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- Periprocedural management of patients with subarac...
- An update on regional analgesia for rib fractures
- Anesthesia for stroke rescue
- Intraoperative neurophysiological monitoring in ne...
- Outcomes of regional anesthesia in cancer patients
- Rapid Onset of a Painful, Ulcerated Facial Lesion ...
- Cover
- News
- In the Literature
- Rapid Onset of a Painful, Ulcerated Facial Lesion ...
- Microbial responses to transient shock loads of qu...
- Comprehensive investigation of a dye-decolorizing ...
- Digital biomarkers of spine and musculoskeletal di...
- Severe Hyperkyphosis Reduces the Aerobic Capacity ...
- The Reliability of Motor Evoked Potentials to Pred...
- Goat pasteurellosis: serological analysis of circu...
- Comparing the order of the London Measure of Unpla...
- Pulmonary nocardiosis masquerading renascence of t...
- Challenge in direct Spoligotyping of Mycobacterium...
- Correcting the literature: Improvement trends seen...
- “Good Fashion is Evolution, Not Revolution” - Meth...
- Meet Our Editorial Board Member
- Radio-Modulatory Potential of Caffeic Acid Pheneth...
- Recent Development of Sulfonyl or Sulfonamide Hybr...
- Factors associated with outcomes in traumatic card...
- BRAF/MEK Combo Approved for Melanoma [News in Brief]
- Medical Care Costs Associated with Genital Warts f...
- Genome Report: Whole Genome Sequence of the Parasi...
- Rapid Low-Cost Assembly of the Drosophila melanoga...
- Management of Subdural Hematomas: Part II. Surgica...
- Cytokines Produced by Dendritic Cells Administered...
- Vitamin D supplementation and survival of patients...
- Cachectic Cancer Patients: Immune to Check-point I...
- Trials Supporting FDA Approval of Breakthrough Dru...
- High Frequency of Digital Media Use Linked to ADHD...
- Problem Solving Helps Prevent Depression in Low-In...
- Alternative Payment Models Should Include Precisio...
- FDA: Some Rx Drugs May Become Available Without Se...
- Roles of human epidermal growth factor receptor fa...
- Tumor-infiltrating lymphocytes associate with outc...
- Predicting Enrollment in Multidisciplinary Clinica...
- Moving beyond race and ethnicity to understand the...
- Diuretics in newborns born extremely premature: th...
- The Role of Gender in Publication in The Journal o...
- National Trends in Hospitalization for Fever and N...
- Constipation Burden in Children with Autism Spectr...
- Intestinal Involvement in Kawasaki Disease
- The Complexities of Ascertaining Public Preference...
- Clinical Characteristics and Risk Factors for Deve...
- Can Real World Evidence on Body Mass Index Traject...
- Appropriateness in prescribing PPIs: a position pa...
- Management of hilum infiltrating tumors of the liv...
- Unexpected intestinal bypass
- Diabetes is associated with advanced fibrosis and ...
- Self-tracking of Physical Activity in People With ...
- Immunoglobulin-induced aseptic meningitis: a case ...
- Psychometric Properties of the Canadian Nurse Info...
- ANI Steering Committee Welcomes New Members
- Automated Deterioration Detection Using Electronic...
- Applying Machine-Learning Techniques to Build Self...
- Erratum to: Usage and Usability of a Web-based Pro...
- Development of the Canadian Nurse Informatics Comp...
- Impact of Adoption of a Comprehensive Electronic H...
- Impact of Adoption of a Comprehensive Electronic H...
- Prevalence of human anelloviruses in Romanian heal...
- Epidemiological characterization of respiratory tr...
- ‘Being able to bear a child’: Insights from Zimbab...
- Midwives’ personal use of complementary and altern...
- Process evaluation of the midwifery initiated oral...
- Maternal, prenatal and traditional practice factor...
- A multi-layered poroelastic slab model under cycli...
- Neisseria Gonorrhoae and their antimicrobial susce...
- Collateral damage of using colistin in hospitalize...
- Calibration-free In Vitro Quantification of Protei...
- The Identification of Sea Lamprey Pheromones Using...
- Visualizing the Interaction Between the Qdot-label...
- Isolation, Expansion, and Adipogenic Induction of ...
- Visualization of DNA Compaction in Cyanobacteria b...
