Medicine by Alexandros G.Sfakianakis: 08/09/18

Πέμπτη 9 Αυγούστου 2018

Physiological and pathological high frequency oscillations in focal epilepsy

Annals of Clinical and Translational Neurology, EarlyView.

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Three‐dimensional laparoscopy‐assisted bowel resection for cavernous hemangioma of the rectum: Report of two cases

Asian Journal of Endoscopic Surgery, EarlyView.

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Accusers Lie and Other Myths: Rape Myth Acceptance Predicts Judgments Made About Accusers and Accused Perpetrators in a Rape Case

Abstract

Previous research results have yielded a consistent link between rape myth acceptance and sexual assault victim blaming: Individuals reporting higher levels of rape myth acceptance also report higher levels of victim blaming. In four studies we explored whether the presentation of rape-myth confirming information or rape-myth debunking information might moderate these tendencies. In these studies, U.S. undergraduates (97 in Study 1, 84 in Study 2, 98 in Study 3, and 116 in Study 4) read scenarios of a heterosexual sexual assault case and were randomly assigned to a control condition, a rape myth confirmation condition, or a rape myth debunking condition; they also reported the extent to which they endorsed or accepted rape myths. Rape myth acceptance robustly correlated with judgments made about accusers and accused rapists regardless whether the accuser/accused pairing was female/male (Studies 1 and 2) or male/female (Studies 3 and 4). For example, those who most strongly endorsed rape myths were also likely to disbelieve accusers. There were few instances indicating that the presentation of rape myth confirming information or rape myth debunking information moderated these effects. This lack of moderation occurred regardless of whether the information came from trial lawyers or from expert witnesses in the case. The relative impotence of the information presentations could be due to several factors (e.g., entrenched nature of rape myth acceptance, psychological reactance, timing and strength of manipulation), and we suggest ideas for how to overcome this relative impotence in future research.

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Providing postpartum care with limited resources: Experiences of nurse-midwives and obstetricians in urban Tanzania

Publication date: Available online 9 August 2018

Source: Women and Birth

Author(s): Danielle Macdonald, Megan Aston, Gail Tomblin Murphy, Keisha Jefferies, Lilian T. Mselle, Sheri Price, Shawna O'Hearn, Maureen White, Columba Mbekenga, Thecla W. Kohi

Abstract

Background

Tanzania has high maternal and neonatal mortality rates. Comprehensive guidelines for postpartum care have been developed by the government as a means to improve health outcomes during the perinatal period. Despite the creation of these guidelines and the government's commitment to universal perinatal care for women and neonates, there is concern that the delivery of postpartum services may not be meeting the needs of mothers and neonates.

Aim

The purpose of this feminist poststructuralist study was to explore nurse-midwives' and obstetricians' experiences of providing postpartum care in Tanzania.

Methods

This qualitative study used feminist poststructuralism to explore the personal, social, and institutional discourses of postpartum care. We individually interviewed ten nurse-midwives and three obstetricians in Dar es Salaam, Tanzania. Feminist poststructuralist discourse analysis was used to analyze the transcribed interviews after their translation from Kiswahili to English.

Findings

Four main themes were identified. In this paper, we present the main theme of availability of resources, and its four corresponding subthemes; (1) space, (2) equipment, (3) staffing, and (4) government responsibility.

Discussion

The findings from our study illustrate the need for health workforce planning to be addressed in a comprehensive manner that accounts for context, required resources and systemic challenges. These findings are consistent with findings from other studies.

Conclusion

Understanding the resource challenges that nurse-midwives and obstetricians are facing in one low-and-middle-income-country will assist researchers, decision makers, and politicians as they address issues of mortality, morbidity, and disrespectful maternity care.

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Comment on: Sensitivity Analysis for Not-at-Random Missing Data in Trial-Based Cost-Effectiveness Analysis: A Tutorial

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Application of prophylactic cranial irradiation in limited-stage small-cell lung cancer: which patients could benefit?

Future Oncology, Ahead of Print.

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Clinical outcomes with long-term sorafenib treatment of patients with hepatocellular carcinoma: a multicenter real-life study

Future Oncology, Ahead of Print.

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Feifukang ameliorates pulmonary fibrosis by inhibiting JAK-STAT signaling pathway

Feifukang (FFK) is a traditional Chinese medicine composed of herbs that protect lung function. However, difficulty arises regarding the clinical application of FFK due to the complex mechanism of Chinese medi...

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The management strategies of cancer-associated anorexia: a critical appraisal of systematic reviews

Cancer-related anorexia remains one of the most prevalent and troublesome clinical problems experienced by patients with cancer during and after therapy. To ensure high-quality care, systematic reviews (SRs) a...

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Sotetsuflavone inhibits proliferation and induces apoptosis of A549 cells through ROS-mediated mitochondrial-dependent pathway

Sotetsuflavone is isolated from Cycas revoluta Thunb., which has biological activity against tumors. However, the anti-proliferative effects of sotetsuflavone on A549 cells and its mechanism are not fully elucida...

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Repotrectinib (TPX-0005) is a next generation ROS1/TRK/ALK inhibitor that potently inhibits ROS1/TRK/ALK solvent front mutations [Research Briefs]

The use of tyrosine kinase inhibitors (TKIs) with activity against ALK, ROS1, or TRKA-C can result in significant clinical benefit in patients with diverse tumors harboring ALK, ROS1 or NTRK1-3 rearrangements; however, resistance invariably develops. The emergence of on-target kinase domain mutations represents a major mechanism of acquired resistance. Solvent front substitutions such as ALK G1202R, ROS1 G2032R or D2033N, TRKA G595R, and TRKC G623R are among the most recalcitrant of these mechanisms. Repotrectinib (TPX-0005) is a rationally-designed, low molecular weight, macrocyclic TKI that is selective and highly potent against ROS1, TRKA-C, and ALK. Importantly, repotrectinib exhibits activity against a variety of solvent front substitutions in vitro and in vivo. As clinical proof of concept, in an on-going first-in-human phase 1/2 trial, repotrectinib achieved confirmed responses in patients with ROS1 or NTRK3 fusion-positive cancers who had relapsed on earlier generation TKIs due to ROS1 or TRKC solvent front substitution-mediated resistance.

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The BTK Inhibitor ARQ 531 Targets Ibrutinib Resistant CLL and Richter's Transformation [Research Articles]

Targeted inhibition of Bruton's tyrosine kinase (BTK) with the irreversible inhibitor ibrutinib has improved outcomes for patients with hematologic malignancies, including chronic lymphocytic leukemia (CLL). Here we describe preclinical investigations of ARQ 531, a potent, reversible inhibitor of BTK with additional activity against Src family kinases and kinases related to ERK signaling. We hypothesized that targeting additional kinases would improve global inhibition of signaling pathways, producing more robust responses. In vitro treatment of patient CLL cells with ARQ 531 decreases BTK-mediated functions including B cell receptor (BCR) signaling, viability, migration, CD40 and CD86 expression, and NF-B gene transcription. In vivo, ARQ 531 was found to increase survival over ibrutinib in a murine Eμ-TCL1 engraftment model of CLL and a murine Eμ-MYC/TCL1 engraftment model resembling Richter's transformation. Additionally, ARQ 531 inhibits CLL cell survival and suppresses BCR-mediated activation of C481S BTK and PLC2 mutations which facilitate clinical resistance to ibrutinib.

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Ivosidenib Gets Go-Ahead for AML [News in Brief]

First IDH1 inhibitor could dramatically improve treatment for some patients with acute myeloid leukemia.

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CRISPR Causes Unexpected Genomic Damage [News in Brief]

Genome-editing method requires further precautions, researchers say.

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Intratumoral G100, a TLR4 agonist, induces anti-tumor immune responses and tumor regression in patients with Merkel cell carcinoma

Purpose: G100 is a toll-like receptor 4 (TLR4) agonist that triggers innate and adaptive anti-tumor immune responses in preclinical models. This pilot study assessed the safety, efficacy, and immunologic activity of intratumoral (IT) administration of G100 in patients with Merkel cell carcinoma (MCC). Experimental Design: Patients with loco-regional MCC (n=3; Cohort A) received neoadjuvant IT G100 (2 weekly doses at 5 μg/dose) followed by surgery and radiotherapy; patients with metastatic MCC (n=7; Cohort B) received 3 doses in a 6-week cycle and could receive additional cycles with/without radiotherapy. Results: IT G100 was safe and feasible in both neoadjuvant and metastatic settings. Treatment-related adverse events were mostly grade 1 or 2 injection site reactions. IT G100 led to increased inflammation in the injected tumors with infiltration of CD8⁺and CD4⁺T cells and activation of immune-related genes. These pro-inflammatory changes were associated with local tumor regression and appeared to promote systemic immunity. All 3 Cohort A patients successfully completed therapy; 2 patients remain recurrence-free at 44+ and 41+ months, including one with a pathologic complete response after G100 alone. In Cohort B, 2 patients achieved sustained partial responses, both lasting 33+ months after 2 cycles of therapy. Conclusions: In this first-in-human study, IT G100 induced anti-tumor immune responses, demonstrated acceptable safety, and showed encouraging clinical activity.

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Early reduction in ctDNA predicts survival in lung and bladder cancer patients treated with durvalumab

Purpose: Immunotherapy has transformed the treatment of many solid tumors, with some patients deriving long-term benefit, but how to identify such patients remains unclear. Somatic mutations detected in circulating tumor DNA (ctDNA) from plasma can be an indicator of disease progression, response to therapy and clonality of primary and metastatic lesions. Hence, ctDNA analysis can provide a valuable noninvasive and tumor-specific marker for longitudinal monitoring of tumor burden. We explored the use of ctDNA to predict survival on durvalumab, an anti-PD-L1 therapy. Experimental design: Variant allele frequencies (VAF) of somatic mutations in 73 genes were assessed in ctDNA using targeted sequencing in a discovery cohort consisting of 28 non-small cell lung cancer (NSCLC) patients and two validation NSCLC and urothelial cancer (UC) cohorts of 72 and 29 patients respectively, to correlate ctDNA changes with clinical outcomes. Results: Somatic variants were detected in 96% of patients. Changes in VAF preceded radiographic responses, and patients with reduction in VAF at 6 weeks had significantly greater reduction in tumor volume, with longer progression-free and overall survival. Conclusions: ctDNA VAF changes are strongly correlated with duration of treatment, antitumor activity and clinical outcomes in NSCLC and UC. Early on-treatment reduction in ctDNA VAF may be a useful predictor of long-term benefit from immunotherapy. Prospective studies should validate these findings and the value of utilizing early changes in ctDNA for therapeutic decision-making by identifying non-responders to checkpoint inhibitor monotherapies and guiding combination therapies.

