duplication-divergence mechanisms at the RCO locus contributed to leaf shape diversity in the Brassicaceae [RESEARCH ARTICLE]

Susanna Streubel, Michael Andre Fritz, Melanie Teltow, Christian Kappel, and Adrien Sicard

Gene duplication is a major driver for the increase of biological complexity. The divergence of newly duplicated paralogs may allow novel functions to evolve, while maintaining the ancestral one. Alternatively, partitioning the ancestral function among paralogs may allow parts of that role to follow independent evolutionary trajectories. We studied the REDUCED COMPLEXITY (RCO) locus, which contains three paralogs that have evolved through two independent events of gene duplication, and which underlies repeated events of leaf shape evolution within the Brassicaceae. In particular, we took advantage of the presence of three potentially functional paralogs in Capsella to investigate the extent of functional divergence among them. We demonstrate that the RCO copies control growth in different areas of the leaf. Consequently, the copies that are retained active in the different Brassicaceae lineages contribute to define the leaf dissection pattern. Our results further illustrate how successive gene duplication events and subsequent functional divergence can increase trait evolvability by providing independent evolutionary trajectories to specialized functions that have an additive effect on a given trait.

https://ift.tt/2Hr72sg

The DEAD-box RNA helicase Ddx39ab is essential for myocyte and lens development in zebrafish [RESEARCH ARTICLE]

Linlin Zhang, Yuxi Yang, Beibei Li, Ian C. Scott, and Xin Lou

RNA helicases from the DEAD-box family are found in almost all organisms and have important roles in RNA metabolism, including RNA synthesis, processing and degradation. The function and mechanism of action of most of these helicases in animal development and human disease remain largely unexplored. In a zebrafish mutagenesis screen to identify genes essential for heart development we identified a mutant that disrupts the gene encoding the RNA helicase DEAD-box 39ab (ddx39ab). Homozygous ddx39ab mutant embryos exhibit profound cardiac and trunk muscle dystrophy, along with lens abnormalities, caused by abrupt terminal differentiation of cardiomyocyte, myoblast and lens fiber cells. Loss of ddx39ab hindered splicing of mRNAs encoding epigenetic regulatory factors, including members of the KMT2 gene family, leading to misregulation of structural gene expression in cardiomyocyte, myoblast and lens fiber cells. Taken together, these results show that Ddx39ab plays an essential role in establishment of the proper epigenetic status during differentiation of multiple cell lineages.

https://ift.tt/2I1weXu

Control of the proportion of inner cells by asymmetric divisions and the ensuing resilience of cloned rabbit embryos [RESEARCH REPORT]

Dimitri Fabreges, Nathalie Daniel, Veronique Duranthon, and Nadine Peyrieras

Mammalian embryo cloning by nuclear transfer has a low success rate. This is hypothesized to correlate with a high variability of early developmental steps that segregate outer cells, which are fated to extra-embryonic tissues, from inner cells, which give rise to the embryo proper. Exploring the cell lineage of wild-type embryos and clones, imaged in toto until hatching, highlights the respective contributions of cell proliferation, death and asymmetric divisions to phenotypic variability. Preferential cell death of inner cells in clones, probably pertaining to the epigenetic plasticity of the transferred nucleus, is identified as a major difference with effects on the proportion of inner cell. In wild type and clones, similar patterns of outer cell asymmetric divisions are shown to be essential to the robust proportion of inner cells observed in wild type. Asymmetric inner cell division, which is not described in mice, is identified as a regulator of the proportion of inner cells and likely gives rise to resilient clones.

https://ift.tt/2HrEjDC

Conserved and divergent functions of Pax6 underlie species-specific neurogenic patterns in the developing amniote brain [RESEARCH ARTICLE]

Wataru Yamashita, Masanori Takahashi, Takako Kikkawa, Hitoshi Gotoh, Noriko Osumi, Katsuhiko Ono, and Tadashi Nomura