- Cataract Surgery May Cut Risk of Serious Car Accid...
- FDA Establishes New Task Force on Drug Shortages
- Shared Decision-Making Approach to Zika Best for T...
- Brief Safety Plan Intervention in ER Can Cut Suici...
- Immediate Monitoring With ECG Patch Ups A-Fib Diag...
- Preoperative Opioids Used by 23.1 Percent of Surgi...
- Evidence of Clinical Inertia in Management of T2DM
- Most Adults Perceive Nicotine Exposure As Harmful ...
- Higher Risk of In-Situ Breast CA, Ovarian Tumors W...
- Multiple Factors to Consider When Selecting NSAID ...
- Study Links Children’s Eye-Hand Coordination with ...
- Detection of Mitochondria Membrane Potential to St...
- PIM1 overexpression in T-cell lymphomas protects t...
- Proton pump inhibitors increase the risk of cholec...
- NAEMSP applauds formation of FDA drug shortages ta...
- Ethnobotanical Study of Medicinal Plants Used to T...
- How to deal with two-year molars
- Frontmatter
- Exploratory cell dynamics: a sense of touch for ce...
- Sphingolipid metabolism – an ambiguous regulator o...
- Insulin-like signaling within and beyond metazoans
- Novel approach to quorum quenching: rational desig...
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Αναζήτηση αυτού του ιστολογίου
Τρίτη 17 Ιουλίου 2018
Periprocedural management of patients with subarachnoid hemorrhage
https://ift.tt/2zXY2M3
An update on regional analgesia for rib fractures
https://ift.tt/2mrV6h2
Anesthesia for stroke rescue
https://ift.tt/2zKyTE8
Intraoperative neurophysiological monitoring in neuroanesthesia
https://ift.tt/2mmLlAy
Outcomes of regional anesthesia in cancer patients
https://ift.tt/2zQWi76
Microbial responses to transient shock loads of quaternary ammonium compounds with different length of alkyl chain in a membrane bioreactor
Extensive applications of quaternary ammonium compounds (QACs) in household and industrial products inevitably lead to their release into wastewaters; however, little attention has been paid to the acute effec...
https://ift.tt/2LkbNsF
Comprehensive investigation of a dye-decolorizing peroxidase and a manganese peroxidase from Irpex lacteus F17, a lignin-degrading basidiomycete
Irpex lacteus F17 is well-known for its ability to degrade recalcitrant aromatic pollutants, which mainly results from the action of the manganese peroxidase (MnP) that it is able to produce. Recently, the genome...
https://ift.tt/2JwkgUO
Digital biomarkers of spine and musculoskeletal disease from accelerometers: Defining phenotypes of free-living physical activity in knee osteoarthritis and lumbar spinal stenosis
Publication date: Available online 17 July 2018
Source: The Spine Journal
Author(s): Christy Tomkins-Lane, Justin Norden, Aman Sinha, Richard Hu, Matthew Smuck
Abstract
Background Context
Lumbar spinal stenosis (LSS) and knee osteoarthritis (OA) are two of the leading causes of disability worldwide. In order to provide disease-specific prescriptions for physical activity, there is a clear need to better understand physical activity in daily life (performance)in these populations.
Purpose
To discover performance phenotypes for LSS and OA by applying novel analytic methods to accelerometry data. Specific objectives include 1) identify characteristic features (phenotypes) of free-living physical activity unique to individuals with LSS and OA, and 2) determine which features can best differentiate between these conditions.
Study Design & Setting
Leveraging data from 3 existing cross-sectional cohorts, accelerometry signal feature characterization and selection was performed in a computational laboratory.
Patient Sample
Data from a total of 4028 individuals were analyzed from the following 3 datasets: Lumbar Spinal Stenosis Accelerometry Database (LSS, n=75); Osteoarthritis Initiative (OA, n=1950); and the 2003-4 National Health and Nutrition Examination Survey (Pain Free Controls, n=2003).
Methods
In order to characterize the accelerometry signals, data were examined using 1) standard intervals for counts/minute from Freedson et al., and 2) the Physical Performance intervals for mobility-limited pain populations. From this, 42 novel accelerometry features were defined and evaluated for significance in discriminating between the groups (LSS, OA, Controls) in order to then determine which sparse set of features best differentiates between the groups. These sparse sets of features defined the performance phenotypes.
