Πέμπτη 1 Φεβρουαρίου 2018
Laser ablation is effective for temporal lobe epilepsy with and without mesial temporal sclerosis if hippocampal seizure onsets are localized by stereoelectroencephalography
Summary
Objective
Selective laser amygdalohippocampotomy (SLAH) using magnetic resonance–guided laser interstitial thermal therapy (MRgLITT) is emerging as a treatment option for drug-resistant mesial temporal lobe epilepsy (MTLE). SLAH is less invasive than open resection, but there are limited series reporting its safety and efficacy, particularly in patients without clear evidence of mesial temporal sclerosis (MTS).
Methods
We report seizure outcomes and complications in our first 30 patients who underwent SLAH for drug-resistant MTLE between January 2013 and December 2016. We compare patients who required stereoelectroencephalography (SEEG) to confirm mesial temporal onset with those treated based on imaging evidence of MTS.
Results
Twelve patients with SEEG-confirmed, non-MTS MTLE and 18 patients with MRI-confirmed MTS underwent SLAH. MTS patients were older (median age 50 vs 30 years) and had longer standing epilepsy (median 40.5 vs 5.5 years) than non-MTS patients. Engel class I seizure freedom was achieved in 7 of 12 non-MTS patients (58%, 95% confidence interval [CI] 30%-86%) and 10 of 18 MTS patients (56%, 95% CI 33%-79%), with no significant difference between groups (odds ratio [OR] 1.12, 95% CI 0.26-4.91, P = .88). Length of stay was 1 day for most patients (range 0-3 days). Procedural complications were rare and without long-term sequelae.
Significance
We report similar rates of seizure freedom following SLAH in patients with MTS and SEEG-confirmed, non-MTS MTLE. Consistent with early literature, these rates are slightly lower than typically observed with surgical resection (60%-80%). However, SLAH is less invasive than open surgery, with shorter hospital stays and recovery, and severe procedural complications are rare. SLAH may be a reasonable first-line surgical option for patients with both MTS and SEEG confirmed, non-MTS MTLE.
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A novel tubulin inhibitor STK899704 induces tumor regression in DMBA/TPA induced skin carcinogenesis model
Abstract
Skin cancer is the most common type of cancer. The incidence rate of skin cancer has continuously increased over the past decades. In an effort to discover novel anticancer agents, we identified a novel tubulin inhibitor STK899704 which is structurally distinct from other microtubule-binding agents such as colchicine, vinca alkaloids, and taxanes. STK899704 inhibited microtubule polymerization leading to mitotic arrest, and suppressed the proliferation of various cancer cell lines as well as multidrug-resistance cancer cell lines. In this study, our investigation is further extended into animal model to evaluate the effect of STK899704 on skin carcinogenesis in vivo. Surprisingly, almost 80% of the tumors treated with STK899704 were regressed with a one fifth reduction in tumor volume. Furthermore, the efficacy of STK899704 was nearly two times higher than that of 5-fluorouracil, a widely used skin cancer therapeutic. Overall, our results suggest that STK899704 is a promising anticancer chemotherapeutic that may replace existing therapies, particularly for skin cancer.
This article is protected by copyright. All rights reserved.
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Eicosapentaenoic acid ethyl ester ameliorates atopic dermatitis-like symptoms in special diet-fed hairless mice, partly by restoring covalently bound ceramides in the stratum corneum
Abstract
Skin barrier dysfunction has a key role in the development of atopic dermatitis (AD). Covalently bound ceramides (Cer), which are essential lipids for permeability barrier homeostasis, are reportedly decreased in the stratum corneum (SC) of AD patients. Hairless mice fed a special diet develop pruritic dermatitis resembling human AD. Our previous study found that oral administration of the n-3 polyunsaturated fatty acid α-linolenic acid ameliorated skin barrier dysfunction in AD mice with concomitant increase in serum eicosapentaenoic acid (EPA). In this study, we examined the effects of EPA ethyl ester (EPA-E) on diet-induced AD in hairless mice. Oral administration of EPA-E ameliorated skin barrier dysfunction and pruritus in AD mice. In the SC of AD mice, covalently bound Cer were markedly diminished. EPA-E administration restored the lack of bound Cer. Our findings imply the possible therapeutic clinical application of EPA-E in the treatment of human AD.
This article is protected by copyright. All rights reserved.
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An efficient method for eccrine gland isolation from human scalp
Abstract
We describe a simple and efficient method to isolate eccrine sweat glands from the human scalp. This method is inspired by the hair graft harvesting method used in hair transplantation. Based on the recently described anatomical relationship between the scalp hair follicle and the eccrine gland, we have found that scalp follicular unit grafts are an excellent eccrine gland isolation source, especially for the coiled component. In order to make the gland visible for stereoscopic microdissection, the follicular units need to be previously stained with a vital dye like Methylene Blue or Neutral Red. The simplicity and efficiency of this isolation method should encourage further research into human eccrine sweat gland function which has always been hindered by the difficulty of gland isolation.
This article is protected by copyright. All rights reserved.
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Case report: Calcium pyrophosphate dihydrate deposition of the temporomandibular joint diagnosed by fine-needle aspiration cytology
Calcium pyrophosphate dihydrate deposition (CPDD) is the accepted name for a disease that mainly occurs in elderly patients. This disease affects many joints in particular the knee joint. CPDD is extremely rare in the temporomandibular joint (TMJ) with only few cases reported in the English literature. Herein, we present a case of an 89 years old woman with a radiological diagnosis of chondrosarcoma of TMJ. Fine-needle aspiration cytology however showed crystals, multinucleated giant cells and macrophages which allowed a correct diagnosis of CPDD.
http://ift.tt/2FCwzxn
Phase II trial of combination treatment with paclitaxel, carboplatin and cetuximab (PCE) as first-line treatment in patients with recurrent and/or metastatic squamous cell carcinoma of the head and neck (CSPOR-HN02)
Abstract
Background
The standard of care for first-line treatment of recurrent and/or metastatic squamous cell carcinoma of the head and neck (R/M SCCHN) is combination treatment with platinum, 5-FU and cetuximab (PFE). However, this regimen requires hospitalization to ensure proper hydration and continuous infusion of 5-FU, and causes severe nausea and anorexia. We evaluated the efficacy and safety of paclitaxel, carboplatin and cetuximab (PCE) as first-line treatment in patients with R/M SCCHN. Patients and methods
Eligibility criteria included recurrent and/or metastatic, histologically proven SCC of the oropharynx, oral cavity, hypopharynx or larynx; PS 0-1; adequate organ function; no suitable local therapy for R/M SCCHN; and no prior systemic chemotherapy for R/M SCCHN. Chemotherapy consisted of paclitaxel 100mg/m2 on days 1, 8; carboplatin AUC 2.5 on days 1, 8, repeated every 3 weeks for up to 6 cycles; and cetuximab at an initial dose of 400mg/m2, followed by 250mg/m2 weekly until disease progression or unacceptable toxicities. Primary endpoint was overall response rate (ORR). Secondary endpoints were safety, treatment completion rate, progression-free survival, overall survival, and clinical benefit rate. Planned sample size was 45 patients. Results
Forty-seven subjects were accrued from July 2013 to Oct 2014. Of 45 evaluable, 40 were male; median age was 63 years; ECOG PS was 0/1 in 23/22 cases; site was the hypopharynx/oropharynx/oral cavity/larynx in 17/11/10/7 cases; and 36/9 cases were smokers/non-smokers, respectively. ORR, the primary end point, was 40%. Median overall survival was 14.7 months and progression-free survival was 5.2 months. Grade 3/4 adverse events included neutropenia (68%), skin reaction (15%), fatigue (9%) and febrile neutropenia (9%). A potentially treatment-related death occurred in one patient with intestinal pneumonia. Conclusions
The PCE regimen shows promising activity with acceptable toxicity in the outpatient clinic. Further studies are needed to compare PCE with PFE in this population. Registered clinical trial numbers
UMIN000010507http://ift.tt/2BNuHiY
Impact of genomic alterations on lapatinib treatment outcome and cell-free genomic landscape during HER2 therapy in HER2-positive gastric cancer patients
Abstract
Background
To identify predictive markers for responders in lapatinib-treated patients and to demonstrate molecular changes during lapatinib treatment via cell-free genomics. Patients and Methods
We prospectively evaluated the efficacy of combining lapatinib with capecitabine and oxaliplatin as first line neoadjuvant therapy in patients with previously untreated, HER2-overexpressing advanced gastric cancer (AGC). A parallel biomarker study was conducted by simultaneously performing immunohistochemistry (IHC) and next-generation sequencing with tumor and blood samples. Results
Complete response (CR) was confirmed in 7/32 patients (21.8%), 2 of whom received radical surgery with pathologic-confirmed CR. Fifteen partial responses (46.8%) were observed, resulting in a 68.6% overall response rate. Next-generation sequencing (NGS) of the 16 tumor specimens demonstrated that the most common co-occurring copy number alteration was CCNE1 amplification, which was present in 40% of HER2-positive tumors. The relationship between CCNE1 amplification and lack of response to HER2 targeted therapy trended toward statistical significance (66.7% of non-responders versus 22.2% of responders harbored CCNE1 amplification; p = 0.08). Patients with high level ERBB2 amplification by NGS were more likely to respond to therapy, compared to patients with low level ERBB2 amplification (p = 0.02). Analysis of cfDNA showed that detectable ERBB2 copy number amplification in plasma was predictive to the response (100%, response rate) and changes in plasma-detected genomic alterations were associated with lapatinib sensitivity and/or resistance. The follow-up cfDNA genomics at disease progression demonstrated that there are emergences of other genomic aberrations such as MYC, EGFR, FGFR2 and MET amplifications. Conclusions
The present study showed that HER2+ GC patients respond differently according to concomitant genomic aberrations beyond ERBB2, high ERBB2 amplification by NGS or cfDNA can be a positive predictor for patient selection, and tumor genomic alterations change significantly during targeted agent therapy.http://ift.tt/2nyCltl
CHILD syndrome: A modified pathogenesis-targeted therapeutic approach
Congenital Hemidysplasia with Ichthyosiform nevus and Limb Defects (CHILD syndrome) is a rare X-linked dominant genodermatosis caused by mutations in the NAD(P) dependent steroid dehydrogenase-like protein gene. Its defect leads to accumulation of toxic metabolic intermediates upstream from the pathway block and to the deficiency of bulk cholesterol, probably leading to altered keratinocyte membrane function, resulting in the phenotype seen in CHILD syndrome. Symptomatic treatment using emollients and retinoids to reduce scaling has long been used until recently, whereby new therapeutic means based on the pathogenesis-targeted therapy have been developed. We subsequently chose to use the same pathogenesis-based therapy using a 2% cholesterol and 2% lovastatin cream with or without glycolic acid in two of our patients. Improvement in CHILD skin lesions was seen as early as 4 weeks after initiation. The addition of glycolic acid helped improve the penetrance of the cholesterol and lovastatin cream into the thick waxy scales. Our study confirms the efficacy of the pathogenesis-targeted therapy and introduces the possibility of modifying its formula by adding glycolic acid in order to improve the treatment.
http://ift.tt/2DUufRR
Cover Image
The cover image, by C. Hedberg-Oldfors et al., is based on the Original Article Polyglucosan myopathy and functional characterization of a novel GYG1 mutation, DOI: 10.1111/ane.12865.