The evolution of unique organ structures is associated with changes in conserved developmental programs. However, characterizing the functional conservation and variation of homologous transcription factors (TFs) that dictate species-specific cellular dynamics has remained elusive. Here, we dissect shared and divergent functions of Pax6 during amniote brain development. Comparative functional analyses revealed that the neurogenic function of Pax6 is highly conserved in the developing mouse and chick pallium, whereas stage-specific binary functions of Pax6 in neurogenesis are unique to mouse neuronal progenitors, consistent with Pax6-dependent temporal regulation of Notch signaling. Furthermore, we identified that Pax6-dependent enhancer activity of Dbx1 is extensively conserved between mammals and chick, although Dbx1 expression in the developing pallium is highly divergent in these species. Our results suggest that spatiotemporal changes in Pax6-dependent regulatory programs contributed to species-specific neurogenic patterns in mammalian and avian lineages, which underlie the morphological divergence of the amniote pallial architectures.

https://ift.tt/2HZGnnq

An interview with Christiana Ruhrberg [SPOTLIGHT]

Aidan Maartens

Christiana Ruhrberg is Professor of Neuronal and Vascular Biology at the UCL Institute of Ophthalmology in London. Her lab investigates the relationship between nerve and blood vessel development in the central nervous system. In 2018, she was awarded the British Society for Developmental Biology's Cheryll Tickle Medal, which recognises outstanding achievements of mid-career female scientists in the field. In advance of her medal lecture at the society's spring meeting, we met Christiana to find out what the award means to her, how she settled on neurovascular development after many changes in direction early in her career and her thoughts on what makes a good scientific mentor.

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The role of mitochondria in stem cell fate and aging [REVIEW]

Hongbo Zhang, Keir J. Menzies, and Johan Auwerx

The importance of mitochondria in energy metabolism, signal transduction and aging in post-mitotic tissues has been well established. Recently, the crucial role of mitochondrial-linked signaling in stem cell function has come to light and the importance of mitochondria in mediating stem cell activity is becoming increasingly recognized. Despite the fact that many stem cells exhibit low mitochondrial content and a reliance on mitochondrial-independent glycolytic metabolism for energy, accumulating evidence has implicated the importance of mitochondrial function in stem cell activation, fate decisions and defense against senescence. In this Review, we discuss the recent advances that link mitochondrial metabolism, homeostasis, stress responses, and dynamics to stem cell function, particularly in the context of disease and aging. This Review will also highlight some recent progress in mitochondrial therapeutics that may present attractive strategies for improving stem cell function as a basis for regenerative medicine and healthy aging.

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Coordinated directional outgrowth and pattern formation by integration of Wnt5a and Fgf signaling in planar cell polarity [RESEARCH ARTICLE]

Bo Gao, Rieko Ajima, Wei Yang, Chunyu Li, Hai Song, Matthew J. Anderson, Robert R. Liu, Mark B. Lewandoski, Terry P. Yamaguchi, and Yingzi Yang

Embryonic morphogenesis of a complex organism requires proper regulation of patterning and directional growth. Planar cell polarity (PCP) signaling is emerging as a crucial evolutionarily conserved mechanism whereby directional information is conveyed. PCP is thought to be established by global cues, and recent studies have revealed an instructive role of a Wnt signaling gradient in epithelial tissues of both invertebrates and vertebrates. However, it remains unclear whether Wnt/PCP signaling is regulated in a coordinated manner with embryonic patterning during morphogenesis. Here, in mouse developing limbs, we find that apical ectoderm ridge-derived Fgfs required for limb patterning regulate PCP along the proximal-distal axis in a Wnt5a-dependent manner. We demonstrate with genetic evidence that the Wnt5a gradient acts as a global cue that is instructive in establishing PCP in the limb mesenchyme, and that Wnt5a also plays a permissive role to allow Fgf signaling to orient PCP. Our results indicate that limb morphogenesis is regulated by coordination of directional growth and patterning through integration of Wnt5a and Fgf signaling.

https://ift.tt/2Hr1Zbb

p53: emerging roles in stem cells, development and beyond [PRIMER]

Abhinav K. Jain and Michelle Craig Barton

Most human cancers harbor mutations in the gene encoding p53. As a result, research on p53 in the past few decades has focused primarily on its role as a tumor suppressor. One consequence of this focus is that the functions of p53 in development have largely been ignored. However, recent advances, such as the genomic profiling of embryonic stem cells, have uncovered the significance and mechanisms of p53 functions in mammalian cell differentiation and development. As we review here, these recent findings reveal roles that complement the well-established roles for p53 in tumor suppression.