Outcome Measures
Accelerometry features and their ability to differentiate between individuals with LSS, OA, and Controls.
Results
Given age and gender, classification rates were at least 80% accurate (pairwise) between diseased and pain-free populations (LSS vs. Controls and OA vs. Controls). The most important features to distinguish between disease groups corresponded to measures in the light and sedentary activity intervals. The more subtle classification between diseased populations (LSS vs. OA) was 72% accurate, with light and moderate activity providing the prominent distinguishing features.
Conclusions
We describe the discovery of performance phenotypes of LSS and OA from accelerometry data, revealed through a novel set of features that characterize daily patterns of movement in people with LSS and OA. These performance phenotypes provide a new method for analyzing free living physical activity (performance) in LSS and OA, and provide the groundwork for more personalized approaches to measuring and improving function.
https://ift.tt/2zQ1loi
Severe Hyperkyphosis Reduces the Aerobic Capacity and Maximal Exercise Tolerance in Patients with Scheuermann Disease
Publication date: Available online 17 July 2018
Source: The Spine Journal
Author(s): Alejandro Lorente, Carlos Barrios, Rafael Lorente, Rocío Tamariz, Jesús Burgos
Abstract
BACKGROUND CONTEXT
The evaluation of ventilatory functional restrictions during a maximal exercise tolerance test in patients with Scheuermann disease has never been described.
PURPOSE
This study evaluated the respiratory functional capacity of patients with Scheuermann disease compared to healthy adolescents matched in age.
STUDY DESIGN/SETTING
Prospective comparative study.
PATIENTS SAMPLE
Forty-one consecutive adolescents with Scheuermann hyperkyphosis (SK) and 20 healthy controls matched in age were included in the study.
OUTCOME MEASURES
Basal spirometry and dynamic ventilatory parameters were measured during a maximal cardiopulmonary exercise tolerance test. Heart rate, oxygen saturation (SatO2), maximum oxygen uptake (VO2 max), quotient between ventilation and volume of exhaled carbon dioxide (VE/CO2), respiratory exchange rate (RER), ventilatory capacity at maximal exercise (VEmax), and test duration were recorded at initium and at maximal exercise.
METHODS
The exercise tolerance test was completed to exhaustion using a standard Bruce protocol on a ramp treadmill. Comparisons of quantitative variables between SK and control group were analyzed by statistical nonparametric test. The correlations between the magnitude of the thoracic kyphosis and both the VO2 max/kg and VEmax of the SK group were also analyzed. No funds were required. The authors have no conflicts of interests.
RESULTS
Patients with SK started the test with a higher heart rate (p<0.01) and reached exhaustion with a lower heart rate (p<0.05) than healthy controls. At maximal exercise, the SatO2 was declined in Scheuermann patients compared to healthy subjects (p<0.05). The maximal aerobic power (VO2max) was greater in healthy controls than in hyperkyphotic patients (50.0 ± 6.7 vs. 43.4 ± 11.3 mL/kg/minute; p<0.05). There was an inverse correlation between the increase in the magnitude of thoracic kyphosis and the deterioration of the maximal aerobic power. VO2max and VEmax were severely deteriorated in patients with more than 75° kyphosis. Patients with >75° thoracic kyphosis also showed an impairment in their cardiovascular efficiency as measured by the HR/VO2 quotient. The limited tolerance to the exercise in SK patients was reflected by a shorter duration of the exercise test and a lower energy cost measured in METS (metabolic equivalents) as compared to healthy controls.
CONCLUSIONS
Patients with severe hyperkyphosis (>75°) show significant respiratory inefficiency together with a lower ventilation capacity and lower VO2max. There is an inverse correlation between the increase in the magnitude of thoracic kyphosis and the deterioration of the maximal aerobic power.
https://ift.tt/2mnyiia
The Reliability of Motor Evoked Potentials to Predict Dorsiflexion Injuries During Lumbosacral Deformity Surgery: Importance of Multiple Myotomal Monitoring
Publication date: Available online 17 July 2018
Source: The Spine Journal
Author(s): Jeremy A. Lieberman, Russ Lyon, Paul Jasiukaitis, Sigurd H. Berven, Shane Burch, John Feiner
ABSTRACT
Study Design
Case-control analysis of transcranial motor evoked potential (MEP) responses and clinical outcome.