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Single Cell Analyses of Prostate Cancer Liquid Biopsies Acquired by Apheresis

Purpose: Circulating tumor cells (CTCs) have clinical relevance, but their study has been limited by their low frequency. Experimental Design: We evaluated liquid biopsies by apheresis to increase CTC yield from patients suffering from metastatic prostate cancer, allow precise gene copy number calls, and study disease heterogeneity. Results: Apheresis was well-tolerated and allowed the separation of large numbers of CTCs; the average CTC yield from 7.5mls of peripheral blood was 167 CTCs, whereas the average CTC yield per apheresis (mean volume: 59.5mls) was 12546 CTCs. Purified single CTCs could be isolated from apheresis product by FACS sorting; copy number aberration (CNA) profiles of 185 single CTCs from 14 patients revealed the genomic landscape of lethal prostate cancer and identified complex intra-patient, inter-cell, genomic heterogeneity missed on bulk biopsy analyses. Conclusion/Discussion: Apheresis facilitated the capture of large numbers of CTCs non-invasively with minimal morbidity and allowed the deconvolution of intra-patient heterogeneity and clonal evolution.

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Role of the RANK/RANKL Pathway in Multiple Myeloma

Receptor activator of nuclear factor-kappa B (RANK) and its ligand, RANKL, are expressed in a variety of tissues throughout the body; their primary role is in the regulation of bone remodeling and development of the immune system. Consistent with these functions, evidence exists for a role of RANK/RANKL in all stages of tumorigenesis, from cell proliferation and carcinogenesis, epithelial-mesenchymal transition, neoangiogenesis and intravasation, metastasis, and bone resorption and tumor growth in bone. Results from current studies also point to a role of RANK/RANKL signaling in patients with multiple myeloma, who have increased serum levels of soluble RANKL and an imbalance in RANKL and osteoprotegerin. Current therapies for patients with multiple myeloma demonstrate that RANKL may be released by tumor cells or osteoprogenitor cells. This article will review currently available evidence supporting a role for RANK/RANKL signaling in tumorigenesis, with a focus on patients with multiple myeloma.

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Rates of ERBB2 Alterations Across Melanoma Subtypes and a Complete Response to Trastuzumab Emtansine in an ERBB2-amplified Acral Melanoma

Purpose: Patients with BRAF V600-wild type melanoma whose tumors progress on checkpoint inhibition currently have limited therapeutic options, and additional rational treatment targets are needed. ERBB2 alterations may be amenable to targeted inhibition, but the rate of ERBB2 alterations across melanoma subtypes is not well described. Experimental Design: All patients with non-uveal melanoma (cutaneous, acral, mucosal, and unknown primary) whose tumors underwent multigene sequencing with MSK-IMPACT at Memorial Sloan Kettering Cancer Center from 2014-2018 were reviewed for known or likely oncogenic somatic alterations in ERBB2 and the other known canonical driver genes BRAF, NRAS, KIT, NF1, GNAQ, and GNA11. Results: A patient with acral melanoma resistant to checkpoint inhibition was found to have an ERBB2 amplification and achieved a durable complete response to trastuzumab emtansine. Tumor sequencing results from 732 melanoma cases were analyzed for ERBB2 and canonical driver gene alterations. ERBB2 amplifications were detected in acral (3%) and mucosal (3%) melanomas. ERBB2 mutations were found in cutaneous (1%), acral (2%), and mucosal (2%) subtypes and frequently co-occurred with NF1 alterations. Among the 140 patients whose tumors lacked canonical driver alterations, ERBB2 amplifications were detected in acral (7%) and mucosal (6%) melanoma. Conclusions: ERBB2 amplification is present in a minority of acral lentiginous and mucosal melanomas. Activating mutations in ERBB2 were identified in non-uveal melanoma subtypes and are frequently co-mutated with canonical drivers. HER2 could represent a therapeutically relevant target across melanoma subtypes.

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Identification of Tissue Specific DNA Methylation Signatures for Thyroid Nodule Diagnostics

Purpose: Thyroid cancer is frequently difficult to diagnose due to an overlap of cytological features between malignant and benign nodules. This overlap leads to unnecessary removal of the thyroid in patients without cancer. While providing some improvement over cytopathologic diagnostics, molecular methods frequently fail to provide a correct diagnosis for thyroid nodules. These approaches are based on the difference between cancer and adjacent thyroid tissue and assume that adjacent tissues are the same as benign nodules. However, in contrast to adjacent tissues, benign thyroid nodules can contain genetic alterations that can be found in cancer. Experimental Design: For the development of a new molecular diagnostic test for thyroid cancer, we evaluated DNA methylation in 109 thyroid tissues by using genome wide single base resolution DNA methylation analysis. The test was validated in a retrospective cohort containing 65 thyroid nodules. Results: By conducting Reduced Representation Bisulfite Sequencing in 109 thyroid specimens, we found significant differences between adjacent tissue, benign nodules, and cancer. These tissue specific signatures are strongly linked to active enhancers and cancer associated genes. Based on these signatures, we developed a new epigenetic approach for thyroid diagnostics. According to the validation cohort, our test has an estimated specificity of 97% (95% CI, 81 to 100), sensitivity of 100% (95% CI, 87 to 100), PPV of 97% (95% CI, 83-100), and NPV of 100% (95% CI, 86 to 100). Conclusions: These data show that epigenetic testing can provide outstanding diagnostic accuracy for thyroid nodules.

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Phase 2 Trial of Alisertib in Combination with Irinotecan and Temozolomide for Patients with Relapsed or Refractory Neuroblastoma

Purpose: In phase 1 testing, alisertib tablets with irinotecan and temozolomide showed significant antitumor activity in patients with neuroblastoma. The current study sought to: confirm activity of this regimen; evaluate an alisertib oral solution (OS); and evaluate biomarkers of clinical outcomes. Methods: We conducted a two-stage phase 2 trial of alisertib tablets (60 mg/m2/dose x 7 days), irinotecan (50 mg/m2/dose IV x 5 days), and temozolomide (100 mg/m2/dose orally x 5 days) in patients with relapsed or refractory neuroblastoma. The primary endpoint was best objective response. A separate cohort was treated with alisertib at 45 mg/m2 using OS instead of tablets. Exploratory analyses sought to identify predictors of toxicity, response, and progression-free survival (PFS) using pooled data from phase 1, phase 2, and OS cohorts. Results: Twenty and 12 eligible patients were treated in the phase 2 and OS cohorts, respectively. Hematologic toxicities were the most common adverse events. In phase 2, 4 partial responses were observed in 19 evaluable patients (21%). The estimated PFS at 1 year was 34%. In the OS cohort, 3 patients (25%) had first cycle dose-limiting toxicity (DLT). Alisertib OS at 45 mg/m2 had significantly higher median Cmax and exposure compared to tablets at 60 mg/m2. Higher alisertib trough concentration was associated with first cycle DLT, while MYCN amplification was associated with inferior PFS. Conclusion:This combination shows antitumor activity, particularly in patients with MYCN non-amplified tumors. Data on an alisertib oral solution expand the population able to be treated with this agent.

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Targeting the CDK4/6-Rb pathway enhances response to PI3K inhibition in PIK3CA mutant lung squamous cell carcinoma

Purpose: Lung squamous cell carcinoma (LUSC) is a major subtype of non-small cell lung cancer characterized by multiple genetic alterations, particularly PI3K pathway alterations which have been identified in over 50% of LUSC cases. Despite being an attractive target, single agent PI3K inhibitors have demonstrated modest response in LUSC. Thus, novel combination therapies targeting LUSC are needed. Experimental Design: PI3K inhibitors alone and in combination with CDK4/6 inhibitors were evaluated in previously established LUSC patient-derived xenografts (PDX) using an in vivo screening method. Screening results were validated with in vivo expansion to n=5-8 mice per arm. Pharmacodynamics studies were performed to confirm targeted inhibition of compounds. Results: Consistent with results from The Cancer Genome Atlas (TCGA) analysis of LUSC, genomic profiling of our large cohort of LUSC PDX models identified PI3K pathway alterations in over 50% of the models. In vivo screening using PI3K inhibitors in 12 of these models identified PIK3CA mutation as a predictive biomarker of response (<20% tumor growth compared to baseline/vehicle). Combined inhibition of PI3K and CDK4/6 in models with PIK3CA mutation resulted in greater anti-tumor effects compared to either monotherapy alone. Additionally, the combination of the two drugs achieved targeted inhibition of the PI3K and cell cycle pathways. Conclusions: PIK3CA mutations predict response to PI3K inhibitors in LUSC. Combined PI3K and CDK4/6 inhibition enhances response to either single agents alone. Our findings provide a rationale for clinical testing of combined PI3K and CDK4/6 inhibitors in PIK3CA mutant LUSC.

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Ultrahigh dose-rate radiotherapy: Next steps for FLASH-RT

A new way of delivering radiotherapy at very high dose-rates is described and compared to conventional radiotherapy. The ultrahigh dose-rate therapy reduces damage to normal pig skin and exerts potent activity against spontaneous nasal tumours in cat patients. The implications for clinical development of this approach are discussed.

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AHA: A Diverse Diet May Not Promote a Healthy Weight

THURSDAY, Aug. 9, 2018 -- The long-standing recommendation to eat a variety of foods may not be a sound way to promote healthy eating patterns and a healthy body weight, according to an American Heart Association science advisory published online...

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Feeling Young May Be Reflected in Brain Structure

TUESDAY, August 7, 2018 -- People who feel younger than their age show fewer signs of brain aging than those who feel their age or older than their age, according to a small study published recently in Frontiers in Aging Neuroscience. Seyul Kwak,...

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Parental Belief in Religion Lowers Child Suicide Risk

THURSDAY, Aug. 9, 2018 -- Parental belief in the importance of religion is associated with a decrease in risk in suicidal behavior in their offspring, according to a study published online Aug. 8 in JAMA Psychiatry. Connie Svob, Ph.D., from Columbia...

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AMA Adopts Policy to Advance Gender Equity in Medicine

THURSDAY, Aug. 9, 2018 -- The American Medical Association (AMA) House of Delegates has adopted a new policy to study, act for, and advocate to advance gender equity in medicine, according to a report published in the association's AMA Wire. As part...

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Vaccinations Begin in Congo Ebola Outbreak

THURSDAY, Aug. 9, 2018 -- Vaccinations against Ebola began yesterday in an effort to stem the latest outbreak in Congo. Three thousand doses of the experimental vaccine are being sent to North Kivu province. The first to be vaccinated will include...