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Spatial and Temporal Control of T Cell Activation Using a Photoactivatable Agonist

This protocol describes an imaging-based method to activate T lymphocytes using photoactivatable peptide-MHC, enabling precise spatiotemporal control of T cell activation.

https://ift.tt/2KcPFgs

Well-aligned Vertically Oriented ZnO Nanorod Arrays and their Application in Inverted Small Molecule Solar Cells

This manuscript describes how to design and fabricate efficient inverted SMPV1:PC71BM solar cells with ZnO nanorods (NRs) grown on a high quality Al-doped ZnO (AZO) seed layer. The well-aligned vertically oriented ZnO NRs exhibit high crystalline properties. The power conversion efficiency of solar cells can reach 6.01%.

https://ift.tt/2FhfDLX

Effect of a single intra-articular injection of bupivacaine on synovial fluid prostaglandin E2 concentrations in normal canine stifles

To identify if synovial fluid prostaglandin E2 increases in response to a single intra-articular dose of bupivacaine in the normal canine stifle.

https://ift.tt/2Joquq6

A single-arm pilot study of guided self-help treatment based cognitive behavioral therapy for bulimia nervosa in Japanese clinical settings

Guided self-help treatments based on cognitive behavioral therapy (CBT-GSH) are regarded as a first-line effective treatment for bulimia nervosa (BN). With limited application for CBT-GSH in Japanese clinical ...

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Three-dimensional reconstruction of root shape in the moth orchid Phalaenopsis sp.: a biomimicry methodology for robotic applications

Within the field of biorobotics, an emerging branch is plant-inspired robotics. Some effort exists in particular towards the production of digging robots that mimic roots; for these, a deeper comprehension of ...

https://ift.tt/2JtjuIj

Challenges in the management of cardiovascular emergencies in Sub-Saharan Africa: a case report of acute heart failure complicating infective endocarditis in a semi-urban setting in Cameroon

Infective endocarditis is a deadly disease if not promptly treated with antibiotics either in association with cardiac surgery or not. Cardiac complications are the most common complications seen in infective ...

https://ift.tt/2HT3Qct

Ectopic thymoma in the paratracheal region of the middle mediastinum: a rare case report and literature review

Thymomas generally arise from the thymus in the anterior mediastinum. Ectopic thymomas arising in the middle mediastinum are rare. We present a case of a thymoma arising from the ectopic thymic tissue in the r...

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VDR signaling inhibits cancer-associated-fibroblasts release of exosomal miR-10a-5p and limits their supportive effects on pancreatic cancer cells

We read with great interest the recent publication by Ferrer-Mayorga et al,1 concerning Vitamin D receptor (VDR) signalling's impacts on cancer-associated fibroblasts (CAFs) in colorectal cancer (CRC). In line with one previous publication regarding VDR in pancreatic cancer (PC),2 activation of VDR signalling in stromal fibroblasts predicts a favourable clinical outcome in CRC. Both reports set the concept in principle that VDR agonists can be explored as a therapy against tumor-associated stroma in PC and CRC. However, detailed mechanisms involved in VDR's regulation of tumor-stroma crosstalk remained to be elucidated.

Recent publications identified exosomal miRNAs as critical mediators for cellular communication. In this study, we aimed to investigate whether exosomal miRNAs were implicated in VDR's regulation against the protumoural activity of CAFs. Three immortalised CAF cell lines were generated from PC patients following the protocol reported previously.3 Exosomes released by CAFs were labelled with fluorescent...

https://ift.tt/2JpP0qF

Cancer Control in American Indian and Alaska Native Populations: A Conversation with Dr. Shobha Srinivasan

American Indian and Alaska Native populations are disproportionately affected by certain cancers. In this interview, Dr. Shobha Srinivasan discusses some of these disparities and programs funded by NCI that are helping to address them.