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Development of a 99mTc-Labeled CXCR4 Antagonist Derivative as a New Tumor Radiotracer
Cancer Biotherapy & Radiopharmaceuticals , Vol. 0, No. 0.
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A Decision-Analytic Model to Assess the Cost-Effectiveness of Etelcalcetide vs. Cinacalcet
Abstract
Introduction
Etelcalcetide is a novel intravenous calcimimetic for the treatment of secondary hyperparathyroidism (SHPT) in haemodialysis patients. The clinical efficacy and safety of etelcalcetide (in addition to phosphate binders and vitamin D and/or analogues [PB/VD]) was evaluated in three phase III studies, including two placebo-controlled trials and a head-to-head study versus the oral calcimimetic cinacalcet.
Objective
The objective of this study was to develop a decision-analytic model for economic evaluation of etelcalcetide compared with cinacalcet.
Methods
We developed a life-time Markov model including potential treatment effects on mortality, cardiovascular events, fractures, and subjects' persistence. Long-term efficacy of etelcalcetide was extrapolated from the reduction in parathyroid hormone (PTH) in the phase III trials and the available data from the outcomes study in cinacalcet (EVOLVE trial). Etelcalcetide was compared with cinacalcet, both in addition to PB/VD. We applied unit costs averaged from five European countries and a range of potential etelcalcetide pricing options assuming parity price to weekly use of cinacalcet and varying it by a 15 or 30% increase.
Results
Compared with cinacalcet, the incremental cost-effectiveness ratio of etelcalcetide was €1,355 per QALY, €24,521 per QALY, and €47,687 per QALY for the three prices explored. The results were robust across the probabilistic and deterministic sensitivity analyses.
Conclusions
Our modelling approach enabled cost-utility assessment of the novel therapy for SHPT based on the observed and extrapolated data. This model can be used for local adaptations in the context of reimbursement assessment.
http://ift.tt/2EyaReE
Human Embryonic Kidney 293 Cells: A Vehicle for Biopharmaceutical Manufacturing, Structural Biology, and Electrophysiology
Mammalian cells, e.g., CHO, BHK, HEK293, HT-1080, and NS0 cells, represent important manufacturing platforms in bioengineering. They are widely used for the production of recombinant therapeutic proteins, vaccines, anticancer agents, and other clinically relevant drugs. HEK293 (human embryonic kidney 293) cells and their derived cell lines provide an attractive heterologous system for the development of recombinant proteins or adenovirus productions, not least due to their human-like posttranslational modification of protein molecules to provide the desired biological activity. Secondly, they also exhibit high transfection efficiency yielding high-quality recombinant proteins. They are easy to maintain and express with high fidelity membrane proteins, such as ion channels and transporters, and thus are attractive for structural biology and electrophysiology studies. In this article, we review the literature on HEK293 cells regarding their origins but also stress their advancements into the different cell lines engineered and discuss some significant aspects which make them versatile systems for biopharmaceutical manufacturing, drug screening, structural biology research, and electrophysiology applications.
Cells Tissues Organs
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MicroRNA-1246 is an exosomal biomarker for aggressive prostate cancer
Due to high heterogeneity, molecular characterization of prostate cancer (PCa) based on biopsy sampling is often challenging. Hence, a minimally invasive method to determine the molecular imprints of a patient's tumor for risk stratification would be advantageous. In this study, we employ a novel, digital amplification-free quantification method using the nCounter technology (Nanostring Technologies) to profile exosomal serum miRNAs (ex-miRNA) from aggressive PCa cases, benign prostatic hyperplasia (BPH), and disease-free controls. We identified several dysregulated miRNAs, one of which was the tumor suppressor miR-1246. miR-1246 was downregulated in PCa clinical tissues and cell lines and was selectively released into exosomes. Overexpression of miR-1246 in a PCa cell line significantly inhibited xenograft tumor growth in vivo and increased apoptosis and decreased proliferation, invasiveness, and migration in vitro. miR-1246 inhibited N-cadherin and vimentin activities, thereby inhibiting epithelial-mesenchymal transition. Ex-miR-1246 expression correlated with increasing pathological grade, positive metastasis, and poor prognosis. Our analyses suggest ex-miR-1246 as a promising PCa biomarker with diagnostic potential that can predict disease aggressiveness.
http://ift.tt/2GFg3ha
Antimicrobial susceptibility pattern, and associated factors of Salmonella and Shigella infections among under five children in Arba Minch, South Ethiopia
Diarrheal diseases continue to be the major cause of morbidity and mortality among children under 5 years. Salmonella and Shigella specious are the major enteric pathogen causing diarrhea among children worldwide...
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Early Electroencephalography Findings in Cardiogenic Shock Patients Treated by Venoarterial Extracorporeal Membrane Oxygenation
Objectives: We aimed to assess early electroencephalography findings in patients treated by venoarterial extracorporeal membrane oxygenation and their association with neurologic outcome. Design: Single-center observational study. Setting: Medical ICU of a university hospital. Patients: An early standardized electroencephalography assessment, that is, standard electroencephalography followed by continuous electroencephalography, was performed in consecutive cardiogenic shock patients requiring venoarterial extracorporeal membrane oxygenation. Associations between electroencephalography findings and outcome, defined as a composite of acute brain injury or death at 14 days, were investigated. Measurements and Main Results: Twenty-two patients with a median Full Outline of Unresponsiveness score of 4 (interquartile range, 3–6) were studied. Pupillary light reflex, corneal reflex, and cough reflex were preserved in 20 (90%), 17 (77%), and 17 (77%) patients, respectively. Overall, standard electroencephalography findings consisted of diffuse slowing in 21 patients (95%) and severe background abnormalities in 13 patients (59%) (i.e., a discontinuous [n = 5; 23%] and/or an unreactive background [n = 9; 41%]). Severe background abnormalities on standard electroencephalography (poor outcome rate: 69% vs 22%; p = 0.03) and absence of sleep transients on continuous electroencephalography (poor outcome rate: 67% vs 14%; p = 0.02) were associated with a poor outcome, whereas neurologic findings and doses of sedation were not. Patients without sleep transients on continuous electroencephalography tended to have lower Full Outline of Unresponsiveness scores than patients with preserved sleep transients-appearing patterns. Conclusions: In patients treated by venoarterial extracorporeal membrane oxygenation, early severe background abnormalities on standard electroencephalography provide important information on neurologic outcome. The lack of sleep transients on continuous electroencephalography reflects the severity of brain dysfunction and might represent an additional prognostic marker. Supplemental digital content is available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal's website (http://ift.tt/29S62lw). Dr. Dalloz received funding from UCB. Dr. Timsit received funding from 3M, Paratek, Merck; funding for speaker bureaus from Bayer; and funding for research grants from Pfizer and Astelas. Dr. d'Ortho's institution received funding from ResMed (SERVE HF, FACE, ORCADES studies) and JAZZ Pharmaceuticals; she received funding from Philips; funding for lectures from Elivie, Sanofi, Sorin, and Vitalaire; and funding for travel support from Vitalaire, UCB, Oxyvie. The remaining authors have disclosed that they do not have any potential conflicts of interest. For information regarding this article, E-mail: romain.sonneville@aphp.fr Copyright © by 2018 by the Society of Critical Care Medicine and Wolters Kluwer Health, Inc. All Rights Reserved.
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Radiomics as a Quantitative Imaging Biomarker: Practical Considerations and the Current Standpoint in Neuro-oncologic Studies
Abstract
Radiomics utilizes high-dimensional imaging data to discover the association with diagnostic, prognostic, predictive endpoint or radiogenomics. It is an emerging field of study that potentially depicts the intratumoral heterogeneity from quantitative and classified high-throughput data. The radiomics approach has an analytic pipeline where the imaging features are extracted, processed and analyzed. At this point, special data handling is essential because it faces issues of a high-dimensional biomarker compared to a single biomarker approach. This article describes the potential role of radiomics in oncologic studies, the basic analytic pipeline and special data handling with high-dimensional data to facilitate the radiomics approach as a tool for personalized medicine in oncology.
http://ift.tt/2DWJ6uM
Non-small cell lung carcinoma with diffuse co-expression of thyroid transcription factor-1 and ΔNp63/p40
Here, we present a case of non-small cell lung carcinoma (NSCLC) with widespread and strong nuclear immunopositivity for both thyroid transcription factor-1 (TTF-1) and ΔNp63/p40 (p40). Double immunofluorescence for TTF-1 and p40 showed co-expression of both markers in the tumor cells. Furthermore, PTEN (pHis123Asp) and TP53 (pVal272Leu) mutations were identified as possible mitogenic driver mutations by next-generation sequencing. To the best of our knowledge, this is the first case of NSCLC harboring concurrent PTEN and TP53 mutations with widespread and strong coexpression of TTF-1 and p40, which has been confirmed in the resected specimen, and only the second documented case of NSCLC with TTF-1 and p40 diffuse coexpression in the carcinoma cells from the same individual.
http://ift.tt/2BNxBUX
Importance of frequency and morphological characteristics of nodular diabetic glomerulosclerosis in diabetic nephropathy
The Renal Pathology Society proposed a pathological classification for diabetic nephropathy (DN) (RPS 2010). We retrospectively examined the renal structural-functional relationships using the RPS 2010 classification in 49 DN cases. We also evaluated the importance of the percentage of glomeruli with nodular diabetic glomerulosclerosis and their morphological characteristics (cellular, cellular and extracellular matrix [ECM] or ECM types) in the pathology of DN. The classes of DN (RPS 2010) were significantly correlated with the duration of diabetes mellitus (DM), degree of proteinuria, a decreased estimated glomerular filtration rate (eGFR), and the stages of Japanese clinical DM and chronic kidney disease (CKD).
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Large inter-rater variability on EEG-reactivity is improved by a novel quantitative method
EEG-reactivity (EEG-R) has been defined as a change in EEG activity to stimulation (Hirsch et al., 2013). The most well-known type of EEG-R is the blocking of alpha activity to eye opening, which is most often present in healthy subjects. EEG-R is regarded as an important prognostic marker in comatose patients. In several studies, EEG-R predicts the comatose patient's awakening and recovery. This has been shown in patients with cardiac arrest (Wennervirta et al., 2009; Crepeau et al., 2013; Sandroni et al., 2013), after severe brain injury (Logi et al., 2011) and in ICU patients who are comatose due to anoxia, trauma, metabolic or infectious diseases (Young et al., 1999).