Objective
To determine the sensitivity and specificity of MEPs to predict isolated nerve root injury causing dorsiflexion weakness in selected patients having complex lumbar spine surgery.
Summary of Background Data
The surgical correction of distal lumbar spine deformity involves significant risk for damage to neural structures that control muscles of ankle and toe dorsiflexion. Procedures often include vertebral translation, interbody fusion, and posterior-based osteotomies. The benefit of using MEP monitoring to predict dorsiflexion weakness has not been well-established. The purpose of this paper is to describe the relationship between neural complications from lumbar surgery and intraoperative MEP changes.
Methods
Included were 542 neurologically intact patients who underwent posterior spinal fusion for the correction of distal lumbar deformity. Two myotomes, including tibialis anterior (TA) and extensor hallucis longus (EHL), were monitored. MEP and free-running electromyography data were assessed in each patient. Cases of new dorsiflexion weakness noted postoperatively were identified. Data in case and control patients were compared. There was no direct funding for this work. The Department of Anesthesiology and Perioperative Care provides salary support for authors one and six. Authors two and three report employment in the field of intraoperative neurophysiological monitoring as a study-specific conflict of interest.
Results
Twenty-five patients (cases) developed dorsiflexion weakness. MEP amplitude decreased in the injured myotomes by an average of 65±21% (TA) and 60±26% (EHL), which was significantly greater than the contralateral uninjured side or for control subjects. (P<0.01) Receiver operator characteristic (ROC) curves showed high sensitivity, specificity, and predictive value for changes in MEP amplitude using either the TA or EHL. Analysis of MEP changes to either TA and EHL yielded a superior ROC curve. Net reclassification improvement analysis showed assessing MEP changes to both TA and EHL statistically improved the predictability of injury.
Conclusion
The use of MEP amplitude change is highly sensitive and specific to predict a new postoperative dorsiflexion injury. Monitoring two myotomes (both TA and EHL) is superior to relying on MEP changes from a single myotome. EMG activity was less accurate but compliments MEP use. Additional studies are needed to define optimal intraoperative MEP warning thresholds.
https://ift.tt/2zM1VmV
Goat pasteurellosis: serological analysis of circulating Pasteurella serotypes in Tanqua Aberegelle and Kola Tembien Districts, Northern Ethiopia
A cross-sectional study was employed with the aim to explore the serological status of goats; we evaluated the presence of serum antibodies of the circulating serotypes of the genus Pasteurella. A total of 124 se...
https://ift.tt/2uJbBZP
Comparing the order of the London Measure of Unplanned Pregnancy and the Demographic and Health Survey question on pregnancy intention in a single group of postnatal women in Malawi - the effect of question order on assessment of pregnancy intention
To investigate the effect of question order on women's responses to the London Measure of Unplanned Pregnancy (LMUP) or the pregnancy intention question of the Demographic and Health Survey (DHS) when both are...
https://ift.tt/2LhbfE0
Pulmonary nocardiosis masquerading renascence of tuberculosis in an immunocompetent host: a case report from Nepal
Pulmonary nocardiosis is an opportunistic infection in an immunocompromised patient; however, often neglected in the immunocompetent patient from the diagnosis considerations.
https://ift.tt/2uJdWUq
Challenge in direct Spoligotyping of Mycobacterium tuberculosis: a problematic issue in the region with high prevalence of polyclonal infections
Based on our recent studies the prevalence of polyclonal infection in tuberculosis clinical specimens is more than 50% in Tehran, Iran. With this background, Spoligotyping was performed on clinical specimens a...
https://ift.tt/2Lkl8AA
Correcting the literature: Improvement trends seen in contents of retraction notices
To analyse retraction notices from 2016 and compare their quality to the 2008 notices.