https://ift.tt/2qYiWDw

Adaptation to Noise in Human Speech Recognition Unrelated to the Medial Olivocochlear Reflex

Sensory systems constantly adapt their responses to the current environment. In hearing, adaptation may facilitate communication in noisy settings, a benefit frequently (but controversially) attributed to the medial olivocochlear reflex (MOCR) enhancing the neural representation of speech. Here, we show that human listeners (N = 14; five male) recognize more words presented monaurally in ipsilateral, contralateral, and bilateral noise when they are given some time to adapt to the noise. This finding challenges models and theories that claim that speech intelligibility in noise is invariant over time. In addition, we show that this adaptation to the noise occurs also for words processed to maintain the slow-amplitude modulations in speech (the envelope) disregarding the faster fluctuations (the temporal fine structure). This demonstrates that noise adaptation reflects an enhancement of amplitude modulation speech cues and is unaffected by temporal fine structure cues. Last, we show that cochlear implant users (N = 7; four male) show normal monaural adaptation to ipsilateral noise. Because the electrical stimulation delivered by cochlear implants is independent from the MOCR, this demonstrates that noise adaptation does not require the MOCR. We argue that noise adaptation probably reflects adaptation of the dynamic range of auditory neurons to the noise level statistics.

SIGNIFICANCE STATEMENT People find it easier to understand speech in noisy environments when they are given some time to adapt to the noise. This benefit is frequently but controversially attributed to the medial olivocochlear efferent reflex enhancing the representation of speech cues in the auditory nerve. Here, we show that the adaptation to noise reflects an enhancement of the slow fluctuations in amplitude over time that are present in speech. In addition, we show that adaptation to noise for cochlear implant users is not statistically different from that for listeners with normal hearing. Because the electrical stimulation delivered by cochlear implants is independent from the medial olivocochlear efferent reflex, this demonstrates that adaptation to noise does not require this reflex.

https://ift.tt/2HrmggK

Dual Coding of Frequency Modulation in the Ventral Cochlear Nucleus

Frequency modulation (FM) is a common acoustic feature of natural sounds and is known to play a role in robust sound source recognition. Auditory neurons show precise stimulus-synchronized discharge patterns that may be used for the representation of low-rate FM. However, it remains unclear whether this representation is based on synchronization to slow temporal envelope (ENV) cues resulting from cochlear filtering or phase locking to faster temporal fine structure (TFS) cues. To investigate the plausibility of those encoding schemes, single units of the ventral cochlear nucleus of guinea pigs of either sex were recorded in response to sine FM tones centered at the unit's best frequency (BF). The results show that, in contrast to high-BF units, for modulation depths within the receptive field, low-BF units (<4 kHz) demonstrate good phase locking to TFS. For modulation depths extending beyond the receptive field, the discharge patterns follow the ENV and fluctuate at the modulation rate. The receptive field proved to be a good predictor of the ENV responses for most primary-like and chopper units. The current in vivo data also reveal a high level of diversity in responses across unit types. TFS cues are mainly conveyed by low-frequency and primary-like units and ENV cues by chopper and onset units. The diversity of responses exhibited by cochlear nucleus neurons provides a neural basis for a dual-coding scheme of FM in the brainstem based on both ENV and TFS cues.

SIGNIFICANCE STATEMENT Natural sounds, including speech, convey informative temporal modulations in frequency. Understanding how the auditory system represents those frequency modulations (FM) has important implications as robust sound source recognition depends crucially on the reception of low-rate FM cues. Here, we recorded 115 single-unit responses from the ventral cochlear nucleus in response to FM and provide the first physiological evidence of a dual-coding mechanism of FM via synchronization to temporal envelope cues and phase locking to temporal fine structure cues. We also demonstrate a diversity of neural responses with different coding specializations. These results support the dual-coding scheme proposed by psychophysicists to account for FM sensitivity in humans and provide new insights on how this might be implemented in the early stages of the auditory pathway.

https://ift.tt/2HYVJZe

Low-Dimensional and Monotonic Preparatory Activity in Mouse Anterior Lateral Motor Cortex