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IDEAL 2a phase-II study of ultra-focal brachytherapy for low and intermediate risk prostate cancer
Focal therapy of prostate cancer requires precise positioning of therapeutic agents within well-characterised index tumours (IT).We assessed the feasibility of low-dose-rate ultra-focal brachytherapy (UFB).
http://ift.tt/2ny8i3U
Bioluminescence Tomography Guided Small Animal Radiotherapy and Tumor Response Assessment
s: The image-guided SMall Animal Arc Radiation Treatment platform (iSMAART) has adopted onboard cone beam computed tomography (CBCT) and bioluminescence tomography (BLT). In this study, we used BLT to guide radiation delivery and quantitatively assess radiation-induced tumor response.
http://ift.tt/2DUG7r9
Electrocardiographic Changes in Hypothermia
A 76-year-old woman with a history of dementia and coronary heart disease was brought to the emergency department after she had been found lying outdoors for an undetermined period; her core body temperature was 26°C (78.8°F) at presentation. An electrocardiogram showed prominent Osborn waves, also…
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Urothelial Carcinoma
A 69-year-old woman presented to the emergency department with new-onset gross hematuria. Her medical history was notable for 20 pack-years of smoking. Results of a physical examination, complete blood count, and metabolic panel were normal. Urinalysis showed more than 100 red cells per high-power…
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Home Sweet Home
In this Journal feature, information about a real patient is presented in stages (boldface type) to an expert clinician, who responds to the information, sharing his or her reasoning with the reader (regular type). The authors' commentary follows. A 25-year-old woman presented to the emergency…
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Generation of superoxide and hydrogen peroxide by side reactions of mitochondrial 2-oxoacid dehydrogenase complexes in isolation and in cells
Journal Name: Biological Chemistry
Issue: Ahead of print
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Aβ42 oligomers impair the bioenergetic activity in hippocampal synaptosomes derived from APP-KO mice
Journal Name: Biological Chemistry
Issue: Ahead of print
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Screening for recommended antenatal risk factors: How long does it take?
Publication date: Available online 1 February 2018
Source:Women and Birth
Author(s): Amy Waller, Jamie Bryant, Emilie Cameron, Mohamed Galal, Ian Symonds, Rob Sanson-Fisher
BackgroundDetection and management of antenatal risk factors is critical for quality care.AimsTo determine (1) women's views about when they should be asked about antenatal health factors as recommended in the Australian antenatal guidelines; and (2) the time required to provide recommended care using a clinical scenario.MethodsIn Phase 1, pregnant women attending an outpatient obstetrics clinic at a public hospital were surveyed about preferred screening for antenatal risk factors during visit(s). In Phase 2, a hypothetical clinical scenario of a woman attending her first antenatal visit with a practicing midwife was video-recorded to extrapolate the time taken to ask about and offer assistance to manage clinical, screening and lifestyle risk factors.FindingsMost women (96%) perceived they should be asked about each of the risk factors at least once (i.e. at first visit). Total time taken to ask about all risk factors was 52min. More time was spent discussing clinical (11min) than lifestyle factors (4min). Adjusting for the estimated prevalence of each risk factor, the time taken to offer assistance was 8min per woman. Average time required for detecting and offering assistance to manage risk factors is 60min per average risk woman.ConclusionWomen are willing to be asked about risk factors; however this process is time-consuming. Strategies to streamline visits and prioritise recommendations so time-efficient yet comprehensive care can be delivered are needed, particularly when factors require monitoring over time and for those who may be 'at-risk' for multiple factors.
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Client experiences with perinatal healthcare for high-risk and low-risk women
Publication date: Available online 1 February 2018
Source:Women and Birth
Author(s): Cherelle M.V. van Stenus, Magda M. Boere-Boonekamp, Erna F.G.M. Kerkhof, Ariana Need
ProblemIt is unknown if client experiences with perinatal healthcare differ between low-risk and high-risk women.BackgroundIn the Netherlands, risk selection divides pregnant women into low- and high-risk groups. Receiving news that a pregnancy or childbirth has an increased likelihood of complications can cause elevated levels of emotional distress.AimThe purpose of this study is to describe client experiences with perinatal healthcare and to determine which, if any, background characteristics, pregnancy circumstances, childbirth or follow-up care characteristics are explaining variables of differences in client experiences between high-risk and low-risk women.MethodsClient experiences were measured with a validated questionnaire completed by 1388 women within 12 weeks after childbirth.FindingsWomen rated their experiences with perinatal healthcare with a mean score of 3.78 on a scale of 1–4; 5.5% of the women rated their experiences as "notably bad". Client experiences with perinatal healthcare show small variations, with a lower mean score for women who were at high risk (3.75) compared to low-risk women (3.84). This difference is partially due to more unplanned medical interventions and pain relief during childbirth in the high-risk group. Also, single mothers and non-Dutch women were more susceptible to less positive experiences.ConclusionGiven the potential negative impact of adverse client experiences, this study highlights the need for healthcare professionals to be aware of what women are susceptible for having had negative experiences. It is advised that healthcare provision be altered to tailor to the needs of these women.
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Sexual dysfunction predicts depressive symptoms during the first 2 years postpartum
Publication date: Available online 1 February 2018
Source:Women and Birth
Author(s): Shiow-Ru Chang, Wei-An Lin, Ho-Hsiung Lin, Ming-Kwang Shyu, Ming-I Lin
BackgroundThe association between sexual function and depression has yet to be examined in a prospective cohort study with prolonged postpartum follow-up.AimWe investigated whether sexual dysfunction predicted depressive symptoms during the 24-month postpartum period and examined the influence of obstetric factors.MethodsThis prospective 2-year cohort study with repeated measures included 196 participants who were recruited in a medical center in Taipei, Taiwan (2010–2011). Data on participants' personal characteristics, sexual function, and depression symptoms at 4–6 weeks and at 3, 6, 12, and 24 months postpartum were collected and then assessed using the Female Sexual Function Index and the Center for Epidemiologic Studies Depression Scale.ResultsAfter adjusting for time and covariates, women with sexual dysfunction had a 1.62-fold (95% confidence interval [CI]: 1.05–2.50-fold) higher estimated odds ratio (OR) for depressive symptoms during the entire 24 months after childbirth than did women without sexual dysfunction. Risk factors for depressive symptoms were a higher pain score (OR: 1.33, 95% CI: 1.13–1.57), a medical condition (OR: 1.65, 95% CI: 1.00–2.73), and severe perineal laceration (OR: 4.67, 95% CI: 1.37–15.92). Sexual satisfaction during the entire 24 months after childbirth (OR: 0.81, 95% CI: 0.70–0.95) and the highest personal income level (OR: 0.33, 95% CI: 0.11–0.99) were factors protecting against higher-scoring depressive symptoms.ConclusionsOur study provides robust evidence that sexual dysfunction and poor satisfaction, together with severe perineal laceration, greater pain, and a medical condition, predict depressive symptoms during the 24-month postpartum period.
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Antileukemic effects of neurokinin-1 receptor inhibition on hematologic malignant cells: a novel therapeutic potential for aprepitant
Genetic and laboratory studies have remodeled the conventional understanding of cancer pathogenesis by identifying different molecular alterations. Intrigued by the contribution of neurokinin-1 receptor (NK1R) network in cancer pathogenesis, we investigated the antileukemic effects of aprepitant, a nonpeptide antagonist of NK1R, in a panel of hematological cell lines. In this study, we found that aprepitant decreased the survival of all the tested cells; however, as compared with NB4, viability of the other cell lines was inhibited at higher concentrations. By increasing both p21 and p73 along with suppressing c-Myc and hTERT, aprepitant probably disordered cell distribution in the cell cycle, decreased DNA replication rate, and, thereby, impeded the proliferative capability of NB4 cells. Moreover, exposing cells to this agent led to activation of the caspase-3-dependent apoptotic pathway through altering the expression of apoptosis-related genes. Noteworthy, aprepitant also sensitized NB4 cells to the cytotoxic effects of arsenic trioxide and vincristine. Overall, it seems that pharmaceutical targeting of NK1R using aprepitant, either as a single agent or in combination, possesses novel promising potential for leukemia treatment strategies. Correspondence to Davood Bashash, PhD, Department of Hematology and Blood Banking, School of Allied Medical Sciences, Shahid Beheshti University of Medical Sciences, Tehran 1971653312, Iran Tel: +98 212 271 7504; fax: +98 212 272 1150; e-mail: d.bashash@sbmu.ac.ir Received July 18, 2017 Accepted December 12, 2017 Copyright © 2018 Wolters Kluwer Health, Inc. All rights reserved.
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Norleual, a hepatocyte growth factor and macrophage stimulating protein dual antagonist, increases pancreatic cancer sensitivity to gemcitabine
Pancreatic cancer is a leading cause of cancer deaths in the USA and is characterized by an exceptionally poor long-term survival rate compared with other major cancers. The hepatocyte growth factor (HGF) and macrophage stimulating protein (MSP) growth factor systems are frequently over-activated in pancreatic cancer and significantly contribute to cancer progression, metastasis, and chemotherapeutic resistance. Small molecules homologous to the 'hinge' region of HGF, which participates in its dimerization and activation, had been developed and shown to bind HGF with high affinity, antagonize HGF's actions, and possess anticancer activity. Encouraged by sequence homology between HGF's hinge region and a similar sequence in MSP, our laboratory previously investigated and determined that these same antagonists could also block MSP-dependent cellular responses. Thus, the purpose of this study was to establish that the dual HGF/MSP antagonist Norleual could inhibit the prosurvival activity imparted by both HGF and MSP to pancreatic cancer cells in vitro, and to determine whether this effect translated into an improved chemotherapeutic impact for gemcitabine when delivered in combination in a human pancreatic cancer xenograft model. Our results demonstrate that Norleual does indeed suppress HGF's and MSP's prosurvival effects as well as sensitizing pancreatic cancer cells to gemcitabine in vitro. Most importantly, treatment with Norleual in combination with gemcitabine markedly inhibited in-vivo tumor growth beyond the suppression observed with gemcitabine alone. These results suggest that dual functional HGF/MSP antagonists like Norleual warrant further development and may offer an improved therapeutic outcome for pancreatic cancer patients. Correspondence to Joseph W. Harding, PhD, Department of Integrative Physiology and Neuroscience, Washington State University, Pullman, WA 99164-6520, USA Tel: +1 509 335 7927; fax: +1 509 335 4650; e-mail: hardingj@vetmed.wsu.edu Received April 28, 2017 Accepted January 7, 2018 Copyright © 2018 Wolters Kluwer Health, Inc. All rights reserved.