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An Inflammatory Bowel Disease Mimic in a Patient With Human Immunodeficiency Virus

A 45-year-old man with human immunodeficiency virus infection and undetectable viral load on antiretroviral therapy, who engaged in sex with men, was evaluated for 1 month of constipation, abdominal pain, and intermittent rectal bleeding. He reported a transient rash, which resolved at presentation. A colonoscopy (Figure A) showed aphthous ulcers, friability, and exudates in the rectosigmoid colon and cecum with normal intervening colon and terminal ileum. A colonic biopsy (Figure B) showed long, undulating bacteria attached vertically to the brush border, and stained black with Warthin–Starry stain, consistent with human intestinal spirochetosis.

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Should we set-up routine screening for primary sclerosing cholangitis in all IBD patients?

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Prognostic factors in esophageal cancer treated with curative intent

The overall prognosis of patients with esophageal cancer has improved in recent decades due to surgical and medical progress, but overall survival remains poor. Better patient selection and tailored treatment are needed. Different prognostic factors linked with the patient, tumoral characteristics and treatment with curative intent have been identified and are the purpose of this review. Tumor detection at an earlier stage, the advent of new molecules and therapeutic combinations, and the centralization of management in high-volume centers should help to improve the prognosis of esophageal cancer.

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Unmet needs of Italian physicians managing patients with Inflammatory Bowel Disease

Little is known about the unmet needs of physicians caring for patients with inflammatory bowel disease (IBD).

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Anti-MAG neuropathy: role of IgM antibodies, the paranodal junction and juxtaparanodal potassium channels

Although the neuropathy associated with IgM antibodies against myelin-associated glycoprotein (MAG) has characteristic clinical, immunological and pathological features, there remains a gap in understanding the functional alterations underlying nerve dysfunction. Clinically, anti-MAG neuropathy is typically associated with a distal acquired demyelinating symmetric (DADS) phenotype characterised by a progressive predominantly sensory, distal neuropathy with distally accentuated conduction slowing seen on neurophysiology (Steck et al., 2006).

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A multi-center nested case-control study on hospitalization costs and length of stay due to healthcare-associated infection

In 2018, the Chinese government demanded nationwide implementation of medical insurance payment methods based on Single-Disease Payment (SDP), but during the operation process the medical insurance system did ...

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Enumerating the economic cost of antimicrobial resistance per antibiotic consumed to inform the evaluation of interventions affecting their use

Antimicrobial resistance (AMR) poses a colossal threat to global health and incurs high economic costs to society. Economic evaluations of antimicrobials and interventions such as diagnostics and vaccines that...

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Impact of matrix-assisted laser desorption/ionization time of flight mass spectrometric evaluation on the clinical outcomes of patients with bacteremia and fungemia in clinical settings lacking an antimicrobial stewardship program: a pre-post quasi experimental study

Several studies have evaluated the impact of matrix-assisted laser desorption/ionization time-of-flight (MALDI-TOF) mass spectrometry (MS) combined with antimicrobial stewardship in patients with positive bloo...

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Reply to “Harmful and beneficial effects of anticoagulants in patients with cirrhosis and portal vein thrombosis”

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Erroneous use of endoscopic biopsy data in Crohn’s disease

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A Rare Case of Asymptomatic Primary Gastric Localized Amyloidosis

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Anti-HBc Quantitation as a New Biomarker of Hepatitis B Virus Infection: Surrogate Markers Predicting Surrogate Endpoints

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Herpes esophagitis mimicking Candidiasis

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Patient, Procedure, and Endoscopist Risk Factors for Perforation, Bleeding, and Splenic Injury After Colonoscopies

We investigated perforations, bleeding, and splenic injuries after screening or diagnostic colonoscopies to identify patient-, procedure-, endoscopist-, and facility-associated risk factors.

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The Microbiome in Cirrhosis and its Complications

The microbiome in cirrhosis is affected by multiple processes occurring at the level of the gut and systemically. This dysbiosis, or unfavorable microbiota profile, is present at several body sites and is associated with higher systemic inflammation, bacterial infections and poor outcomes. This increased morbidity in cirrhosis stems from an immune paralysis state that is partly related to the constant stimulation of the immune system by this dysbiosis. Dysbiosis as a dynamic event worsens with decompensation such as with hepatic encephalopathy, infections or acute-on-chronic liver failure (ACLF).

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Neuroendocrine Tumor Presenting as a Large Gastric Ulcer

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When to Resume Direct Oral Anticoagulants Following Gastrointestinal Bleeding

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Sex-Based Differences in the Association between Non-alcoholic Fatty Liver Disease and Mortality

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Porphyria Cutanea Tarda Improvement with Elbasvir/Grazoprevir in End Stage Renal Disease

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Functional gastrointestinal symptoms in patients with inflammatory bowel disease: A clinical challenge

The purpose of this clinical practice update review is to describe key principles in the diagnosis and management of functional gastrointestinal (GI) symptoms in patients with inflammatory bowel disease (IBD).

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Cardiovascular Preventive Care and Coordination Of Care In Prostate Cancer Survivors: A Multi-Institutional Prospective Study

Prostate cancer survivors who receive androgen deprivation therapy (ADT) are at increased risk of cardiovascular disease. We prospectively enrolled 103 men receiving ADT to assess cardiovascular risk factors and survivorship care. Cardiovascular disease and risk factors were prevalent at baseline and 1 year, and less than two thirds received guideline concordant monitoring. In addition, patient's perception of coordination of care between primary care and specialists were low.

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Patterns of Failure following Postoperative Radiation Therapy Based on “Tumor Bed with Margin” for Stage II-IV Type C Thymic Epithelial Tumor

This retrospective study to report failure patterns and suitability of radiation target volume of "tumor bed only with margin" in Masaoka stage II-IV type C thymic epithelial tumor following postoperative radiation therapy indicated that most failures occurred out of radiation field, mostly in pleura not regional lymph nodes. Policy of target volume confined to tumor bed only seems reasonable in treating these patients although development of more effective systemic therapy regimen would be warranted.

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Phase 1 study of spinal cord constraint relaxation with single session spine stereotactic radiosurgery in the primary management of patients with inoperable, previously unirradiated metastatic epidural spinal cord compression

In this Phase 1 prospective clinical trial, spinal cord dose constraint relaxation up to 16 Gy was not associated with any myelopathy events and may be considered in high risk inoperable patients with epidural disease, or metastatic epidural spinal cord compression to optimize local control.

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Comparative effectiveness of prostate cancer treatment options: limitations of retrospective analysis of cancer registry data

Using a unique population-based dataset that includes detailed data on comorbidities and functional limitations, we compared overall survival among the "healthiest" patients with localized prostate cancer who received different treatments. Survival results differed dramatically across groups, suggesting that despite the detailed health status data, residual confounding remained. This study highlights an important limitation of studies using population-based cancer registry data, especially when comparing survival outcomes of vastly different treatment modalities.

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Large-Scale EGFR Mutation Testing in Clinical Practice: Analysis of a Series of 18,920 Non-Small Cell Lung Cancer Cases

Abstract

We make use of a very large dataset of non-small cell lung cancer specimens to examine the molecular epidemiology of EGFR mutations, particularly with respect to rare and compound mutations, and to non-adenocarcinoma histological subtypes. We also demonstrate the feasibility of large-scale EGFR mutation screening using the full range of specimens encountered in routine practice. We retrospectively reviewed 18,920 unselected EGFR mutation results from our centre between July 2009 and October 2016, using Qiagen's therascreen EGFR RGQ PCR Kit. Mutation rates were correlated with patient demographics and tumour histology. Our testing success rate was 93.9%, with similar success rates using histological and cytological specimens. Rare, potentially-targetable mutations accounted for 9.5% of all mutations detected. We identified a 2.5% mutation rate in tumours diagnosed as squamous cell carcinomas. There was a trend towards increasing EGFR mutation rates with increasing age, and while Del19 was the commonest mutation in the young, L858R predominated in the elderly. We found that EGFR mutation heterogeneity is rare within tumours and between primary and metastatic deposits. Our data demonstrate that large-scale, reflex EGFR mutation testing is feasible and affordable in the context of a publicly-funded health system. Furthermore, we have shown that the use of techniques sensitive only to classical mutations and selection of patients on the grounds of age, sex and histology denies patients access to potentially beneficial TKI therapy.

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Excessive Screen Time and Psychosocial Well-Being: The Mediating Role of Body Mass Index, Sleep Duration, and Parent-Child Interaction

To examine the relationship between excessive screen time and psychosocial well-being in preschool children, and the potential mediating role of body mass index, sleep duration, and parent-child interaction.

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Partner support during the prenatal testing period after assisted conception

Publication date: Available online 9 August 2018

Source: Women and Birth

Author(s): Joëlle Darwiche, Anne Milek, Jean-Philippe Antonietti, Yvan Vial

Abstract

Background

Pregnancy after infertility is a challenging experience. The first-trimester screening test may add stress. Partner support reduces psychological distress in pregnant women after spontaneous conception. No data are available for women who conceive via assisted reproductive technology.

Aim

To assess whether there was a difference between couples who underwent assisted reproductive technology and couples who conceived spontaneously in the support they felt they provided to their partner and whether their perception of support received from their partner reduced their distress.

Methods

This longitudinal prospective study included 52 women (spontaneous conception) and 53 women (assisted reproductive technology), as well as their partners. Participants completed the state scale of the State-Trait Anxiety Inventory, the Edinburgh Depression Scale, and two partner-support subscales of the Dyadic Coping Inventory: before prenatal testing (gestational age 12 weeks), immediately after receiving the results (gestational age of approximately 14 weeks), and once all the prenatal screenings had been completed (gestational age 22 weeks).

Findings

Women who underwent assisted reproductive technology felt less able to help their partner cope with stress and felt their partner was less able to help them cope with stress than women with spontaneous pregnancy. This difference was not observed in men. Higher perceived partner support lowered the anxiety and depression of couples who conceived spontaneously, but did not benefit couples who followed fertility treatment.

Conclusion

These results add to our knowledge of the emotional state of women and their partners during pregnancy after infertility. This knowledge may allow prenatal care providers to offer specialized counselling to women and their partners in the transition from infertility to parenthood.