https://ift.tt/2uQawzx
“Good Fashion is Evolution, Not Revolution” - Methods to Enhance Existing Anticancer Medicines, Primarily with the Use of Transition Metal
The constant search for successful cancer therapies lasts for decades. Apart from the huge scientific effort and enormous sum of spent money, only a small amount of newly developed medicines move into clinical use (only 94 registered anticancer drugs in the last 12 years). Anticancer regimes are still overcome by drugs invented over 50 years ago such as cisplatin and doxorubicin. Significant progress in the development of improved anticancer drugs was made due to multiple studies on the relationship between the molecular structure of chemical compounds and their cytostatic activity. A number of ligands (mainly organic) with quite effective anticancer properties are known, but they show insufficient activity, selectivity and multidrug resistance. Formation of transition metal – ligand complexes (with proven anticancer effect) changes the properties of the latter. The factors that affect the cytotoxic properties of metal complexes are: the type of ligand and metal, the nature of the connection between metal and ligand, and the distribution of electronic charge density in the formed complexes. Here, we report the recent efforts to improve existing compounds with confirmed anticancer activity. They seem to be unappreciated as their effects appear to be less spectacular than that of targeted anticancer drugs (i.e. based on antibodies or small RNAs).
https://ift.tt/2uQ0HBF
Radio-Modulatory Potential of Caffeic Acid Phenethyl Ester: A Therapeutic Perspective
Background: Use of natural agents is an upcoming area of research in cancer biology. Caffeic acid phenethyl ester (CAPE) has received great attention because of its therapeutic potential in various conditions including cancer. It is an active/abundant component of propolis, a honey bee hive product produced by bees using their enzyme-rich digestive secretions on resinous mix, bee wax and pollen from plants. It is used to protect the beehive against bacteria and other infections. Therefore a literature survey was done to understand the therapeutic potential of this compound. Although a lot of work has been done on chemotherapeutic aspects of CAPE and many reviews were available, yet its role as a radiomodulator was not clear.
Objective: The objective of the review was to collect data on role of Caffeic acid phenethyl ester as radioprotector and /or sensitizer to evaluate its potential as modulator of radiation effects during cancer therapy.
Methods: For literature survey, Pubmed and Google search engines were used. Data were collected up to August 2017. PubMed advanced search builder showed 845 papers on CAPE. This search was further narrowed down to synthesis, bioavailability, CAPE derivatives, radioprotective and radiosensitizing effects of CAPE.
Results: This review focused on the differential radiomodulatory effects of CAPE in normal and cancer cells. Besides chemistry and bioavailability, it's potential as a therapeutic agent against radiation induced damage was also evaluated.
Conclusion: CAPE was found to act both as radioprotector and radiosensitizer. Depending on the tissue type it can modulate the radiation response by following different mechanisms.
https://ift.tt/2uIuzQi
Recent Development of Sulfonyl or Sulfonamide Hybrids as Potential Anticancer Agents: A Key Review
Cancer is the second leading cause of death worldwide. There is always a huge demand for novel anticancer drugs and diverse new natural or synthetic compounds are developed continuously by scientists. Presently, a large number of drugs in clinical practice have showed pervasive side effect and multidrug resistance. Sulfonyl or sulfonamide hybrids became one of the most attractive subjects due to their broad spectrum of pharmacological activities. Sulfonyl hybrids were broadly explored for their anticancer activities and it was found that they possess minimum side effect along with multi-drug resistance activity. This review describes the most recent applications of sulfonyl hybrid analogues in anticancer drug discovery and further discusses the mechanistic insights, structure-activity relationships and molecular docking studies for the potent derivatives.
https://ift.tt/2LeyxKN
Factors associated with outcomes in traumatic cardiac arrest patients without prehospital return of spontaneous circulation
Publication date: Available online 17 July 2018
Source: Injury
Author(s): Yi-Chuan Chen, Kai-Hsiang Wu, Kuang-Yu Hsiao, Ming-Szu Hung, Yi-Chen Lai, Yuan-Shun Chen, Chih-Yao Chang
Abstract
Background
Prognostic factors for the outcomes in traumatic cardiac arrest (TCA) patients transported to hospitals without prehospital return of spontaneous circulation (ROSC) remain uncertain. The aim of this study is to investigate factors associated with outcomes in TCA patients without prehospital ROSC.
Methods
We conducted a retrospective cohort study using a multi-institutional, 5-year database. Only TCA patients without prehospital ROSC were included. The primary outcome was ROSC in the emergency department (ED), and the secondary outcome was 30-day survival. Logistic regression analysis was performed to determine the factors associated with primary and secondary outcomes.