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http://ift.tt/2FDHh6r
Dioscin inhibits colon cancer cells’ growth by reactive oxygen species-mediated mitochondrial dysfunction and p38 and JNK pathways
Dioscin is a natural steroid saponin derived from several plants that shows potent anticancer effects against a variety of cancer cells. Here, we investigated the antitumor effect of dioscin against human colon cancer cells and evaluated the molecular mechanism involved in this process. The cell cytotoxicity was studied by the MTT assay and BrdU incorporation. The proapoptotic mechanism of dioscin was characterized by flow cytometry analysis. A western blot and an immunofluorescence staining were used to investigate how dioscin induces apoptosis in vitro. In our study, dioscin could significantly inhibit the growth of colon cancer cells in a time-dependent and dose-dependent manner. Dioscin induces apoptosis and reactive oxygen species (ROS) generation, promoting the disruption of mitochondrial membrane potential, Bax translocation to the mitochondria, cytochrome C release to cytosol, activations of caspase-9/3, PARP cleavage, and subsequent apoptosis. Dioscin-induced apoptosis was accompanied by sustained phosphorylation of JNK, p38-MAPK. N-acetyl-L-cysteine, a scavenger of ROS, significantly reversed dioscin-induced cell death and activation of JNK and p38. Collectively, the data indicate that the induction of apoptosis by dioscin is mediated through ROS proteins, which are critical upstream signals for JNK/p38-MAPK activation. *Shu Li and Binbin Cheng contributed equally to the writing of this article. Correspondence to Shuang Li, MSc, Department of Gastroenterology, Baoshan Branch, Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai 201900, China Tel:+86 215 660 1100 x317 fax: +86 218 187 1559; e-mail: lishuangbs@126.com Received August 28, 2017 Accepted December 9, 2017 Copyright © 2018 Wolters Kluwer Health, Inc. All rights reserved.
http://ift.tt/2E4rOzr
http://ift.tt/2E4rOzr
Essential Metal Uptake in Gram-negative Bacteria: X-ray Fluorescence, Radioisotopes, and Cell Fractionation
A protocol for the extraction of a periplasmic transition metal chaperone in the context of its native binding partners, and biophysical characterization of its substrate contents by X-ray fluorescence and radiometal uptake is presented.
http://ift.tt/2EwghGF
The Most Powerful Sound You Will Never Hear
In a recent NPR Bio-Tech Nation interview, Focused Ultrasound Foundation Chairman Neal Kassell, MD, describes the theory and potential applications of this emerging approach to medical treatment. The treatment uses "multiple intersecting beams of high-frequency sound" to accurately target specific structures within the body with little effects on surrounding structures. Think magnifying glass and sunlight transformed into a concentrated and powerful beam of light.
http://ift.tt/2Evupjy
Ocaliva (obeticholic acid): Drug Safety Communication - Boxed Warning Added To Highlight Correct Dosing
Audience: Pharmacy, Hepatology, Gastroenterology [Posted 02/01/2018] ISSUE: FDA is warning that the liver disease medicine Ocaliva (obeticholic acid) has been incorrectly dosed daily instead of weekly in patients with moderate to severe primary...
http://ift.tt/2GAjc1Q
Ocaliva (obeticholic acid): Drug Safety Communication - Boxed Warning Added To Highlight Correct Dosing
Audience: Pharmacy, Hepatology, Gastroenterology [Posted 02/01/2018] ISSUE: FDA is warning that the liver disease medicine Ocaliva (obeticholic acid) has been incorrectly dosed daily instead of weekly in patients with moderate to severe primary...
http://ift.tt/2GAjc1Q
Paradigms of Lower Extremity Electrical Stimulation Training After Spinal Cord Injury
Spinal cord injury is a traumatic medical condition that may result in elevated risks of chronic secondary metabolic disorders. Here, we presented a protocol using surface neuromuscular electrical stimulation-resistance training in conjunction with functional electrical stimulation-lower extremities cycling as a strategy to ameliorate several of these medical problems.
http://ift.tt/2BMMNkU
Diffusion Tensor Imaging of Dystrophic Skeletal Muscle
Abstract
Purpose
To compare the influence of two different regions of interest (ROIs) on diffusion tensor metrics in dystrophic thigh muscles using a custom-made (whole muscle) ROI including and a selective ROI excluding areas of fatty replacement.
Methods
Diffusion tensor imaging (DTI) and chemical-shift-encoded water-fat magnetic resonance imaging (MRI) of the thigh was conducted on a 3-Tesla system in 15 cases with muscular dystrophy and controls. The ROIs were chosen according to patterns of fatty replacement on co-registered axial DTI and gradient echo sequence (GRE) images. Fractional anisotropy (FA), apparent diffusion coefficient (ADC), fiber track length (FTL), and muscle fat fractions (MFF) were compared between both ROI segmentations. These comparisons, muscle-specific correlation coefficients, and the influence of ROI localization on tensor metrics were derived based on linear mixed effects regression models.
Results
In the cases a high correlation was observed for ADC and FA with MFF using a custom ROI. The correlation was weaker but still significant with a selective ROI method. Using the custom ROI, FTL correlated significantly with MFF in 3 out of 4 muscles (r ≤ −0.51). A correlation was not found for the selective ROI method. Interaction analysis revealed that the association of ADC and FA with MFF was not significantly influenced by the ROI localization. For FTL the ROI localization significantly reduced the negative association with MFF.
Conclusion
The DTI metrics and FTL of custom ROI segmentation are significantly influenced by MFF. Contrary to ADC and FA, the effect of MFF on FTL is significantly reduced when applying selective ROI segmentation, which could therefore be a better option for MR tractography.
http://ift.tt/2FBLPdI
Community structure explains antibiotic resistance gene dynamics over a temperature gradient in soil
Abstract
Soils are reservoirs of antibiotic resistance genes (ARGs), but environmental dynamics of ARGs are largely unknown. Long-term disturbances offer opportunities to examine microbiome responses at scales relevant for both ecological and evolutionary processes and can be insightful for studying ARGs. We examined ARGs in soils overlying the underground coal seam fire in Centralia, PA, which has been burning since 1962. As the fire progresses, previously hot soils can recover to ambient temperatures, which creates a gradient of fire impact. We examined metagenomes from surface soils along this gradient to examine ARGs using a gene-targeted assembler. We targeted 35 clinically-relevant ARGs and two horizontal gene transfer-related genes (intI and repA). We detected 17 ARGs in Centralia: AAC6-Ia, adeB, bla_A, bla_B, bla_C, cmlA, dfra12, intI, sul2, tetA, tetW, tetX, tolC, vanA, vanH, vanX, and vanZ. The diversity and abundance of bla_A, bla_B, dfra12, and tolC decreased with soil temperature, and changes in ARGs were largely explained by changes in community structure. We observed sequence-specific biogeography along the temperature gradient and observed compositional shifts in bla_A, dfra12, and intI. These results suggest that increased temperatures can reduce soil ARGs but that this is largely due to a concomitant reduction in community-level diversity.http://ift.tt/2E6fbnf
Genomic insights into metabolic potentials of two simultaneous aerobic denitrification and phosphorus removal bacteria Achromobacter sp. GAD3 and Agrobacterium sp. LAD9
Abstract
Bacteria capable of simultaneous aerobic denitrification and phosphorus removal (SADPR) are promising to establish novel one-stage wastewater treatment systems. Nevertheless, insights into metabolic potentials of SADPR related bacteria are limited. Here, comprehensive metabolic models of two efficient SADPR bacteria Achromobacter sp. GAD3 and Agrobacterium sp. LAD9 were yielded for the first time by high-throughput genome sequencing. With succinate as the preferred carbon source, both strains employed a complete TCA cycle as the major carbon metabolism for various organic acids and complex carbon oxidation potentials. Complete and truncated aerobic denitrification routes were confirmed in GAD3 and LAD9, respectively, facilitated by all major components of electron transfer chain via oxidative phosphorylation. Comparative genome analysis revealed distinctive ecological niches involved in denitrifying potential among different phylogenetic clades within Achromobacter and Agrobacterium. Excellent phosphorus removal capacities were contributed by inorganic phosphate uptake, polyphosphate synthesis and phosphonate metabolism. Additionally, the physiology of GAD3/LAD9 is different to that displayed by most available polyphosphate accumulating organisms (PAOs), and reveals both strains to be more versatile, carrying out diverse organics degradation potentials and outstanding SADPR capacity within a single organism. The functional explorations of SADPR bacteria broaden their significant application prospects in concurrent carbon and nutrients removal aerobically.http://ift.tt/2FDyW2X
Adapting the Elixhauser comorbidity index for cancer patients
BACKGROUND
This study was designed to adapt the Elixhauser comorbidity index for 4 cancer-specific populations (breast, prostate, lung, and colorectal) and compare 3 versions of the Elixhauser comorbidity score (individual comorbidities, summary comorbidity score, and cancer-specific summary comorbidity score) with 3 versions of the Charlson comorbidity score for predicting 2-year survival with 4 types of cancer.
METHODS
This cohort study used Texas Cancer Registry–linked Medicare data from 2005 to 2011 for older patients diagnosed with breast (n = 19,082), prostate (n = 23,044), lung (n = 26,047), or colorectal cancer (n = 16,693). For each cancer cohort, the data were split into training and validation cohorts. In the training cohort, competing risk regression was used to model the association of Elixhauser comorbidities with 2-year noncancer mortality, and cancer-specific weights were derived for each comorbidity. In the validation cohort, competing risk regression was used to compare 3 versions of the Elixhauser comorbidity score with 3 versions of the Charlson comorbidity score. Model performance was evaluated with c statistics.
RESULTS
The 2-year noncancer mortality rates were 14.5% (lung cancer), 11.5% (colorectal cancer), 5.7% (breast cancer), and 4.1% (prostate cancer). Cancer-specific Elixhauser comorbidity scores (c = 0.773 for breast cancer, c = 0.772 for prostate cancer, c = 0.579 for lung cancer, and c = 0.680 for colorectal cancer) performed slightly better than cancer-specific Charlson comorbidity scores (ie, the National Cancer Institute combined index; c = 0.762 for breast cancer, c = 0.767 for prostate cancer, c = 0.578 for lung cancer, and c = 0.674 for colorectal cancer). Individual Elixhauser comorbidities performed best (c = 0.779 for breast cancer, c = 0.783 for prostate cancer, c = 0.587 for lung cancer, and c = 0.687 for colorectal cancer).
CONCLUSIONS
The cancer-specific Elixhauser comorbidity score performed as well as or slightly better than the cancer-specific Charlson comorbidity score in predicting 2-year survival. If the sample size permits, using individual Elixhauser comorbidities may be the best way to control for confounding in cancer outcomes research. Cancer 2018. © 2018 American Cancer Society.
http://ift.tt/2BLIVRq
Satisfaction with cancer care, self-efficacy, and health-related quality of life in Latino cancer survivors
BACKGROUND
The objective of the current study was to examine how modifiable factors such as satisfaction with cancer care and self-efficacy impact health-related quality of life (HRQOL) among Latino cancer survivors.