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Ambulatory spine surgery: Outcomes compared to inpatient surgery

Publication date: Available online 9 August 2018

Source: Seminars in Spine Surgery

Author(s): Daniel Bu, Catherine Himo Gang, Blake Kushwaha, Sheeraz Qureshi

Abstract

The purpose of this paper is to review outcomes of ambulatory spine surgeries to its inpatient counterpart. Ambulatory spine surgeries have been on the rise as there has been evidence to support increased safety, faster healing and increased cost effectiveness with outpatient procedures. However, there has not been a paper to compare the most commonly performed outpatient spine surgery procedure outcomes with inpatient outcomes. These p+rocedures include lumbar microdiscectomy, posterior lumbar decompression, posterior cervical decompression, anterior cervical discectomy and fusion, and cervical disc replacement. Outcomes, risks, and advantages were reviewed for each type of spine surgery.

https://ift.tt/2MfEM19

A 12-Year-Old Girl with Bilateral Coats Disease and ABCA4 Gene Mutation

A 12-year-old girl with bilateral stage 2B Coats disease was screened meticulously for a possible underlying systemic disease as she was female and the disease was bilateral. Full systemic workout turned out to be unremarkable. However, an ABCA4 gene mutation was found in the genetic analysis. NDP and TINF2 gene mutations were not present. She was successfully treated with a bilateral, single intravitreal injection of dexamethasone implant and a single session of indirect laser photocoagulation with a relatively good anatomic and functional result. To the best of our knowledge, the present case is the only reported case of Coats disease with an ABCA4 gene mutation.
Case Rep Ophthalmol 2018;9:375–380

https://ift.tt/2OXEBWP

Unilateral Multifocal Intraocular Lens Implantation in a Patient with Adie’s Pupil

Purpose: To report a case of a patient with unilateral Adie's pupil who underwent bilateral cataract extraction with multifocal and monofocal posterior chamber intraocular lens (IOL) implantation. Methods: A 74-year-old woman presented to our institution complaining of worsening near vision. Gross examination revealed a 6-mm fixed pupil on the right eye (OD) and a 5-mm pupil reacting to 3 mm with light on the left eye (OS). Slit lamp examination revealed a tonic pupil with an exaggerated pupillary constriction to dilute pilocarpine OD. Dilated exam revealed 2–3+ nuclear and cortical lens changes bilaterally. The patient's active lifestyle, personality, and biometry measurements made her a good candidate for multifocal IOL (MfIOL) implantation OS. Femtosecond laser-assisted cataract extraction with a ReSTOR +3 ADD (SN60D1) implantation was performed OS. Monofocal lens implantation (SN60WF) was performed OD 6 months later. Results: One year postoperatively, our patient had an uncorrected visual acuity (VAsc) of 20/15 for distance and J10 for near OD. Her VAsc was 20/25 +1 for distance and J1 for near OS. Visual acuity when using both eyes was 20/15 for distance and J1 for near. Conclusion: Optimizing success for MfIOL implantation is a multifactorial process. Large pupils preoperatively are of particular concern, as this may lead to increased dysphotopsia with pupil-dependent MfIOLs. Thus, patients with unilateral mydriasis, such as Aide's pupil, may have a beneficial outcome combining multifocal-monofocal implantation after bilateral cataract extraction, especially if they are not a candidate for monovision but desire spectacle independence.
Case Rep Ophthalmol 2018;9:369–374

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Activating human epidermal growth factor receptor 2 ( HER2 ) gene mutation in bone metastases from breast cancer

Abstract

In addition to amplification, point mutations of the human epidermal growth factor receptor 2 (HER2) gene (ERBB2) have been shown to activate the corresponding signaling pathway in breast cancer. The prevalence of ERBB2/HER2 mutation in bone metastasis of breast cancer and the associated phenotype are not known. In this study, bone metastases from breast cancer patients (n = 231) were analyzed for ERBB2/HER2 mutation. In 7 patients (3%; median age 70 years, range 50–83 years), gain-of-function mutations of ERBB2/HER2 were detected. The most frequent mutation was p.L755S (71%). In 29% of mutated cases, p.V777L was found. Lobular breast cancer was present in 71% of mutated cases (n = 5) and in 49% of all samples (n = 231; p = 0.275). Mutation frequency was 4.4% in the lobular subgroup and 17.4% in the pleomorphic subtype of lobular cancer (n = 23), respectively. All but one mutated lobular cancers were of the pleomorphic subtype (p = 0.006). Mutated cancers belonged either to the luminal (n = 4) or to the triple-negative types (n = 3). With regard to protein expression and gene amplification, HER2 was negative in all mutated cases. Among the 14% of metastatic luminal cancers with estrogen receptor gene (ESR1) mutation, conveying resistance against aromatase inhibitors, no concomitant ERBB2/HER2 mutation occurred. We conclude that activating HER2 mutation is present in about 3% of bone metastases from breast cancers, with significantly higher rates in the pleomorphic subtype of lobular cancer. Since mutated cases appear to be HER2-negative by conventional testing, the opportunity for specific anti-HER2 therapy may be missed.

https://ift.tt/2vSDdw8

When Moral Outrage Goes Viral, It Can Come Across as Bullying

On social media, people can be quick to call attention to racist, sexist, or unpatriotic behavior they see. But when that outcry goes viral, those challenging the behavior may be perceived less as noble heroes doing the right thing and more like bullies doling out excessive punishment, according to findings published in Psychological Science, a journal of the Association for Psychological Science.

Through a series of laboratory studies, Stanford psychology Professor Benoît Monin and graduate student Takuya Sawaoka found that while comments against offensive behavior are seen as legitimate and even admirable as individual remarks, when they multiply they may lead to greater sympathy for the offender.

"One of the features of the digital age is that anyone's words or actions can go viral, whether they intend to or not," said Sawaoka. "In many cases, the social media posts that are met with viral outrage were never intended to be seen by people outside of the poster's social circle. Someone doesn't even need to be on social media in order for their actions to go viral."

Sawaoka and Monin conducted six experiments with a total of 3,377 participants to examine how people perceived public outcry to an offensive or controversial post on social media. They set up a variety of scenarios, including asking people how they felt when there were only one or two comments versus a mass of replies.

In one study, the researchers showed participants a post taken from a real story of a charity worker who posted a photograph of herself making an obscene gesture and pretending to shout next to a sign that read "Silence and Respect" at Arlington National Cemetery.

They asked participants how offensive they found the photograph, as well as what they thought about the responses to the post.

Sawaoka and Monin found that when participants saw the post with just a single comment condemning it, they found the reaction applaudable.

When they saw that reply echoed by many others, they viewed the original reply – that had been praiseworthy in isolation – more negatively. Early commenters were de facto penalized for later, independent responses, they said.

"There is a balance between sympathy and outrage," said Monin about their findings. "The outrage goes up and up but at some point sympathy kicks in. Once a comment becomes part of a group, it can appear problematic. People start to think, 'This is too much – that's enough.' We see outrage at the outrage."

The researchers were curious to know whether people would feel less sympathetic depending on the status of the offender. Would they feel differently if something offensive was said by a well-known person, or by someone many people regard as abhorrent, like a white supremacist?

Sawaoka and Monin tested for that as well.

In one study, participants were shown a social media post taken from a real story where a comedian ridiculed overweight women. The researchers set up two conditions: one where they referred to him as an average social media user, and another where they said he was an up-and-coming comedy actor.

Mirroring their earlier findings, the researchers found that a high-profile persona did not elicit any less sympathy than the average person – despite the fact that people believed they could cause more harm from their post. And like their previous results, the researchers found that individual commenters are also viewed less favorably after outrage went viral.

When Sawaoka and Monin tested for affiliation to a white supremacist organization, they found similar results. Although participants were less sympathetic toward a white supremacist making a racist comment, they did not view the individuals who participated in the outrage any differently. They still perceived the display of viral outrage as bullying.

"These results suggest that our findings are even more broadly applicable than we had originally anticipated, with viral outrage leading to more negative impressions of individual commenters even when the outrage is directed toward someone as widely despised as a white supremacist," Sawaoka and Monin wrote.

The question about how to respond to injustice in the digital age is complex, Sawaoka and Monin concluded in the paper.

There is no easy solution, the researchers said.

"Our findings illustrate a challenging moral dilemma: A collection of individually praiseworthy actions may cumulatively result in an unjust outcome. Obviously, the implication is not that people should simply stay silent about others' wrongdoing," said Sawaoka. "But I think it is worth reconsidering whether the mass shaming of specific individuals is really the best way to achieve social progress."

https://ift.tt/2OmCL0E

Targeted next-generation sequencing identifies clinically relevant somatic mutations in a large cohort of inflammatory breast cancer.

Targeted next-generation sequencing identifies clinically relevant somatic mutations in a large cohort of inflammatory breast cancer.

Breast Cancer Res. 2018 Aug 07;20(1):88

Authors: Liang X, Vacher S, Boulai A, Bernard V, Baulande S, Bohec M, Bièche I, Lerebours F, Callens C

Abstract
BACKGROUND: Inflammatory breast cancer (IBC) is the most aggressive form of primary breast cancer. Using a custom-made breast cancer gene sequencing panel, we investigated somatic mutations in IBC to better understand the genomic differences compared with non-IBC and to consider new targeted therapy in IBC patients.
METHODS: Targeted next-generation sequencing (NGS) of 91 candidate breast cancer-associated genes was performed on 156 fresh-frozen breast tumor tissues from IBC patients. Mutational profiles from 197 primary breast tumors from The Cancer Genome Atlas (TCGA) were used as non-IBC controls for comparison analysis. The mutational landscape of IBC was correlated with clinicopathological data and outcomes.
RESULTS: After genotype calling and algorithmic annotations, we identified 392 deleterious variants in IBC and 320 variants in non-IBC cohorts, respectively. IBC tumors harbored more mutations than non-IBC (2.5 per sample vs. 1.6 per sample, p < 0.0001). Eighteen mutated genes were significantly different between the two cohorts, namely TP53, CDH1, NOTCH2, MYH9, BRCA2, ERBB4, POLE, FGFR3, ROS1, NOTCH4, LAMA2, EGFR, BRCA1, TP53BP1, ESR1, THBS1, CASP8, and NOTCH1. In IBC, the most frequently mutated genes were TP53 (43.0%), PIK3CA (29.5%), MYH9 (8.3%), NOTCH2 (8.3%), BRCA2 (7.7%), ERBB4 (7.1%), FGFR3 (6.4%), POLE (6.4%), LAMA2 (5.8%), ARID1A (5.1%), NOTCH4 (5.1%), and ROS1 (5.1%). After grouping 91 genes on 10 signaling pathways, we found that the DNA repair pathway for the triple-negative breast cancer (TNBC) subgroup, the RTK/RAS/MAPK and cell cycle pathways for the HR-/HER2+ subgroup, the DNA repair, RTK/RAS/MAPK, and NOTCH pathways for the HR+/HER2- subgroup, and the DNA repair, epigenome, and diverse pathways for the HR+/HER2+ subgroup were all significantly differently altered between IBC and non-IBC. PIK3CA mutation was independently associated with worse metastasis-free survival (MFS) in IBC since the median MFS for the PIK3CA mutant type was 26.0 months and for the PIK3CA wild type was 101.1 months (p = 0.002). This association was observed in TNBC (p = 0.04) and the HR-/HER2+ subgroups (p = 0.0003), but not in the HR+/HER2- subgroup of IBC.
CONCLUSIONS: Breast cancer-specific targeted NGS uncovered a high frequency of deleterious somatic mutations in IBC, some of which may be relevant for clinical management.