Results
Among 463 TCA patients, 73 (16%) had ROSC during ED resuscitation, and among those with sustained ROSC, 10 (14%) survived for at least 30 days. Injury severity score ≧ 16 (OR, 0.06; 95% CI: 0.02–0.20), trauma center admission (OR, 2.69; 95% CI: 1.03-7.03), length of ED resuscitation (OR, 0.98; 95% CI: 0.96-0.99), and total resuscitation length > 20 minutes (OR, 0.21; 95% CI: 0.08–0.54) were associated with ROSC.
Conclusions
In TCA patients transported to hospitals without prehospital ROSC, resuscitation attempts could be beneficial. We should aim to resuscitate patients as soon as possible with appropriate treatments for trauma patients, early activation of trauma team, and then, as a result, shorter resuscitation time will be achieved.
https://ift.tt/2L3VKzN
BRAF/MEK Combo Approved for Melanoma [News in Brief]
Encorafenib/binimetinib an option for patients with metastatic or inoperable disease with BRAF mutation.
https://ift.tt/2uGbmhV
Medical Care Costs Associated with Genital Warts for Commercially Insured US Patients
Abstract
Introduction
Genital warts are caused by infection with human papillomavirus (HPV) and are associated with significant morbidity. Primary prevention of genital warts is possible through HPV vaccination, but vaccination rates remain low in the USA. When deciding to implement HPV vaccination programs, public health officials and policy makers rely on cost-effectiveness studies that accurately reflect costs associated with morbidity and mortality. However, previous information on the cost of treating genital warts was outdated.
Objectives
We estimated the mean direct medical care costs associated with genital warts in the USA.
Methods
This was a retrospective case–control study of patients diagnosed with genital warts and matched controls. We used commercial healthcare claims data from 2011 through 2014 to estimate total 1- and 2-year costs from date of diagnosis. We used a generalized linear model to identify factors associated with monthly costs.
Results
We identified 34,686 eligible cases of genital warts during the period 2011–2014. The first 2-year mean direct medical cost differences between cases and controls were US$6737 for the USA. Costs were significantly higher in the first 3 months following diagnosis and were higher among older individuals, women, those with co-morbidities or psychiatric illnesses, and those located in the south and southwest USA.
Conclusions
The mean direct cost of treating genital warts is approximately US$6700 in the first 2 years after diagnosis in the USA. These data can assist policy makers in decisions with respect to allocation of resources to implement HPV vaccine programs.
https://ift.tt/2LjilHV
Genome Report: Whole Genome Sequence of the Parasitoid Wasp Microplitis demolitor That Harbors an Endogenous Virus Mutualist
Microplitis demolitor(Hymenoptera: Braconidae) is a parasitoid used as a biological control agent to control larval-stage Lepidoptera and serves as a model for studying the function and evolution of symbiotic viruses in the genus Bracovirus. Here we present the M. demolitor genome (assembly version 2.0), with a genome size of 241 Mb, and a N50 scaffold and contig size of 1.1 Mb and 14 Kb, respectively. Using RNA-Seq data and manual annotation of genes of viral origin, we produced a high-quality gene set that includes 18,586 eukaryotic and 171 virus-derived protein-coding genes. Bracoviruses are dsDNA viruses with unusual genome architecture, in which the viral genome is integrated into the wasp genome and is comprised of two distinct components: proviral segments that are amplified, circularized, and packaged into virions for export into the wasp's host via oviposition; and replication genes. This genome assembly revealed that at least two scaffolds contain both nudivirus-like genes and proviral segments, demonstrating that at least some of these components are near each other in the genome on a single chromosome. The updated assembly and annotation are available in several publicly accessible databases; including the National Center for Biotechnology Information and the Ag Data Commons. In addition, all raw sequence data available for M. demolitor have been consolidated and are available for visualization at the i5k Workspace. This whole genome assembly and annotation represents the only genome-scale, annotated assembly from the lineage of parasitoid wasps that has associations with bracoviruses (the 'microgastroid complex'), providing important baseline knowledge about the architecture of co-opted virus symbiont genomes. have been consolidated and are available for visualization at the i5k Workspace. This whole genome assembly and annotation represents the only genome-scale, annotated assembly from the lineage of parasitoid wasps that has associations with bracoviruses (the 'microgastroid complex'), providing important baseline knowledge about the architecture of co-opted virus symbiont genomes.