METHODS
Latinos previously diagnosed with breast, prostate, or colorectal cancer (N = 288) completed questionnaires (Patient Satisfaction with Cancer Care Scale, Stanford Chronic Disease Self-Management Measures, Functional Assessment of Cancer Therapy-General, and Short Acculturation Scale for Hispanics) within 2 years after receiving primary cancer treatment.
RESULTS
Path model analyses demonstrated that satisfaction with cancer care was associated with greater HRQOL and that this relationship was explained by several facets of self-efficacy (ie, confidence in managing psychological distress [z = 3.81; P<.001], social support from close others [z = 2.46; P = .014], social/recreational activities [z = 3.30; P = .001], and patient-provider communication [z = −3.72; P<.001]). Importantly, foreign-born, less acculturated, and monolingual Spanish-speaking survivors reported lower self-efficacy in patient-provider communication; however, adjusting for acculturation, language, nativity, and other covariates did not alter these results.
CONCLUSIONS
Factors that contribute to disparities in HRQOL among Latino cancer survivors compared with non-Latino whites, such as low income, less education, and a lack of health insurance, can be difficult to address. The findings of the current study emphasize the importance of self-efficacy within the context of patient-centered cancer care practices (eg, patient inclusion in care decisions, sufficient time with provider, ready access to medical advice) and suggest that improving satisfaction with care may increase patients' confidence in managing important aspects of their cancer experience and, in turn, improve HRQOL among Latino cancer survivors. Cancer 2018. © 2018 American Cancer Society.
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Primordial Germ Cell Transplantation for CRISPR/Cas9-based Leapfrogging in Xenopus
http://ift.tt/2DRonbP
The Use of a β-lactamase-based Conductimetric Biosensor Assay to Detect Biomolecular Interactions
In this work, we report a new method to study protein-protein interactions using a conductimetric biosensor based on the hybrid β-lactamase technology. This method relies on release of protons upon hydrolysis of β-lactams.
http://ift.tt/2EwRDpE
Complement factor H protects mice from ischemic acute kidney injury but is not critical for controlling complement activation by glomerular IgM
Abstract
Natural IgM binds to glomerular epitopes in several progressive kidney diseases. Previous work has shown that IgM also binds within the glomerulus after ischemia/reperfusion (I/R) but does not fully activate the complement system. Factor H is a circulating complement regulatory protein, and congenital or acquired deficiency of factor H is a strong risk factor for several types of kidney disease. We hypothesized that factor H controls complement activation by IgM in the kidney after I/R, and that heterozygous factor H deficiency would permit IgM-mediated complement activation and injury at this location. We found that mice with targeted heterozygous deletion of the gene for factor H developed more severe kidney injury after I/R than wild-type controls, as expected, but that complement activation within the glomeruli remained well controlled. Furthermore, mice that are unable to generate soluble IgM were not protected from renal I/R, even in the setting of heterozygous factor H deficiency. These results demonstrate that factor H is important for limiting injury in the kidney after I/R, but it is not critical for controlling complement activation by immunoglobulin within the glomerulus in this setting. IgM binds to glomerular epitopes after I/R, but it is not a significant source of injury.
This article is protected by copyright. All rights reserved
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Diabetes: Look after your teeth to look after your blood glucose
Good oral health can benefit people with type 2 diabetes by significantly improving their blood glucose levels, a new study suggests.
http://ift.tt/2EwHNEe
Importance of complete phenotyping in prenatal whole exome sequencing
Abstract
Whole exome sequencing (WES) is an emerging technique in prenatal diagnosis. In this retrospective study, we examined diagnostic utility and limitations of WES in prenatal cases with structural birth defects. DNA from 20 trios (fetal and parental), with normal karyotype and microarray findings, underwent WES and variant interpretation at a reference laboratory. The WES results were later re-evaluated in our academic center utilizing prenatal and postnatal phenotyping. Initial analysis using only prenatal ultrasound findings revealed no pathogenic or likely pathogenic variants in 20 pregnancies with structural birth defects. Re-analysis of WES variants and combination of prenatal and postnatal phenotyping yielded pathogenic variants in at least 20% of cases including PORCN gene in a fetus with split-hand/foot malformation, as well as variants of uncertain significance in NEB and NOTCH1 in fetuses with postnatal muscle weakness and Adams–Oliver syndrome, respectively. Furthermore, Sanger sequencing in a patient with holoprosencephaly, elucidated by postnatal MRI, revealed a pathogenic 47-base pairs deletion in ZIC2 which was missed by prenatal WES. This study suggests that incomplete prenatal phenotyping and lack of prenatal ultrasound-genotype databases are the limiting factors for current interpretation of WES data in prenatal diagnosis. Development of prenatal phenotype–genotype databases would significantly help WES interpretation in this setting. Patients who underwent prenatal clinical WES may benefit from the re-analysis based on detailed postnatal findings.
http://ift.tt/2nsRCvF
Tracing Stem Cell Division in Adult Neurogenesis
Neural stem cells in the ventricular-subventricular zone of the adult brain continuously generate differentiated neurons without depleting the stem cell pool. In this issue of Cell Stem Cell, Obernier et al. (2018) present the surprising finding that this occurs through mostly symmetric divisions that either generate two differentiating or two self-renewing daughter cells.
http://ift.tt/2rXPn8l
Meddling with METTLs in Normal and Leukemia Stem Cells
Three recent studies independently identified the m6A RNA modifying enzymes METTL3 and METTL14 as critical regulators of differentiation in both normal hematopoiesis and AML pathogenesis. These studies expand the described roles of the epitranscriptome in maintaining the undifferentiated state in somatic stem cells and human cancer.
http://ift.tt/2GCc4lF
Jak1 Integrates Cytokine Sensing to Regulate Hematopoietic Stem Cell Function and Stress Hematopoiesis
(Cell Stem Cell 21, 489–501; October 5, 2017)
http://ift.tt/2rXPelj
In Vivo Labeling by CD73 Marks Multipotent Stromal Cells and Highlights Endothelial Heterogeneity in the Bone Marrow Niche
Breitbach et al. generated a CD73-EGFP reporter mouse that enabled identification and tracking of multipotent stromal cells in vivo. CD73-EGFP also labeled sinusoidal endothelial cells within the bone marrow, enabling the molecular characterization of this important endothelial component of the hematopoietic stem cell niche.
http://ift.tt/2GDZToc
Japan Strengthens Regenerative Medicine Oversight
The Japanese government initiated sweeping reforms targeting regenerative medicine in 2014, accompanied by substantial investment into stem cell research and development. We survey the impact of these developments and discuss how the government is working to accelerate regenerative medicine while ensuring safety and efficacy.
http://ift.tt/2rXP6SR
Shaping the Pluripotent Genome: Switches, Borders, and Loops
Three-dimensional genome organization is largely cell type specific and requires reorganization during cell fate transitions. A recent study in Nature Genetics (Stadhouders et al., 2018) offers important insights into the principles and drivers of such reorganization during reprogramming of somatic cells into pluripotent stem cells.
http://ift.tt/2GBUxKt
Adult Neurogenesis Is Sustained by Symmetric Self-Renewal and Differentiation
Obernier et al. show that juvenile/adult neural stem cells (NSCs) generate progeny or self-renew through symmetric divisions. The prevailing consuming symmetric divisions progressively deplete NSCs, yet this mechanism enables lifelong generation of large numbers of neurons for the olfactory bulb while decoupling proliferation from differentiation.
http://ift.tt/2rTJk4k
Slow Your Roll: Inhibiting SETD7 Activity Permits Ex Vivo Expansion of Muscle Stem Cells
Muscle stem cell regenerative capacity is rapidly lost during ex vivo culture. In this issue of Cell Stem Cell, Judson et al. (2018) show that inhibition of cytoplasmic SETD7, a lysine methyltransferase, potently expands naive, undifferentiated mouse and human muscle stem cells by restricting their progression through the myogenic program.
http://ift.tt/2GCdaxH
Mentoring the Next Generation: Irving Weissman
Mentor-mentee relationships are essential for professional development, but developing these interpersonal skills is not often highlighted as a priority in scientific endeavors. In a yearlong series, Cell Stem Cell interviews prominent scientists who have prioritized mentorship over the years. Here, we chat with Dr. Irving Weissman about his views.
http://ift.tt/2rZ7jiS
Clonal Hematopoiesis and Evolution to Hematopoietic Malignancies
Bowman et al. discuss the clinical manifestations of clonal hematopoiesis (CH), mechanisms contributing to its development, the role of CH in clonal evolution towards leukemia, and the contribution of CH to non-hematological disease states.
http://ift.tt/2GEmhOu
FAOund the Link: Phospholipid Remodeling and Intestinal Stem Cell Growth and Tumorigenesis
In this issue of Cell Stem Cell, Wang et al. (2018) identify a novel link between Lpcat3-mediated phospholipid remodeling (the Lands cycle) and cholesterol biosynthesis that modulates intestinal stem cell proliferation and tumorigenesis. Notably, inhibition of cholesterol biosynthesis dampens many of the Lpcat3-deficiency-mediated effects in the intestine.
http://ift.tt/2rX4ejb
Association of urinary and plasma DNA in early breast cancer patients and its links to disease relapse
Abstract
Purpose
Identifying patients who are at risk of relapse is a key challenge of primary breast cancer. The current study investigates the utility of urinary DNA in breast cancer management and as a predictor of relapse. This work also compares the sensitivity of plasma DNA with urinary DNA.
Methods
Blood plasma and urine specimens were collected concurrently from 200 breast cancer patients receiving neoadjuvant chemotherapy. Comparison of both plasma and urinary DNA was performed at baseline to determine assay significance. Serial measurements of urinary DNA were conducted to gauge DNA variations after surgery. Correlations to disease relapse were performed to affirm the clinical utility of urinary DNA.
Results
Molecular analysis showed patients were successfully identified with mutant PIK3CA using urinary DNA. A strong correlation was affirmed from urinary and plasma DNA at baseline with the correlation coefficient r = 0.859. We analyzed post-surgery measurements of urinary DNA for disease-relapse predictions. In subsequent serial followup of urinary DNA samples, we confirmed increased sensitivity in predicting relapse of these patients. The hazard ratio determined at the 9-month was 1.51 that identified patients at greater risk of disease relapse.