PMID: 30086764 [PubMed - in process]

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Wolbachia’s role in mediating its flea's reproductive success differs according to flea origin

Abstract

Endosymbionts—microbes that live within and engage in prolonged and intimate associations with their hosts—are gaining recognition for their direct impact on plant and animal reproduction. Here we used the overlooked Wolbachia-flea system to explore the possibility that endosymbionts may also play a role as mediators in shaping the reproductive success of their hosts. We simultaneously quantified the Wolbachia density in field- and laboratory-originated fleas that fed and mated on rodents for either five or ten days and assessed their body size and current reproductive success. By combining multigroup analysis and model selection approaches, we teased apart the contribution of the direct effects of the flea's physiological age and body size and the mediation effect of its Wolbachia endosymbionts on flea reproductive success, and we showed that the latter was stronger than the former. However, interestingly, the mediation effect was manifested only in laboratory-originated fleas, for which the increase in Wolbachia with age translated into lower reproductive success. These results suggest that some well-supported phenomena, such as aging effects, may be driven by endosymbionts and show once again that the role of endosymbionts in shaping the reproductive success of their host depends on their selective environment.

https://ift.tt/2KCT3A9

Vicinal land use change strongly drives stream bacterial community in a tropical montane catchment

Abstract

Impact of land use (LU) change on stream environmental conditions and the inhabiting bacterial community remains rarely investigated, especially in tropical montane catchments. We examined the effects of LU change and its legacy along a tropical stream by comparing seasonal patterns of dissolved organic carbon (DOC)/colored dissolved organic matter (CDOM) in relation to variations in structure, diversity and metabolic capacities of particle-attached (PA) and free-living (FL) bacterial communities. We hypothesized that despite seasonal differences, hydrological flows that accumulate allochthonous carbon along the catchment are a major controlling factor of the bacterial community. Surprisingly, local environmental conditions that were largely related to nearby LU and the legacy of LU change were more important for stream bacterial diversity than hydrological connectivity. DOC was strongly correlated with PA richness and diversity. The legacy of LU change between teak plantation and annual crops induced high DOC and high diversity and richness of PA in the adjacent waters, while banana plantations were associated with high diversity of FL. The community structures of both PA and FL differed significantly between seasons. Our results highlight the importance of vicinal LU change and its legacy on aquatic bacterial communities in mixed used tropical watersheds.

https://ift.tt/2OUBNdd

Scholarly reputation

Abstract

The aim of this literature review on scholarly reputation is: (1) to clarify the concept of scholarly reputation; and (2) to identify the opportunities for scholars (and especially the early career ones among them) to build, maintain and showcase their reputation in today's increasingly open-values based, digital and networked environment. Thus, an in-depth discussion of the notion of scholarly reputation, inclusive of its multi-dimensional sub-constructs and antecedents, is followed by an attempt to establish how it is to be achieved and managed.

https://ift.tt/2OY7Atw

Bacterial type III secretion systems: A complex device for delivery of bacterial effector proteins into eukaryotic host cells

Abstract

Virulence-associated type III secretion systems serve the injection of bacterial effector proteins into eukaryotic host cells. They are able to secrete a great diversity of substrate proteins in order to modulate host cell function, and have evolved to sense host cell contact and to inject their substrates through a translocon pore in the host cell membrane. T3SS substrates contain an N-terminal signal sequence and often also a chaperone-binding domain for cognate T3SS chaperones. These signals guide the substrates to the machine where substrates are unfolded and handed over to the secretion channel formed by the transmembrane domains of the export apparatus components and by the the needle filament. Secretion itself is driven by the proton motif force across the bacterial inner membrane. The needle filament measures 20–150 nm in length and is crowned by a needle tip that mediates host cell sensing. Secretion through T3SS is a highly regulated process with early, intermediate, and late substrates. A strict secretion hierarchy is required to build an injectisome capable of reaching, sensing, and penetrating the host cell membrane, before host cell acting effector proteins are deployed. Here we review the recent progress on elucidating assembly, structure, and function of T3SS injectisomes.

https://ift.tt/2AXU06G

Mitigating the Risks of Medicaid Work Requirements

In January 2018, the Centers for Medicare and Medicaid Services (CMS) issued a letter to state Medicaid directors "to assist states in their efforts to improve Medicaid enrollee health and well-being through incentivizing work and community engagement." As of June 2018, four states — Arkansas,…

https://ift.tt/2AYczrw

Will Courts Allow States to Regulate Drug Prices?

Pharmaceuticals are consuming increasingly large portions of U.S. state budgets, and high prices are preventing patients from getting, and adhering to, essential medicines. In mid-May 2018, President Donald Trump announced a heavily hyped but relatively modest federal plan to bring down drug…

https://ift.tt/2vy0cgt

Mitigating the Risks of Medicaid Work Requirements

Revision Rates for Arthritis-Related Hip Replacement Down

THURSDAY, Aug. 9, 2018 -- Use of cross-linked polyethylene (XLPE) has significantly reduced the revision rate following total hip arthroplasty (THA) for osteoarthritis, according to a study published in the Aug. 1 issue of the Journal of Bone &...

https://ift.tt/2npRvR9

Perspectives on USPSTF A-Fib Screening Recommendation

THURSDAY, Aug. 9, 2018 -- The U.S. Preventive Service Task Force published a final recommendation on Aug. 7 citing insufficient evidence to assess the benefits and harms of screening for atrial fibrillation (AF) with electrocardiography (ECG) in...

https://ift.tt/2vPhJjG

High BP Seen at School Age for Extreme Preterm Infants

THURSDAY, Aug. 9, 2018 -- Both overweight and normal-weight children who were born as extreme preterm (EPT) infants are at risk for high blood pressure (BP) and hypertension, according to a study published in the August issue of Pediatrics. Betty R....

https://ift.tt/2nmuYnY

American Heart Association Urges Screen Time Limits for Youth

THURSDAY, Aug. 9, 2018 -- The American Heart Association (AHA) is concerned about the impact screen time is having on sedentary behavior in children and teens, according to a scientific statement published online Aug. 6 in Circulation. Tracie A....

https://ift.tt/2vPhu8g

Infection Prevention Differs Between Small, Large Hospitals

THURSDAY, Aug. 9, 2018 -- Small and large hospitals differ in infection preventionist (IP) staffing and infection prevention and control (IPC) resources, according to a study published in the August issue of the American Journal of Infection...

https://ift.tt/2nnKIHn

Few Older Homeless Adults Make Advance Care Plans

THURSDAY, Aug. 9, 2018 -- The majority of older homeless-experienced adults have a potential surrogate for health care decisions, but few have discussed or documented their advance care planning (ACP) wishes, according to a study published in the...

https://ift.tt/2vSASBk

Healthy Lifestyle With Diabetes Cuts Cardiovascular Risk

THURSDAY, Aug. 9, 2018 -- Greater adherence to an overall healthy lifestyle is associated with a substantially lower risk of cardiovascular disease (CVD) incidence and mortality among adults with type 2 diabetes (T2D), according to a study published...

https://ift.tt/2nodNTa

Insurance Status Tied to Higher Self-Perceived Poor/Fair Health

THURSDAY, Aug. 9, 2018 -- Underinsured and never insured adults are more likely than adequately insured adults to report poor/fair health and frequent mental distress (FMD), according to a study published online July 19 in the U.S. Centers for...

https://ift.tt/2vPgWze

USPSTF: Insufficient Evidence to Screen for Atrial Fibrillation

THURSDAY, Aug. 9, 2018 -- There is insufficient evidence to support screening for atrial fibrillation (AF) with electrocardiography (ECG) in older, asymptomatic patients, according to a U.S. Preventive Services Task Force (USPSTF) final...

https://ift.tt/2nodFmE

Vit D Supplementation Doesn't Improve Fetal, Infant Growth

THURSDAY, Aug. 9, 2018 -- Maternal vitamin D supplementation from mid-pregnancy until birth or until six months postpartum does not improve fetal or infant growth, according to a study published in the Aug. 9 issue of the New England Journal of...

https://ift.tt/2w0taVZ

The Utilization of Medical Devices by Traditional Korean Medicine Doctors Investigated through Traditional Korean Medicine Clinical Studies

Objective. The purpose of this study was to investigate the current status of modern medical devices utilized in diagnosis and treatment in traditional Korean medicine (TKM). Methods. We searched the following six Korean electronic databases to collect TKM clinical studies that were published in a five-year period (January 2012 to December 2016). Clinical studies of TKM when medical devices were used for diagnosis or treatment were investigated. Results. The search generated a total of 3,735 articles, and 1,328 of these were considered to be clinical studies. Of a total of 1,328 clinical studies of TKM, 774 articles (58.3%) used medical devices for diagnosis or treatment, and 554 articles (41.7%) did not use medical devices for diagnosis or treatment. The three most used diagnostic devices were as follows: MRI scanners, which were used in 194 (20.6%) studies; X-ray machines, which were used in 172 studies (18.3%); and CT scanners, which were used in 139 studies (14.8%). The three most used treatment devices were electroacupuncture equipment (20.3%), transcutaneous electrical nerve stimulation (TENS) equipment (18.4%), and interferential current therapy (ICT) equipment (16.4%). Conclusions. This study suggests that TKM doctors use diagnostic information derived from modern medical devices clinically. It is therefore necessary to institutionalize considering changes to the medical acts of traditional medicine (TM) doctors. Additionally, this information can be utilized as a reference for developing TM policy and education.

https://ift.tt/2vtuqRO

TSSC3 promotes autophagy via inactivating the Src-mediated PI3K/Akt/mTOR pathway to suppress tumorigenesis and metastasis in osteosarcoma, and predicts a favorable prognosis

Abstract

Background

Over the last two or three decades, the pace of development of treatments for osteosarcoma tends has been slow. Novel effective therapies for osteosarcoma are still lacking. Previously, we reported that tumor-suppressing STF cDNA 3 (TSSC3) functions as an imprinted tumor suppressor gene in osteosarcoma; however, the underlying mechanism by which TSSC3 suppresses the tumorigenesis and metastasis remain unclear.