Neurons in multiple brain regions fire trains of action potentials anticipating specific movements, but this "preparatory activity" has not been systematically compared across behavioral tasks. We compared preparatory activity in auditory and tactile delayed-response tasks in male mice. Skilled, directional licking was the motor output. The anterior lateral motor cortex (ALM) is necessary for motor planning in both tasks. Multiple features of ALM preparatory activity during the delay epoch were similar across tasks. First, most neurons showed direction-selective activity and spatially intermingled neurons were selective for either movement direction. Second, many cells showed mixed coding of sensory stimulus and licking direction, with a bias toward licking direction. Third, delay activity was monotonic and low-dimensional. Fourth, pairs of neurons with similar direction selectivity showed high spike-count correlations. Our study forms the foundation to analyze the neural circuit mechanisms underlying preparatory activity in a genetically tractable model organism.

SIGNIFICANCE STATEMENT Short-term memories link events separated in time. Neurons in the frontal cortex fire trains of action potentials anticipating specific movements, often seconds before the movement. This "preparatory activity" has been observed in multiple brain regions, but has rarely been compared systematically across behavioral tasks in the same brain region. To identify common features of preparatory activity, we developed and compared preparatory activity in auditory and tactile delayed-response tasks in mice. The same cortical area is necessary for both tasks. Multiple features of preparatory activity, measured with high-density silicon probes, were similar across tasks. We find that preparatory activity is low-dimensional and monotonic. Our study forms a foundation for analyzing the circuit mechanisms underlying preparatory activity in a genetically tractable model organism.

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Restoration of Kv7 Channel-Mediated Inhibition Reduces Cued-Reinstatement of Cocaine Seeking

Cocaine addicts display increased sensitivity to drug-associated cues, due in part to changes in the prelimbic prefrontal cortex (PL-PFC). The cellular mechanisms underlying cue-induced reinstatement of cocaine seeking remain unknown. Reinforcement learning for addictive drugs may produce persistent maladaptations in intrinsic excitability within sparse subsets of PFC pyramidal neurons. Using a model of relapse in male rats, we sampled >600 neurons to examine spike frequency adaptation (SFA) and afterhyperpolarizations (AHPs), two systems that attenuate low-frequency inputs to regulate neuronal synchronization. We observed that training to self-administer cocaine or nondrug (sucrose) reinforcers decreased SFA and AHPs in a subpopulation of PL-PFC neurons. Only with cocaine did the resulting hyperexcitability persist through extinction training and increase during reinstatement. In neurons with intact SFA, dopamine enhanced excitability by inhibiting Kv7 potassium channels that mediate SFA. However, dopamine effects were occluded in neurons from cocaine-experienced rats, where SFA and AHPs were reduced. Pharmacological stabilization of Kv7 channels with retigabine restored SFA and Kv7 channel function in neuroadapted cells. When microinjected bilaterally into the PL-PFC 10 min before reinstatement testing, retigabine reduced cue-induced reinstatement of cocaine seeking. Last, using cFos-GFP transgenic rats, we found that the loss of SFA correlated with the expression of cFos-GFP following both extinction and re-exposure to drug-associated cues. Together, these data suggest that cocaine self-administration desensitizes inhibitory Kv7 channels in a subpopulation of PL-PFC neurons. This subpopulation of neurons may represent a persistent neural ensemble responsible for driving drug seeking in response to cues.

SIGNIFICANCE STATEMENT Long after the cessation of drug use, cues associated with cocaine still elicit drug-seeking behavior, in part by activation of the prelimbic prefrontal cortex (PL-PFC). The underlying cellular mechanisms governing these activated neurons remain unclear. Using a rat model of relapse to cocaine seeking, we identified a population of PL-PFC neurons that become hyperexcitable following chronic cocaine self-administration. These neurons show persistent loss of spike frequency adaptation, reduced afterhyperpolarizations, decreased sensitivity to dopamine, and reduced Kv7 channel-mediated inhibition. Stabilization of Kv7 channel function with retigabine normalized neuronal excitability, restored Kv7 channel currents, and reduced drug-seeking behavior when administered into the PL-PFC before reinstatement. These data highlight a persistent adaptation in a subset of PL-PFC neurons that may contribute to relapse vulnerability.

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