Conclusion
Urinary DNA offers a unique opportunity to glimpse upon dynamic changes in early breast cancer. Our results demonstrated good correlation to plasma DNA and post monitoring of cancer patients to identify individuals susceptible to a high risk of relapse. This potentially allows for early intervention such as adjuvant chemotherapy to be administered to better manage these patients.
http://ift.tt/2GEm9yu
Detecting Anastasis In Vivo by CaspaseTracker Biosensor
http://ift.tt/2FAyCSn
Incidence of diabetes mellitus-related comorbidities among patients attending two major HIV clinics in Botswana: a 12-year retrospective cohort study
Exposure to combination antiretroviral therapy (cART) is associated with the development of diabetes mellitus related comorbidities (DRCs). This study aims to: (i) estimate the incidence of DRCs among cART rec...
http://ift.tt/2nwxess
Maternal and neonatal characteristics that influence very early neonatal mortality in the Eastern Regional Hospital of Ghana, Koforidua: a retrospective review
This study was conducted to determine the maternal and neonatal characteristics that influence very early neonatal mortality using 811 delivery records at the Eastern Regional Hospital of Ghana.
http://ift.tt/2DUIXw4
Automated cell cycle and cell size measurements for single-cell gene expression studies
Recent rise of single-cell studies revealed the importance of understanding the role of cell-to-cell variability, especially at the transcriptomic level. One of the numerous sources of cell-to-cell variation i...
http://ift.tt/2nx0pMc
The Challenging Quest to Improve Rural Health Care
Major rural health issues — a chronic shortage of doctors, dentists, pharmacists, and nonphysician providers; a wave of hospital closures; and a widening gap in life expectancy that favors the urban populace over rural residents — continue to test the fragile system of rural care in the United…
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The “Obesity Paradox” in Chronic Obstructive Pulmonary Disease: Can It Be Resolved?
http://ift.tt/2BLqWKC
Treatment Setting and Outcomes of Cystic Fibrosis Pulmonary Exacerbations
Annals of the American Thoracic Society, Volume 15, Issue 2, Page 225-233, February 2018.
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Obesity and Severity of Acute Exacerbation of Chronic Obstructive Pulmonary Disease
Annals of the American Thoracic Society, Volume 15, Issue 2, Page 184-191, February 2018.
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Reply: We Did This, and the Patient Improved: True, True, and Unrelated?
Annals of the American Thoracic Society, Volume 15, Issue 2, Page 269-269, February 2018.
http://ift.tt/2BLqSdQ
Treating Cystic Fibrosis Pulmonary Exacerbations: In the Hospital with a Physician or at Home under Your Own Supervision?
http://ift.tt/2BLrJv5
Dietary Influences on Asthma: The Generational Impact of a Sweet Tooth?
http://ift.tt/2nsoRit
The Effect of Defining Chronic Obstructive Pulmonary Disease by the Lower Limit of Normal of FEV1/FVC Ratio in Tiotropium Safety and Performance in Respimat Participants
Annals of the American Thoracic Society, Volume 15, Issue 2, Page 200-208, February 2018.
http://ift.tt/2BKGTAX
We Did This, and the Patient Improved: True, True, and Unrelated?
Annals of the American Thoracic Society, Volume 15, Issue 2, Page 268-268, February 2018.
http://ift.tt/2BJhDLw
Bilateral Indwelling Pleural Catheters for Pleural Effusions Secondary to Nonmalignant Superior Vena Cava Obstruction
http://ift.tt/2ntkZhs
Rationale and Design of an Adaptive Phase 2b/3 Clinical Trial of Selepressin for Adults in Septic Shock. Selepressin Evaluation Programme for Sepsis-induced Shock—Adaptive Clinical Trial
Annals of the American Thoracic Society, Volume 15, Issue 2, Page 250-257, February 2018.
http://ift.tt/2nslxE4
Socioeconomic differences in hearing among middle-aged and older adults: cross-sectional analyses using the Health Survey for England
Background
Hearing loss impacts on cognitive, social and physical functioning. Both hearing loss and hearing aid use vary across population subgroups. We examined whether hearing loss, and reported current hearing aid use among persons with hearing loss, were associated with different markers of socioeconomic status (SES) in a nationally representative sample of community-dwelling middle-aged and older adults.
MethodsHearing was measured using an audiometric screening device in the Health Survey for England 2014 (3292 participants aged 45 years and over). Hearing loss was defined as >35 dB HL at 3.0 kHz in the better-hearing ear. Using sex-specific logistic regression modelling, we evaluated the associations between SES and hearing after adjustment for potential confounders.
Results26% of men and 20% of women aged 45 years and over had hearing loss. Hearing loss was higher among men in the lowest SES groups. For example, the multivariable-adjusted odds of hearing loss were almost two times as high for those in the lowest versus the highest income tertile (OR 1.77, 95% CI 1.15 to 2.74). Among those with hearing loss, 30% of men and 27% of women were currently using a hearing aid. Compared with men in the highest income tertile, the multivariable-adjusted odds of using a hearing aid nowadays were lower for men in the middle (OR 0.50, 95% CI 0.25 to 0.99) and the lowest (OR 0.47, 95% CI 0.23 to 0.97) income tertiles. Associations between SES and hearing were weaker or null among women.
ConclusionsWhile the burden of hearing loss fell highest among men in the lowest SES groups, current hearing aid use was demonstrably lower. Initiatives to detect hearing loss early and increase the uptake and the use of hearing aids may provide substantial public health benefits and reduce socioeconomic inequalities in health.
http://ift.tt/2DQdOG5
Training approaches for the deployment of a mechanical chest compression device: a randomised controlled manikin study
Objectives
To evaluate the effect of training strategy on team deployment of a mechanical chest compression device.
DesignRandomised controlled manikin trial.
SettingLarge teaching hospital in the UK.
ParticipantsTwenty teams, each comprising three clinicians. Participating individuals were health professionals with intermediate or advanced resuscitation training.
InterventionsTeams were randomised in a 1:1 ratio to receive either standard mechanical chest compression device training or pit-crew device training. Training interventions lasted up to 1 h. Performance was measured immediately after training in a standardised simulated cardiac arrest scenario in which teams were required to deploy a mechanical chest compression device.
Primary and secondary outcome measuresPrimary outcome was chest compression flow fraction in the minute preceding the first mechanical chest compression. Secondary outcomes included cardiopulmonary resuscitation quality and mechanical device deployment metrics, and non-technical skill performance. Outcomes were assessed using video recordings of the test scenario.
ResultsIn relation to the primary outcome of chest compression flow fraction in the minute preceding the first mechanical chest compression, we found that pit-crew training was not superior to standard training (0.76 (95% CI 0.73 to 0.79) vs 0.77 (95% CI 0.73 to 0.82), mean difference –0.01 (95% CI –0.06 to 0.03), P=0.572). There was also no difference between groups in performance in relation to any secondary outcome.
ConclusionsPit-crew training, compared with standard training, did not improve team deployment of a mechanical chest device in a simulated cardiac arrest scenario.
Trial registration numberISRCTN43049287; Pre-results.
http://ift.tt/2Euhnmj
Prevalence of tobacco consumption among young physicians at a regional university hospital in southern Spain: a cross-sectional study
Introduction
The aim of the study is to analyse the prevalence of smoking among resident physicians at a regional university hospital. In addition, we examined the trends in the smoking behaviour of physicians in relation to results obtained in other studies carried out previously at this hospital, as well as those published nationally and internationally
MethodA cross-sectional observational study evaluating tobacco consumption in young physicians was carried out at the level of secondary healthcare in a regional university hospital in Cordoba, Spain. All the study subjects were resident physicians who underwent a mandatory preliminary occupational health examination between 2012 and 2016. There was no sampling selection as anyone who took this examination was considered to be within the target population. We calculated the proportions of smokers, former smokers and non-smokers, with 95% CIs. Univariate and multivariate analyses (binary logistic regression) were used to analyse the results (P<0.05).
ResultsThe response rate was 99.4%, with a sample size of 324 out of a possible 326 physicians. The average age was 28.6±3.7—DT—(95% CI 28.2 to 29.0), and 62.3% (202/324; 95% CI 57.3 to 67.2) were women. Smoking prevalence was 6.5% (21/324; 95% CI 3.5 to 9.3) with a further 5.2% (17/324; 95% CI 2.7 to 7.8) being ex-smokers. There were no significant differences in the prevalence of tobacco consumption according to age (P=0.266), sex (9.0% for men and 5.0% for women; P=0.128), medical specialty (P=0.651) or year of residency (P=0.975). A 52.7% decline in the number of young physician smokers was noted between 1986 and 2016 (95% CI –44.0 to –63.5), together with a 64.4% increase in non-smokers (95% CI 55.2 to 77.3).
ConclusionsWe observed a significantly low prevalence of tobacco use among trainee physicians in the cohort, an effect of new antismoking laws, with positive role model implications for new physicians and medical students.
http://ift.tt/2DTj63C
The cost of mental and physical health disability in childhood and adolescence to families in the UK: findings from a repeated cross-sectional survey using propensity score matching
Objective
In the UK, families of disabled children are entitled to receive disability benefits to help meet costs associated with caring for their child. Evidence of actual costs incurred is scant, especially for mental health disability. In this study, we aimed to quantify the cost of mental and physical health disability in childhood and adolescence to families in the UK using the concept of compensating variation (CV).
DesignRepeated cross-sectional survey.
SettingThe UK general population
Participants85 212 children drawn from 8 waves of the Family Resources Survey.
OutcomesUsing propensity score matching we matched families with a disabled child to similar families without a disabled child and calculated the extra income the former require to achieve the same living standards as the latter, that is, their CV. We calculated the additional costs specifically associated with several definitions of mental health and physical health disability.
ResultsFamilies of a child with any mental health disability, regardless of the presence of physical health comorbidity, needed an additional £49.31 (95% CI: 21.95 to 76.67) and, for more severe disabilities, an additional £57.56 (95% CI: 17.69 to 97.44) per week to achieve the same living standards of families without a disabled child. This difference was greater for more deprived families, who needed between £59.28 (95% CI: 41.38 to 77.18) and £81.26 (95% CI: 53.35 to 109.38) more per week depending on the extent of mental health disability. Families of children with physical health disabilities, with or without mental health disabilities, required an additional £35.86 (95% CI: 13.77 to 57.96) per week, with economically deprived families requiring an extra £42.18 (95% CI: 26.38 to 57.97) per week.
ConclusionsMental and physical health disabilities among children and adolescents were associated with high additional costs for the family, especially for those from deprived economic backgrounds. Means testing could help achieve a more equitable redistribution of disability benefit.
http://ift.tt/2DSqhcr
Feasibility study to assess the impact of a lifestyle intervention ('LivingWELL) in people having an assessment of their family history of colorectal or breast cancer
Objectives
To assess the feasibility of delivering and evaluating a weight management (WM) programme for overweight patients with a family history (FH) of breast cancer (BC) or colorectal cancer (CRC).
Study designA two-arm (intervention vs usual care) randomised controlled trial.
SettingNational Health Service (NHS) Tayside and NHS Grampian.
ParticipantsPeople with a FH of BC or CRC aged≥18 years and body mass index of ≥25 kg/m2 referred to NHS genetic services.
InterventionParticipants were randomised to a control (lifestyle booklet) or 12-week intervention arm where they were given one face-to-face counselling session, four telephone consultations and web-based support. A goal of 5% reduction in body weight was set, and a personalised diet and physical activity (PA) programme was provided. Behavioural change techniques (motivational interviewing, action and coping plans and implementation intentions) were used.