Methods

We investigated the dynamic expression patterns of TSSC3 and autophagy-related proteins (autophagy related 5 (ATG5) and P62) in 33 human benign bone tumors and 58 osteosarcoma tissues using immunohistochemistry. We further investigated the correlations between TSSC3 and autophagy in osteosarcoma using western blotting and transmission electronic microscopy. CCK-8, Edu, and clone formation assays; wound healing and Transwell assays; PCR; immunohistochemistry; immunofluorescence; and western blotting were used to investigated the responses in TSSC3-overexpressing osteosarcoma cell lines, and in xenografts and metastasis in vivo models, with or without autophagy deficiency caused by chloroquine or ATG5 silencing.

Results

We found that ATG5 expression correlated positively with TSSC3 expression in human osteosarcoma tissues. We demonstrated that TSSC3 was an independent prognostic marker for overall survival in osteosarcoma, and positive ATG5 expression associated with positive TSSC3 expression suggested a favorable prognosis for patients. Then, we showed that TSSC3 overexpression enhanced autophagy via inactivating the Src-mediated PI3K/Akt/mTOR pathway in osteosarcoma. Further results suggested autophagy contributed to TSSC3-induced suppression of tumorigenesis and metastasis in osteosarcoma in vitro and in vivo models.

Conclusions

Our findings highlighted, for the first time, the importance of autophagy as an underlying mechanism in TSSC3-induced antitumor effects in osteosarcoma. We also revealed that TSSC3-associated positive ATG5 expression might be a potential predictor of favorable prognosis in patients with osteosarcoma.

https://ift.tt/2vwlqez

Prognostic outcome and complications of sentinel lymph node navigation surgery for early-stage cervical cancer

Abstract

Background

To evaluate the prognostic outcome and surgical complications in patients with early-stage cervical cancer who underwent sentinel node navigation surgery (SNNS) for hysterectomy or trachelectomy.

Methods

A total of 139 patients who underwent SNNS using ^99mTc phytate between 2009 and 2015 were evaluated. No further lymph node dissection was performed when intraoperative analysis of the sentinel lymph nodes (SLNs) was negative for metastasis. We compared the surgical complications between the SNNS group and 67 matched patients who underwent pelvic lymph node dissection (PLND) after SLN mapping between 2003 and 2008. We also examined the clinical outcomes in the SNNS group.

Results

The mean number of detected SLNs was 2.5 per patient. Fourteen of the 139 patients in the SNNS group underwent PLND based on the intraoperative SLN results. The amount of blood loss, the operative time, and the number of perioperative complications were significantly less in the SNNS group than in the matched PLND group. There was no recurrence during a follow-up period ranging from 2 to 88 months (median 40 months) in the SNNS group.

Conclusions

Using SNNS for early-stage cervical cancer is safe and effective and does not increase the recurrence rate. A future multicenter trial is warranted.

https://ift.tt/2AVDXGn

Cancer-associated MORC2 mutant M276I regulates an hnRNPM-mediated CD44 splicing switch to promote invasion and metastasis in triple-negative breast cancer

Triple-negative breast cancer (TNBC) is the most lethal subtype of breast cancer, with a high propensity for distant metastasis and limited treatment options, yet its molecular underpinnings remain largely unknown. Microrchidia family CW-type zinc finger 2 (MORC2) is a newly identified chromatin remodeling protein whose mutations have been causally implicated in several neurological disorders. Here we report that a cancer-associated substitution of methionine to isoleucine at residue 276 (M276I) of MORC2 confers gain-of-function properties in the metastatic progression of TNBC. Expression of mutant MORC2 in TNBC cells increased cell migration, invasion, and lung metastasis without affecting cell proliferation and primary tumor growth compared with its wild-type counterpart. The M276I mutation enhanced binding of MORC2 to heterogeneous nuclear ribonucleoprotein M (hnRNPM), a component of the spliceosome machinery. This interaction promoted an hnRNPM-mediated splicing switch of CD44 from the epithelial isoform (CD44v) to the mesenchymal isoform (CD44s), ultimately driving epithelial-mesenchymal transition (EMT). Knockdown of hnRNPM reduced the binding of mutant MORC2 to CD44 pre-mRNA and reversed the mutant MORC2-induced CD44 splicing switch and EMT, consequently impairing the migratory, invasive, and lung metastatic potential of mutant MORC2-expressing cells. Collectively, these findings provide the first functional evidence for the M276I mutation in promoting TNBC progression. They also establish the first mechanistic connection between MORC2 and RNA splicing and highlight the importance of deciphering unique patient-derived mutations for optimizing clinical outcomes of this highly heterogeneous disease.

https://ift.tt/2vQlUvD

Loss of MST/Hippo signaling in a genetically engineered mouse model of fusion-positive rhabdomyosarcoma accelerates tumorigenesis

A hallmark of fusion-positive alveolar rhabdomyosarcoma (aRMS) is the presence of a chromosomal translocation encoding the PAX3-FOXO1 fusion oncogene. Primary cell-based modeling experiments have shown that PAX3-FOXO1 is necessary, but not sufficient for aRMS tumorigenesis, indicating additional molecular alterations are required to initiate and sustain tumor growth. Previously we showed that PAX3-FOXO1-positive aRMS is promoted by dysregulated Hippo pathway signaling, as demonstrated by increased YAP1 expression and decreased MST activity. We hypothesized that ablating MST/Hippo signaling in a genetically engineered mouse model (GEMM) of aRMS would accelerate tumorigenesis. To this end, MST1/2-floxed (Stk3F/F;Stk4F/F) mice were crossed with a previously established aRMS GEMM driven by conditional expression of Pax3:Foxo1 from the endogenous Pax3 locus and conditional loss of Cdkn2a in Myf6 (myogenic factor 6)-expressing cells. Compared to Pax3PF/PF;Cdkn2aF/F;Myf6ICN/+ controls, Stk3F/F;Stk4F/F;Pax3PF/PF;Cdkn2aF/F;Myf6ICN/+ animals displayed accelerated tumorigenesis (p<0.0001) and increased tumor penetrance (88% vs. 27%). GEMM tumors were histologically consistent with aRMS. GEMM tumor-derived cell lines showed increased proliferation and invasion and decreased senescence and myogenic differentiation. These data suggest that loss of MST/Hippo signaling acts with Pax3:Foxo1 expression and Cdkn2a loss to promote tumorigenesis. The rapid onset and increased penetrance of tumorigenesis in this model provide a powerful tool for interrogating aRMS biology and screening novel therapeutics.

https://ift.tt/2no21bl

Inhibition of the stromal p38MAPK/MK2 pathway limits breast cancer metastases and chemotherapy-induced bone loss

The role of the stromal compartment in tumor progression is best illustrated in breast cancer bone metastases, where the stromal compartment supports tumor growth, albeit through poorly defined mechanisms. p38MAPKα is frequently expressed in tumor cells and surrounding stromal cells, and its expression levels correlate with poor prognosis. This observation led us to investigate whether inhibition of p38MAPKα could reduce breast cancer metastases in a clinically relevant model. Orally administered, small-molecule inhibitors of p38MAPKα or its downstream kinase MK2, each limited outgrowth of metastatic breast cancer cells in the bone and visceral organs. This effect was primarily mediated by inhibition of the p38MAPKα pathway within the stromal compartment. Beyond effectively limiting metastatic tumor growth, these inhibitors reduced tumor-associated and chemotherapy-induced bone loss, which is a devastating comorbidity that drastically impacts quality of life for cancer patients. These data underscore the vital role played by stromal-derived factors in tumor progression and identify the p38MAPK-MK2 pathway as a promising therapeutic target for metastatic disease and prevention of tumor-induced bone loss.

https://ift.tt/2vWd0N2

Evaluation of 1294 Female Patients with Breast Pain: A Retrospective Study

Abstract

Introduction

Mastalgia, or breast pain, is one of the most important complaints referred to outpatient clinics. The objective of this study was to evaluate the factors causing mastalgia. All patients who presented to our clinic with complaints of mastalgia were assessed along with their type of mastalgia symptoms, menopausal status, and radiology results.

Methods

A total of 3157 patients with mastalgia complaints visited our clinic between January 2015 and February 2018. Only 1294 of them were retrospectively screened. Age, sex, menopausal (premenopausal, postmenopausal) status, mastalgia type (cyclic, non-cyclic), and imaging findings of the patients were examined.

Results

The mean age was 43.8 ± 11.8 (13–86) years, with 453 (35%) patients younger than 40 years and 841 (65%) older than 40. Cyclic mastalgia was found in 207 (16%) patients, and non-cyclic mastalgia was seen in 1087 (84%) patients. A total of 786 (60.7%) patients were premenopausal, and 508 (39.3%) were postmenopausal. Mammography was used in 545 (42.1%) patients; 1190 (92.0%) women had breast ultrasonography.

Conclusion

Although breast pain is a common symptom in women who are referred to breast outpatient clinics, we concluded that patients who complain of mastalgia should not be afraid of cancer. Despite this and for reassurance, clinical imaging may be necessary to alleviate these patients' suspicions.

https://ift.tt/2KEexgh

Active study: undetected prevalence and clinical inertia in the treatment of breakthrough cancer pain (BTcP)

Abstract

An elderly patient presenting with a primary spinal multifocal intradural extramedullary pilocytic astrocytoma: a case report and review of the literature

Abstract

Background

Pilocytic astrocytoma is a low-grade central nervous system tumor most commonly seen in children. Dissemination from a primary intracranial tumor along the neuroaxis has been described at both presentation and disease progression. However, the development of an intradural extramedullary pilocytic astrocytoma independent of a primary intraparenchymal tumor in an adult patient with no history of pilocytic astrocytoma has rarely been reported.

Case presentation

A 69-year-old woman presented with progressive myelopathic symptoms and thoracic radicular pain. MRI imaging of the whole spine showed an enhancing intradural extramedullary lesion extending from the cervical cord to T11 causing cord compression. Laminectomies were performed for surgical decompression and histopathology was consistent with pilocytic astrocytoma. Complete staging was done that included imaging of the brain and cerebrospinal fluid cytology. No other tumor was found by these methods. Postoperatively the patient was treated with large field spinal radiation and concurrent chemotherapy followed by adjuvant chemotherapy. She has thus far been clinically and radiographically stable.