Primary outcomeFeasibility measures: recruitment, programme implementation, fidelity measures, achieved measurements and retention, participant satisfaction assessed by questionnaire and qualitative interviews.
Secondary outcomesMeasured changes in weight and PA and reported diet and psychosocial measures between baseline and 12-week follow-up.
ResultsOf 480 patients approached, 196 (41%) expressed interest in the study, and of those, 78 (40%) patients were randomised. Implementation of the programme was challenging within the time allotted and fidelity to the intervention modest (62%). Qualitative findings indicated the programme was well received. Questionnaires and anthropometric data were completed by >98%. Accelerometer data were attained by 84% and 54% at baseline and follow-up, respectively. Retention at 12 weeks was 76%. Overall, 36% of the intervention group (vs 0% in control) achieved 5% weight loss. Favourable increases in PA and reduction in dietary fat were also reported.
ConclusionsA lifestyle programme for people with a family history of cancer is feasible to conduct and acceptable to participants, and indicative results suggest favourable outcomes.
Trial registration numberhttp://ift.tt/2EvZjbx
Single-trial log transformation is optimal in frequency analysis of resting EEG alpha
Abstract
The appropriate definition and scaling of the magnitude of EEG oscillations is an underdeveloped area. The aim of this study was to optimize the analysis of resting EEG alpha magnitude, focusing on alpha peak frequency and non-linear transformation of alpha power. A family of non-linear transforms, Box-Cox transforms, were applied to find the transform that (a) maximized a non-disputed effect: the increase in alpha magnitude when the eyes are closed (Berger effect), and (b) made the distribution of alpha magnitude closest to normal across epochs-within each participant, or across participants. The transformations were done either at the single epoch level, or at the epoch-average level. Alpha peak frequency showed large individual differences, yet good correspondence between various ways to estimate it in two minutes of eyes-closed and two minutes of eyes-open resting EEG data. Both alpha magnitude and the Berger effect were larger for individual alpha than for a generic (8-12 Hz) alpha band. The log transform on single epochs (a) maximized the t-value of the contrast between the eyes-open and eyes-closed condition when tested within each participant, and (b) rendered near-normally distributed alpha power across epochs and participants, thereby making further transformation of epoch-averages superfluous. The results suggest that the log-normal distribution is a fundamental property of variations in alpha power across time in the order of seconds. Moreover, effects on alpha power appear to be multiplicative rather than additive. These findings support the use of the log transform on single epochs to achieve appropriate scaling of alpha magnitude.
This article is protected by copyright. All rights reserved.
http://ift.tt/2nu6t8W
ASK1 Inhibition Halts Disease Progression in Preclinical Models of Pulmonary Arterial Hypertension
American Journal of Respiratory and Critical Care Medicine, Volume 197, Issue 3, Page 373-385, February 1, 2018.
http://ift.tt/2rXc5x4
Therapeutic Value of ASK1 Inhibition in Pulmonary Arterial Hypertension
American Journal of Respiratory and Critical Care Medicine, Volume 197, Issue 3, Page 284-286, February 1, 2018.
http://ift.tt/2GCI9tz
Chronic Obstructive Pulmonary Disease Alters Immune Cell Composition and Immune Checkpoint Inhibitor Efficacy in Non–Small Cell Lung Cancer
American Journal of Respiratory and Critical Care Medicine, Volume 197, Issue 3, Page 325-336, February 1, 2018.
http://ift.tt/2s1uh93
Reply to Verbanck and Vanderhelst: The Respective Roles of Lung Clearance Index and Magnetic Resonance Imaging in the Clinical Management of Patients with Cystic Fibrosis
American Journal of Respiratory and Critical Care Medicine, Volume 197, Issue 3, Page 411-412, February 1, 2018.
http://ift.tt/2GDL2tV
Proteomic Profiles Associated with Early Echocardiogram Evidence of Pulmonary Vascular Disease in Preterm Infants
American Journal of Respiratory and Critical Care Medicine, Volume 197, Issue 3, Page 394-397, February 1, 2018.
http://ift.tt/2GBJ7pZ
Cardiovascular Disease Does Not Predict Exacerbation Rate or Mortality in Chronic Obstructive Pulmonary Disease
American Journal of Respiratory and Critical Care Medicine, Volume 197, Issue 3, Page 400-403, February 1, 2018.
http://ift.tt/2s1FOoE
Research Priorities in Pathophysiology for Sleep-disordered Breathing in Patients with Chronic Obstructive Pulmonary Disease. An Official American Thoracic Society Research Statement
American Journal of Respiratory and Critical Care Medicine, Volume 197, Issue 3, Page 289-299, February 1, 2018.
http://ift.tt/2Gzt4ca
Unilateral Acute Respiratory Distress Syndrome with Contralateral Pulmonary Artery Agenesis
American Journal of Respiratory and Critical Care Medicine, Volume 197, Issue 3, Page 386-387, February 1, 2018.
http://ift.tt/2GEYfTp
Nintedanib with Add-on Pirfenidone in Idiopathic Pulmonary Fibrosis. Results of the INJOURNEY Trial
American Journal of Respiratory and Critical Care Medicine, Volume 197, Issue 3, Page 356-363, February 1, 2018.
http://ift.tt/2rXozVL
What Is Sarcoidosis?
American Journal of Respiratory and Critical Care Medicine, Volume 197, Issue 3, Page P3-P3, February 1, 2018.
http://ift.tt/2GDvXZm
The Respective Roles of Lung Clearance Index and Magnetic Resonance Imaging in the Clinical Management of Patients with Cystic Fibrosis
American Journal of Respiratory and Critical Care Medicine, Volume 197, Issue 3, Page 409-409, February 1, 2018.
http://ift.tt/2rXVGbN
Reply to Fayssoil: Pulmonary Endpoints in Duchenne Muscular Dystrophy: Evaluation of the Structure and Function of Respiratory Muscles by Ultrasonography
American Journal of Respiratory and Critical Care Medicine, Volume 197, Issue 3, Page 405-405, February 1, 2018.
http://ift.tt/2GzsPOi
IFN-stimulated Gene Expression, Type 2 Inflammation, and Endoplasmic Reticulum Stress in Asthma
American Journal of Respiratory and Critical Care Medicine, Volume 197, Issue 3, Page 313-324, February 1, 2018.
http://ift.tt/2rUoK48
Effect of Early-Life Geohelminth Infections on the Development of Wheezing at 5 Years of Age
American Journal of Respiratory and Critical Care Medicine, Volume 197, Issue 3, Page 364-372, February 1, 2018.
http://ift.tt/2Gzsew2
A Twist on Pulmonary Vascular Remodeling: Endothelial to Mesenchymal Transition?
American Journal of Respiratory Cell and Molecular Biology, Volume 58, Issue 2, Page 140-141, February 2018.
http://ift.tt/2GzmulY
Noncoding RNAs: New Players in Pulmonary Medicine and Sarcoidosis
American Journal of Respiratory Cell and Molecular Biology, Volume 58, Issue 2, Page 147-156, February 2018.
http://ift.tt/2rXNqsn
Twist1 in Hypoxia-induced Pulmonary Hypertension through Transforming Growth Factor-β–Smad Signaling
American Journal of Respiratory Cell and Molecular Biology, Volume 58, Issue 2, Page 194-207, February 2018.
http://ift.tt/2GDtoqc
The Long Noncoding RNA LnRPT Is Regulated by PDGF-BB and Modulates the Proliferation of Pulmonary Artery Smooth Muscle Cells
American Journal of Respiratory Cell and Molecular Biology, Volume 58, Issue 2, Page 181-193, February 2018.
http://ift.tt/2rXlzIZ
Reply to: Quantitative Histology Seriously Flawed by Lack of Lung Volume Measurement
American Journal of Respiratory Cell and Molecular Biology, Volume 58, Issue 2, Page 274-275, February 2018.
http://ift.tt/2rXltRD
Dissecting Asthma Transcriptomics: Does Site Matter?
American Journal of Respiratory Cell and Molecular Biology, Volume 58, Issue 2, Page 144-146, February 2018.
http://ift.tt/2GDtnCE
Reduced Clearance of Fungal Spores by Chronic Obstructive Pulmonary Disease GM-CSF– and M-CSF–derived Macrophages
American Journal of Respiratory Cell and Molecular Biology, Volume 58, Issue 2, Page 271-273, February 2018.
http://ift.tt/2rXlpkR
The Long Noncoding RNA LnRPT Puts the Brakes on Pulmonary Artery Smooth Muscle Cell Proliferation
American Journal of Respiratory Cell and Molecular Biology, Volume 58, Issue 2, Page 138-139, February 2018.
http://ift.tt/2GAmemC
The Immunopathologic Effects of Mycoplasma pneumoniae and Community-acquired Respiratory Distress Syndrome Toxin. A Primate Model
American Journal of Respiratory Cell and Molecular Biology, Volume 58, Issue 2, Page 253-260, February 2018.
http://ift.tt/2rXlaGt
Multitissue Transcriptomics Delineates the Diversity of Airway T Cell Functions in Asthma
American Journal of Respiratory Cell and Molecular Biology, Volume 58, Issue 2, Page 261-270, February 2018.
http://ift.tt/2GFkpoM
Quantitative Histology Seriously Flawed by Lack of Lung Volume Measurement
American Journal of Respiratory Cell and Molecular Biology, Volume 58, Issue 2, Page 273-274, February 2018.
http://ift.tt/2rXkEbv
Targeting Hypoxia-Inducible Factor-1α/Pyruvate Dehydrogenase Kinase 1 Axis by Dichloroacetate Suppresses Bleomycin-induced Pulmonary Fibrosis
American Journal of Respiratory Cell and Molecular Biology, Volume 58, Issue 2, Page 216-231, February 2018.
http://ift.tt/2GFkgSg
Syndecan-2 Attenuates Radiation-induced Pulmonary Fibrosis and Inhibits Fibroblast Activation by Regulating PI3K/Akt/ROCK Pathway via CD148
American Journal of Respiratory Cell and Molecular Biology, Volume 58, Issue 2, Page 208-215, February 2018.
http://ift.tt/2rXkuAV
Programmable and Multifunctional DNA-Based Materials for Biomedical Applications
Abstract
DNA encodes the genetic information; recently, it has also become a key player in material science. Given the specific Watson–Crick base-pairing interactions between only four types of nucleotides, well-designed DNA self-assembly can be programmable and predictable. Stem-loops, sticky ends, Holliday junctions, DNA tiles, and lattices are typical motifs for forming DNA-based structures. The oligonucleotides experience thermal annealing in a near-neutral buffer containing a divalent cation (usually Mg2+) to produce a variety of DNA nanostructures. These structures not only show beautiful landscape, but can also be endowed with multifaceted functionalities. This Review begins with the fundamental characterization and evolutionary trajectory of DNA-based artificial structures, but concentrates on their biomedical applications. The coverage spans from controlled drug delivery to high therapeutic profile and accurate diagnosis. A variety of DNA-based materials, including aptamers, hydrogels, origamis, and tetrahedrons, are widely utilized in different biomedical fields. In addition, to achieve better performance and functionality, material hybridization is widely witnessed, and DNA nanostructure modification is also discussed. Although there are impressive advances and high expectations, the development of DNA-based structures/technologies is still hindered by several commonly recognized challenges, such as nuclease instability, lack of pharmacokinetics data, and relatively high synthesis cost.
DNA is an exquisite design of nature, which is endowed with unique properties to assemble into desired structures with multiple functions. This Review discusses classical artificial DNA structures, including aptamers, origamis, and tetrahedrons, but focuses on advanced biomedical applications. Although far from maturity, the use of DNA-based materials is a promising and cutting edge solution to the most challenging biomedical problems.
http://ift.tt/2GBUBtn
Biodistribution, Clearance, and Long-Term Fate of Clinically Relevant Nanomaterials
Abstract
Realization of the immense potential of nanomaterials for biomedical applications will require a thorough understanding of how they interact with cells, tissues, and organs. There is evidence that, depending on their physicochemical properties and subsequent interactions, nanomaterials are indeed taken up by cells. However, the subsequent release and/or intracellular degradation of the materials, transfer to other cells, and/or translocation across tissue barriers are still poorly understood. The involvement of these cellular clearance mechanisms strongly influences the long-term fate of used nanomaterials, especially if one also considers repeated exposure. Several nanomaterials, such as liposomes and iron oxide, gold, or silica nanoparticles, are already approved by the American Food and Drug Administration for clinical trials; however, there is still a huge gap of knowledge concerning their fate in the body. Herein, clinically relevant nanomaterials, their possible modes of exposure, as well as the biological barriers they must overcome to be effective are reviewed. Furthermore, the biodistribution and kinetics of nanomaterials and their modes of clearance are discussed, knowledge of the long-term fates of a selection of nanomaterials is summarized, and the critical points that must be considered for future research are addressed.
Understanding the long-term fate of biomedical nanomaterials is important for the safe-by-design approach to bring these promising systems to the clinic. The current knowledge regarding how the exposure route can affect the biodistribution of various clinically relevant nanomaterials, and thus their interaction with cells, tissues, and organs, is reviewed, with an emphasis on prolonged exposures.
http://ift.tt/2rVYXbH
Antibiotic susceptibilities of indicator bacteria Escherichia coli and Enterococci spp. isolated from ducks in Morogoro Municipality, Tanzania
To estimate the prevalence of antibiotic resistance in indicator bacteria Escherichia coli and Enterococci isolated from duck faeces in Morogoro Municipality, Tanzania.
http://ift.tt/2GDB4J1
Factors associated with timing of umbilical cord clamping in tertiary hospital of Nepal
Delayed umbilical cord clamping (DCC) (≥ 60 s) is recognized to improve iron status and neurodevelopment compared to early umbilical cord clamping. The aim of this study is to identify current umbilical cord c...
http://ift.tt/2nsqpt1
Allogeneic Stem-Cell Transplantation — A T-Cell Balancing ACT
Success in the bone marrow transplantation clinic has always depended on scientific discovery. Before the discovery of histocompatibility antigens, for example, allogeneic hematopoietic stem-cell transplantation (HSCT) was uniformly fatal as a result of overwhelming immunologic catastrophe and…
http://ift.tt/2GF06I4
Correction to: Paragangliomas arise through an autonomous vasculo-angio-neurogenic program inhibited by imatinib
Abstract
The given and family names of two co-authors were incorrect in the published article. The correct spelling should read as: Sampath Chandra Prasad and Vinagolu K Rajasekhar.
http://ift.tt/2FA8LKu
Electrocardiographic Changes in Hypothermia
http://ift.tt/2GEDbMP
Intraspecies polymorphisms of Kluyveromyces marxianus strains from Yaghnob valley
Abstract
In this study, 29 strains of Kluyveromyces marxianus with peculiar genetic and phenotypic traits previously isolated from a fermented goat milk of Yaghnob valley were investigated for chromosome length polymorphism (CLP) by PFGE, adhesion properties and carbon usage by Biolog analysis. Obtained data showed that strains differed in terms of number and size of chromosome bands. The number of bands ranged from 5 to 7, suggesting a probable genome size from 1.4 to 2.6 Mb. Strains showed a certain level of cell surface hydrophobicity ranging from 32% to 77.7%. Strains were also tested for their ability to form a biofilm on polystyrene plates: planktonic cells ranged from 6.3 cfu/mL to 7.95 cfu/mL, while sessile from 7.11 cfu/mL to 8.6 cfu/mL. The strains able to adhere to polystyrene plates were also able to form a mature MAT. Biolog analysis revealed that almost all strains were able to use putrescine, malic acid, α-D lactose, phenylethylamine, β-methyl D-gucoside, and xylose; 5 strains were able to grow on cellobiose and 3 were able to catabolise α-ketobutyric. The obtained data highlighted a number of interesting features underlying the peculiar capacities of these strains for industrial applications.http://ift.tt/2rWqOZf
Beyond nitrogen metabolism: nitric oxide, cyclic-di-GMP and bacterial biofilms
Abstract
The nitrogen cycle pathways are responsible for the circulation of inorganic and organic N-containing molecules in nature. Among these pathways, those involving amino acids, N-oxides and in particular nitric oxide (NO) play strategic roles in the metabolism of microorganisms in natural environments and in host-pathogen interactions. Beyond their role in the N-cycle, amino acids and NO are also signalling molecules able to influence group behaviour in microorganisms and cell-cell communication in multicellular organisms, including humans.In this mini-review, we summarize the role of these compounds in the homeostasis of the bacterial communities called biofilms, commonly found in environmental, industrial and medical settings. Biofilms are difficult to eradicate since they are highly resistant to antimicrobials and to the host immune system. We highlight the effect of amino acids such as glutamate, glutamine and arginine and of NO on the signalling pathways involved in the metabolism of 3', 5'-cyclic diguanylic acid (c-di-GMP), a master regulator of motility, attachment and group behaviour in bacteria. The study of the metabolic routes involving these N-containing compounds represents an attractive topic to identify targets for biofilm control in both natural and medical settings.http://ift.tt/2GDssSH
Diversification of Pseudomonas aeruginosa within the cystic fibrosis lung and its effects on antibiotic resistance
Abstract
The evolution and diversification of bacterial pathogens within human hosts represent potential barriers to the diagnosis and treatment of life-threatening infections. Tremendous genetic and phenotypic diversity is characteristic of host adaptation in strains of Pseudomonas aeruginosa that infect the airways of individuals with chronic lung diseases and prove to be extremely difficult to eradicate. In this MiniReview, we examine recent advances in understanding within-host diversity and antimicrobial resistance in P. aeruginosa populations from the lower airways of individuals with the fatal genetic disease cystic fibrosis and the potential impacts that this diversity may have on detecting and interpreting antimicrobial susceptibility within these populations.http://ift.tt/2s1q4SA
Tisagenlecleucel in Children and Young Adults with B-Cell Lymphoblastic Leukemia
Tisagenlecleucel (formerly CTL019), an anti-CD19 chimeric antigen receptor (CAR) T-cell therapy, is under investigation in patients with relapsed or refractory B-cell cancers, including B-cell acute lymphoblastic leukemia (ALL). Results from a single-center phase 1–2a study of tisagenlecleucel…
http://ift.tt/2rYhsfI
Allogeneic Stem-Cell Transplantation — A T-Cell Balancing ACT
Success in the bone marrow transplantation clinic has always depended on scientific discovery. Before the discovery of histocompatibility antigens, for example, allogeneic hematopoietic stem-cell transplantation (HSCT) was uniformly fatal as a result of overwhelming immunologic catastrophe and…
http://ift.tt/2GF06I4
Organic Light-Emitting Diodes: Achieving Nearly 30% External Quantum Efficiency for Orange–Red Organic Light Emitting Diodes by Employing Thermally Activated Delayed Fluorescence Emitters Composed of 1,8-Naphthalimide-Acridine Hybrids (Adv. Mater. 5/2018)
In article number 1704961, Shaolong Gong, Chung-Chih Wu, Chuluo Yang, and co-workers present orange-red organic light-emitting diodes (OLEDs) with external quantum efficiencies of up to 29.2% through employing thermally activated delayed fluorescence emitters of a 1,8-naphthalimide–acridine hybrid. The relatively high photoluminescence quantum yield and horizontally oriented emitting dipoles of these emitters combined with the influence of the microcavity effect are verified to support the record-high efficiency.
http://ift.tt/2DWwt72
Graphene Nanoinks: A Water-Processable and Bioactive Multivalent Graphene Nanoink for Highly Flexible Bioelectronic Films and Nanofibers (Adv. Mater. 5/2018)
A water-processable and bioactive multivalent graphene nanoink featured with a well-defined 2D flat morphology is synthesized and studied by Chong Cheng, Rainer Haag, and co-workers in article number 1705452. This new graphene nanoink can be easily coated/brushed onto bioelectronic materials and provides high mechanical flexibility, good electrochemical activity, and high cellular compatibility and orientation.
http://ift.tt/2E7VI60
Battery Cathodes: Controllable Solid Electrolyte Interphase in Nickel-Rich Cathodes by an Electrochemical Rearrangement for Stable Lithium-Ion Batteries (Adv. Mater. 5/2018)
In article number 1704309, Minjoon Park, Jaephil Cho, and co-workers develop a nickel-rich cathode with an artificial solid electrolyte interphase (SEI) layer that can be electrochemically rearranged along grain boundaries. The cathode with the incorporated artificial SEI layer exhibits not only outstanding electrochemical performance at high temperature, and even at high cut-off voltage, but also structural integrity after electrochemical testing. These results provide a rational approach for the development of advanced cathode materials.
http://ift.tt/2FwXr1B
Bionanostructures: Bioinspired Flexible and Tough Layered Peptide Crystals (Adv. Mater. 5/2018)
Scanning electron microscopy (SEM) studies of laminated self-assembled N-capped diphenylalanine crystals are presented by Lihi Adler-Abramovich, Ehud Gazit, and co-workers in article number 1704551. These crystals exhibit well-ordered crystal packing and diffraction of sub-Ångstrom resolution, yet display an exceptionally flexible nature. The combination of strength, toughness, and flexibility can be explained in terms of weak interactions between the rigid crystal layers, which are presented in the SEM image shown.
http://ift.tt/2E7VvQg
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Αλέξανδρος Γ. Σφακιανάκης Medicine by Alexandros G. Sfakianakis,Anapafseos 5 Agios Nikolaos 72100 Crete Greece,00302841026182,0030693260717...
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Alimentary Pharmacology &Therapeutics, EarlyView. https://ift.tt/2qECBIJ
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heory of COVID-19 pathogenesis Publication date: November 2020Source: Medical Hypotheses, Volume 144Author(s): Yuichiro J. Suzuki ScienceD...