Conclusion

This is a rare case of an adult with multiple spinal pilocytic astrocytomas in an intradural extramedullary location, typically the result of cerebrospinal fluid dissemination of neoplastic cells from a primary intracranial tumor site (i.e. drop metastasis). No conventional primary tumor was identified in this patient, suggesting these tumors may arise from heterotopic gliomas.

https://ift.tt/2vykWEX

Cancers, Vol. 10, Pages 265: Organotypic 3D Models of the Ovarian Cancer Tumor Microenvironment

Cancers, Vol. 10, Pages 265: Organotypic 3D Models of the Ovarian Cancer Tumor Microenvironment

Cancers doi: 10.3390/cancers10080265

Authors: Karen M. Watters Preety Bajwa Hilary A. Kenny

Ovarian cancer progression involves multifaceted and variable tumor microenvironments (TMEs), from the in situ carcinoma in the fallopian tube or ovary to dissemination into the peritoneal cavity as single cells or spheroids and attachment to the mesothelial-lined surfaces of the omentum, bowel, and abdominal wall. The TME comprises the tumor vasculature and lymphatics (including endothelial cells and pericytes), in addition to mesothelial cells, fibroblasts, immune cells, adipocytes and extracellular matrix (ECM) proteins. When generating 3D models of the ovarian cancer TME, researchers must incorporate the most relevant stromal components depending on the TME in question (e.g., early or late disease). Such complexity cannot be captured by monolayer 2D culture systems. Moreover, immortalized stromal cell lines, such as mesothelial or fibroblast cell lines, do not always behave the same as primary cells whose response in functional assays may vary from donor to donor; 3D models with primary stromal cells may have more physiological relevance than those using stromal cell lines. In the current review, we discuss the latest developments in organotypic 3D models of the ovarian cancer early metastatic microenvironment. Organotypic culture models comprise two or more interacting cell types from a particular tissue. We focus on organotypic 3D models that include at least one type of primary stromal cell type in an ECM background, such as collagen or fibronectin, plus ovarian cancer cells. We provide an overview of the two most comprehensive current models—a 3D model of the omental mesothelium and a microfluidic model. We describe the cellular and non-cellular components of the models, the incorporation of mechanical forces, and how the models have been adapted and utilized in functional assays. Finally, we review a number of 3D models that do not incorporate primary stromal cells and summarize how integration of current models may be the next essential step in tackling the complexity of the different ovarian cancer TMEs.

https://ift.tt/2M93G2H

Effects of baicalin on inflammatory reaction, oxidative stress and PKDl and NF-kB protein expressions in rats with severe acute pancreatitis

Abstract Purpose: To investigate the effects of baicalin on inflammatory reaction, oxidative stress and protein kinase D1 (PKD1) and nuclear factor-kappa B (NF-κB) protein expressions in severe acute pancreatitis (SAP) rats. Methods: Sixty rats were divided into sham operation, model, and low-, medium- and high-dose baicalin group. SAP model was established in later 4 groups. The later 3 groups were injected with 0.1, 0.2 and 0.4 ml/100 g 5% baicalin injection, respectively. At 12 h, the serum SAP related indexes and inflammatory factors, peripheral blood CD3 and γδT cell percentages, wet/dry ratio and pancreas ascites volume, oxidative stress indexes and PKD1 and NF-κB protein expressions in pancreatic tissue were determined. Results: Compared with model group, in high-dose baicalin group the wet/dry ratio and ascites volume, serum amylase level, phospholipase A2 activity, TNF-α, IL-1 and IL-6 levels, and pancreatic malondialdehyde level and PKD1 and NF-κB protein expression were significantly decreased (P < 0.05), and peripheral blood CD3 and γδT cell percentages and pancreatic superoxide dismutase and glutathione peroxidase levels were significantly increased (P < 0.05). Conclusion: Baicalin can resist the inflammatory reaction and oxidative stress, and down-regulate protein kinase D1 and nuclear factor-kappa B protein expressions, thus exerting the protective effects on severe acute pancreatitis in rats.

https://ift.tt/2M8jMdq

Rectal application of argan oil improves healing of colorectal anastomosis in rats

Abstract Purpose: To investigate the possible effects of argan oil on the healing of colorectal anastomoses. Methods: I n Group 1 (sham), laparotomy was performed and the colon was mobilized. In the control (Group 2) and argan oil (Group 3) groups, colonic resection and anastomosis were applied. To the control and sham groups, 2 mL of 0.9% NaCl was administred rectally, and in the argan oil group, 2 mL/day argan oil was applied rectally for 7 days. Results: The mean bursting pressures of the argan oil and sham groups were significantly higher than the values in the control group. A significant difference was determined between the tissue hydroxyproline and prolidase levels of control group and other groups. Histopathologically, argan oil showed significant beneficial effects on colonic wound healing. In the argan oil and sham groups, the tissue malondialdehyde and fluorescent oxidation product levels were found to be lower and total sulfhydryl levels were higher than the control group. Conclusions: The rectally administered argan oil was observed to have significantly ameliorated wound healing parameters and exerted a significant antioxidant effect. This is the first study in the literature about the beneficial effects of argan oil on colorectal anastomoses.

https://ift.tt/2KEA5cD

The effects of inhaled NO on plasma vasoactive factor and CTnI level in rabbits with acute massive pulmonary embolism

Abstract Purpose: To investigate changes in the plasma concentrations of cardiac troponin I (CTnI), thromboxane A2 (TXA2), prostaglandin I2 (PGI2) and endothelin-1 (ET-1) in rabbits with massive pulmonary embolism (AMPE) and the impact of nitric oxide inhalation (NOI) on these indices. Methods: A total of 30 Japanese rabbits were used to construct an MPE model and were divided into 3 groups equally (n=10), including an EXP group (undergoing modeling alone), an NOI group (receiving NOI 2 h post-modeling) and a CON group (receiving intravenous physiological saline). Results: In the model group, plasma concentration of CTnI peaked at 16 h following modeling (0.46±0.10 µg/ml) and significantly decreased following NOI. Plasma levels of TXB2, PGI2 and ET-1 peaked at 12, 16 and 8 h following modeling, respectively, and significantly decreased at different time points (0, 2, 4, 8, 12, 16, 20 and 24 h) following NOI. A significant correlation was observed between the peak plasma CTnI concentration and peak TXB2, 6-keto prostaglandin F1α and ET-1 concentrations in the model and NOI groups. Conclusion: Increases in plasma TXA2, PGI2 and ET-1 levels causes myocardial damage in a rabbit model of AMPE; however, NOI effectively down regulates the plasma concentration of these molecules to produce a myocardial-protective effect.

https://ift.tt/2M8jFP2

Cardioprotective effect of preconditioning is more efficient than postconditioning in rats submitted to cardiac ischemia and reperfusion

Abstract Purpose: To investigate the cardioprotective effects of ischemic preconditioning (preIC) and postconditioning (postIC) in animal model of cardiac ischemia/reperfusion. Methods: Adult rats were submitted to protocol of cardiac ischemia/reperfusion (I/R) and randomized into three experimental groups: cardiac I/R (n=33), preCI + cardiac I/R (n=7) and postCI + cardiac I/R (n=8). After this I/R protocol, the incidence of ventricular arrhythmia (VA), atrioventricular block (AVB) and lethality (LET) was evaluated using the electrocardiogram (ECG) analysis. Results: After reestablishment of coronary blood flow, we observed variations of the ECG trace with increased incidence of ventricular arrhythmia (VA) (85%), atrioventricular block (AVB) (79%), and increase of lethality (70%) in cardiac I/R group. The comparison between I/R + preIC group with I/R group demonstrated significant reduction in VA incidence to 28%, AVB to 0% and lethality to 14%. The comparison of I/R + postIC group with I/R group was observed significance reduction in AVB incidence to 25% and lethality to 25%. Conclusion: The preconditioning strategies produce cardioprotection more efficient that postconditioning against myocardial dysfunctions and lethality by cardiac ischemia and reperfusion.

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Is the early or delayed remote ischemic preconditioning the more effective from a microcirculatory and histological point of view in a rat model of partial liver ischemia-reperfusion?

Abstract Purpose: To compare early- and late-effect remote ischemic preconditioning (RIPC) by analysing the microcirculatory, hemodynamic and histological changes in partial liver ischemia-reperfusion of rats. Methods: 60-minute partial liver ischemia followed by 120-minute reperfusion was performed without (Control group, n=7) or with preconditioning. In RIPC groups a tourniquet was applied around the left thigh using 3 cycles of 10-minute ischemia/10-minute reperfusion, one (RIPC-1, n=7) or twenty-four hours (RIPC-24, n=7) before I/R. Hemodynamic and microcirculatory measurements were performed before and after ischemia and in 30th, 60th and 120th minute of reperfusion and histological examination at the end of reperfusion. Results: Blood pressure decreased in all groups followed by biphasic changes in Control group. In RIPC groups R120 values returned almost to normal. Heart rate increased in Control and RIPC-1 groups at R120, while RIPC-24 did not show significant changes. Microcirculation of non-ischemic liver stayed constant in Control and showed significant changes in RIPC-24 group, while in ischemic liver elevated by R120 in all groups. RIPC didn't reduce histological alterations. Conclusion: Considering the survival and the results, both remote ischemic preconditioning protocols had beneficial effect in hepatic ischemia-reperfusion, however the histopathological findings were controversial.

https://ift.tt/2M9jSla

Gastroprotective and antioxidant effects of Eremurus spectabilis Bieb. methanol extract and its isolated component isoorientin on indomethacin induced gastric ulcers in rats

Abstract Purpose: To investigate the gastroprotective effect of methanol extract of E. spectabilis and its major component isoorientin. Methods: Effects of isoorientin and methanol extract of E. spectabilis were investigated in indomethacin-induced gastric damage model on rats. Famotidine was used as the standard antiulcer drug. Numerical density of ulcer areas and oxidative status were determined on stomach tissues of rats. Results: All doses of isoorientin and methanol extract decreased MDA level and increased SOD activity and GSH levels in the stomach tissue of rats. When numerical density of ulcer areas were analized, the 500 mg/kg dose of methanol extract (84%) exhibited a similar effect to 20 mg/kg dose of standart drug famotidine (87%). Conclusions: The gastroprotective effects of E. spectabilis and its major constituent isoorientin in rats for the first time. Detailed analyses suggested that potential antioxidant activity of both plant extract and isoorientin mediates the gastroprotective effect.

https://ift.tt/2OrFFkX

NF-kB mediated CX3CL1 activation in the dorsal root ganglion contributes to the maintenance of neuropathic pain induced in adult male Sprague Dawley rats

Abstract Purpose: To evaluate the role of CX3CL1 and NF-κB in the lumbar disc herniation induced neuropathic pain. Methods: After LDH induced by implantation of autologous nucleus pulposus (NP) on the left L5 nerve root was established, mechanical thresholds and thermal hyperalgesia were tested at relevant time points during an observation period of 28 days. Expression of CX3CL1 and NF-κBin the dorsal root ganglion (DRG) were performed by using Western blotting and RT-PCR. Results: Implantation of autologous nucleus pulposus (NP) induced neuropathic pain, associated with increased mRNA and protein expression of CX3CL1 in the DRG. Moreover, intrathecal injection of neutralizing antibody against CX3CL1 could attenuates LDH-induced persistent pain hypersensitivity. Interestingly, NF-κB activation in the DRGs were found in LDH-induced neuropathic pain. Furthermore, NF-κB downregulation by p65 inhibitor PDTC markedly alleviated LDH-induced mechanical allodynia and thermal hyperalgesia in rat. Importantly, CX3CL1 neutralizing antibody (10 μg/10 μl, i.t.) reduces p-p65 protein level in DRG Conclusions: CX3XL1 could regulate LDH-induced neuropathic pain through NF-κB pathway. Targeting CX3CL1 and NF-κB may represent a potential treatment for neuropathic pain caused by LDH.

https://ift.tt/2M8k3wY

Immunoexpression of vascular endothelial growth factor and B-cell lymphoma 2 in the uterine tissue of rats treated with melatonin in the estrus phase

Abstract Purpose: To investigate the effect of melatonin on uterine tissue in the ovariectomized rat model. Methods: Fourty Wistar albino rats were divided into four groups for histologic and immunohistochemical examination. The rats were first numbered randomly and then randomly divided into 4 equal groups: control (group 1), torsion (group 2), torsion+detorsion (group 3) and torsion+detorsion+melatonin (group 4) groups. In addition, four Wistar albino rats were used for western blot analysis in each group. And also, malondialdehyde (MDA) levels were measured biochemically in all rats. Results: The histopathological examination of the uterine tissue in rats ovarectomized showed a degeneration in uterine glands, dilation of blood vessels in the internal layer with a thrombosis and bleeding, abnormal nucleuses and vacuolated cytoplasm above and below the nucleus. In torsion group, the apoptotic cells increased in luminal epithelium and gland cells. In the melatonin group showed that the Bcl2 negative effect on the uterine epithelium and did not lead to apoptotic cells. Conclusion: The increase in vascular endothelial growth factor expression resulted in the rearrangement of endothelial cell growth and the induction of angiogenesis.

https://ift.tt/2KHDmI6

Immunhistochemical analysis of Nuclear Factor Kappa Beta expression in etiopathogenesis of ovarian tumors

Abstract Purpose: To investigate the place of the transcription factor nuclear kappa B (NF-kB), which is a marker of chronic inflammation, in the etiology of the ovarian carcinoma. Methods: NFkB analysis with the immunohistochemical method has been performed. To evaluate immunohistochemical NF-kB expression in the ovarian tissue, the H-score method. H-score = ∑ Pi (i+1), where ''Pi'' is the percentage of stained cells in each intensity category (0-100%) and ''i'' is the intensity indicating weak (i=1), moderate (i=2) or strong staining (i=3). Results: It has been seen that, the mean H score is statistically significantly higher in the patient group with serous and musinous adenocarcinoma diagnosis than the two other patient groups (p<0.005). Conclusions: Factor nuclear kappa B is an important mediator that acts in the chronic inflammation. The highest expression rates are determined by the immunohistochemical method in the ovarian cancer group.

https://ift.tt/2M8jnaU

Erratum

Are urban vertebrates city specialists, artificial habitat exploiters or environmental generalists?

Synopsis

Although urbanization is a major threat to biodiversity, some species are able to thrive in cities. This might be because they have specific adaptations to urban conditions, because they are able to cope with artificial habitats in general or because they are generalists that can live in a wide range of conditions. We use the latest version of the IUCN database to distinguish these possibilities in 25,985 species of the four classes of terrestrial vertebrates with the help of phylogenetically controlled methods. We first compare species occurrence in cities with that of the five other artificial habitats recognized by the IUCN and use principal components analyses to ask which of these most resembles cities. We then test whether urban species have a wider habitat breadth than species occurring in other, non-urban, artificial habitats, as well as species that occur only in natural habitats. Our results suggest that the proportion of terrestrial vertebrates that occur in urban environments is small and that, among the species that do occur in cities, the great majority also occur in other artificial habitats. Our data also show that the presence of terrestrial vertebrates in urban habitats is skewed in favor of habitat generalists. In birds and mammals, species occurrence in urban areas is most similar to that of rural gardens, while in reptiles and amphibians, urban areas most resemble pasture and arable land. Our study suggests that cities are likely not unique, as is often thought, and may resemble other types of artificial environments, which urban exploiters can adapt to because of their wide habitat breadth.

https://ift.tt/2OX91sv

Report from the ASCO 2018 Congress, Chicago, June 1st-5th, 2018

https://ift.tt/2AU0Hqh

Distinct Bone Marrow Sources of Pleiotrophin Control Hematopoietic Stem Cell Maintenance and Regeneration

Himburg et al. demonstrate dichotomous regulation of blood stem cell maintenance and regeneration by BM stromal cells and ECs. Utilizing conditional genetic models, the authors show that blood stem cell maintenance requires PTN secretion by BM stromal cells, whereas blood stem cell regeneration requires complementary PTN production by BMECs.

https://ift.tt/2OkXBxt

Phospho-regulation of ATOH1 Is Required for Plasticity of Secretory Progenitors and Tissue Regeneration

Tomic et al. report that multisite phosphorylation of ATOH1 regulates the contribution of secretory progenitors to stem cell self-renewal in the small intestine and colon. With damage, the enhanced role of Atoh1+ progenitors in mediating tissue repair is ablated in mice expressing phosphomutant ATOH1 and overall tissue regeneration is impaired.

https://ift.tt/2McYif0

Tbx6 Induces Nascent Mesoderm from Pluripotent Stem Cells and Temporally Controls Cardiac versus Somite Lineage Diversification

Sadahiro et al. show that Tbx6 is critical for mesoderm induction and subsequent lineage diversification from pluripotent stem cells (PSCs). Transient Tbx6 expression induced nascent mesoderm and cardiovascular lineages from mouse and human PSCs, whereas prolonged Tbx6 expression suppressed cardiac differentiation and induced somite lineages, including skeletal muscle and chondrocytes.

https://ift.tt/2MxIAI8

Breast ultrasound: recommendations for information to women and referring physicians by the European Society of Breast Imaging

Abstract

This article summarises the information that should be provided to women and referring physicians about breast ultrasound (US). After explaining the physical principles, technical procedure and safety of US, information is given about its ability to make a correct diagnosis, depending on the setting in which it is applied. The following definite indications for breast US in female subjects are proposed: palpable lump; axillary adenopathy; first diagnostic approach for clinical abnormalities under 40 and in pregnant or lactating women; suspicious abnormalities at mammography or magnetic resonance imaging (MRI); suspicious nipple discharge; recent nipple inversion; skin retraction; breast inflammation; abnormalities in the area of the surgical scar after breast conserving surgery or mastectomy; abnormalities in the presence of breast implants; screening high-risk women, especially when MRI is not performed; loco-regional staging of a known breast cancer, when MRI is not performed; guidance for percutaneous interventions (needle biopsy, pre-surgical localisation, fluid collection drainage); monitoring patients with breast cancer receiving neo-adjuvant therapy, when MRI is not performed. Possible indications such as supplemental screening after mammography for women aged 40–74 with dense breasts are also listed. Moreover, inappropriate indications include screening for breast cancer as a stand-alone alternative to mammography. The structure and organisation of the breast US report and of classification systems such as the BI-RADS and consequent management recommendations are illustrated. Information about additional or new US technologies (colour-Doppler, elastography, and automated whole breast US) is also provided. Finally, five frequently asked questions are answered.

Teaching Points

• US is an established tool for suspected cancers at all ages and also the method of choice under 40.

• For US-visible suspicious lesions, US-guided biopsy is preferred, even for palpable findings.

• High-risk women can be screened with US, especially when MRI cannot be performed.

• Supplemental US increases cancer detection but also false positives, biopsy rate and follow-up exams.

• Breast US is inappropriate as a stand-alone screening method.

https://ift.tt/2vQ8qQx

Hydatid cyst of the neck mimicking a branchial cleft cyst

Here we report a rare case of primary hydatid cyst with involvement of soft tissue of the neck in a child. A 4-year-old girl presented with gradual swelling of the right side of her neck over a period of several months. The lump was fairly soft and painless with no significant inflammation. There was no other abnormal finding in the physical examination. Imaging was performed by ultrasonography followed by neck CT scan which demonstrated a simple cyst as the cause for the neck bulging. With the presumed diagnosis of a branchial cleft cyst, surgical resection was performed. Hydatid cyst was confirmed in pathology. Isolated soft-tissue hydatid cyst is an uncommon finding which should be considered in the differential diagnosis of soft-tissue cystic lesions especially in endemic regions. This is of more significance in children in whom congenital cysts of head and neck are more common.

https://ift.tt/2Mg1s1e

Non-invasive treatment of pyogenic granuloma by using Nd:YAG laser

Pyogenic granuloma is a 'reactive lesion' in the oral cavity caused due to hormonal imbalance or poor oral hygiene. There are different methods to excise this lesion but most successful is treatment with lasers. Currently, there are different lasers available commercially and are used by clinicians to excise this lesion. In this case report, a 20-year-old female patient reported to the department with a complaint of overgrowth of gingiva on lower canine. It was excised by using neodymium-doped yttrium aluminium garnet laser and the patient was asked for regular follow-up after 1 week and 6 months. The excised lesion was sent to pathology where the lesion was confirmed to be pyogenic granuloma. The patient reported no pain, no blood loss during or postsurgery. Laser is a useful technique for excisional surgeries; it is safe, effective and reduces time of treatment as well as time of healing.

https://ift.tt/2MxFgg8

Acupuncture treatment for dysfunctional uterine bleeding in an adolescent

A 17-year-old girl with a history of dysfunctional uterine bleeding (DUB) and severe dysmenorrhoea was treated with different conventional hormonal therapies for 16 months without improvement.

Treatment with traditional Chinese acupuncture was started while she was taking oral contraceptives. She received a total of 27 treatments in 17 weeks. Her menstrual cycle normalised after 4 weeks (10 treatments). She continued to be regular during the rest of treatments and to date, 6 months after the treatment was discontinued. This report summarises the acupuncture treatment for DUB in this adolescent girl.

https://ift.tt/2OXyCBg

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Πέμπτη 9 Αυγούστου 2018

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