https://ift.tt/2LdYdXV
Rapid Low-Cost Assembly of the Drosophila melanogaster Reference Genome Using Low-Coverage, Long-Read Sequencing
Accurate and comprehensive characterization of genetic variation is essential for deciphering the genetic basis of diseases and other phenotypes. A vast amount of genetic variation stems from large-scale sequence changes arising from the duplication, deletion, inversion, and translocation of sequences. In the past 10 years, high-throughput short reads have greatly expanded our ability to assay sequence variation due to single nucleotide polymorphisms. However, a recent de novo assembly of a second Drosophila melanogaster reference genome has revealed that short read genotyping methods miss hundreds of structural variants, including those affecting phenotypes. While genomes assembled using high-coverage long reads can achieve high levels of contiguity and completeness, concerns about cost, errors, and low yield have limited widespread adoption of such sequencing approaches. Here we resequenced the reference strain of D. melanogaster (ISO1) on a single Oxford Nanopore MinION flow cell run for 24 hours. Using only reads longer than 1 kb or with at least 30x coverage, we assembled a highly contiguous de novo genome. The addition of inexpensive paired reads and subsequent scaffolding using an optical map technology achieved an assembly with completeness and contiguity comparable to the D. melanogaster reference assembly. Comparison of our assembly to the reference assembly of ISO1 uncovered a number of structural variants (SVs), including novel LTR transposable element insertions and duplications affecting genes with developmental, behavioral, and metabolic functions. Collectively, these SVs provide a snapshot of the dynamics of genome evolution. Furthermore, our assembly and comparison to the D. melanogaster reference genome demonstrates that high-quality de novo assembly of reference genomes and comprehensive variant discovery using such assemblies are now possible by a single lab for under $1,000 (USD).
https://ift.tt/2JBxP5c
Management of Subdural Hematomas: Part II. Surgical Management of Subdural Hematomas
Abstract
Purpose of review
Management of patients with subdural hematomas starts with Emergency Neurological Life Support guidelines. Patients with acute or chronic subdural hematomas (SDHs) associated with rapidly deteriorating neurologic exam, unilaterally or bilaterally dilated nonreactive pupils, and extensor posturing are considered imminently surgical; likewise, SDHs more than 10 mm in size or those associated with more than 5-mm midline shift are deemed operative.
Recent findings
While twist drill craniostomy and placement of subdural evacuating vport system (SEPS) are quick, bedside procedures completed under local anesthesia and appropriate for patients with chronic SDH or patients that cannot tolerate anesthesia, these techniques are not optimal for patients with acute SDH or chronic SDH with septations. Burr hole SDH evacuation under conscious sedation or general anesthesia is an analogous technique; however, it requires basic surgical equipment and operating room staff, with a focus on a closed system with burr hole followed by rapid drain placement to avoid introduction of air into the subdural space, or multiple burr holes with extensive irrigation to reduce pneumocephalus and continue SDH evacuation via drain for several days. Acute SDH associated with significant mass effect and cerebral edema requires aggressive decompression via craniotomy with clot evacuation and frequently a craniectomy. Chronic SDHs that fail conservative management and progress clinically or radiographically are addressed with craniotomy with or without membranectomy.
Summary
Surgical SDH management is variable depending on its characteristics and etiology, patient's functional status, comorbidities, goals of care, institutional preferences, and availability of specialized surgical equipment and adjunct therapies. Rapid access to surgical suites and trained staff to address surgical hemorrhages in a timely manner, with appropriate post-operative care by a specialized team including neurosurgeons and neurointensivists, is of paramount importance for successful patient outcomes. Here, we review various aspects of surgical SDH management.
https://ift.tt/2uHp9ox
Cytokines Produced by Dendritic Cells Administered Intratumorally Correlate with Clinical Outcome in Patients with Diverse Cancers
Purpose: Dendritic cells (DC) initiate adaptive immune responses through the uptake and presentation of antigenic material. In preclinical studies, intratumorally injected activated DCs (aDCs; DCVax-Direct) were superior to immature DCs in rejecting tumors from mice.
Experimental Design: This single-arm, open-label phase I clinical trial evaluated the safety and efficacy of aDCs, administered intratumorally, in patients with solid tumors. Three dose levels (2 million, 6 million, and 15 million aDCs per injection) were tested using a standard 3 + 3 dose-escalation trial design. Feasibility, immunogenicity, changes to the tumor microenvironment after direct injection, and survival were evaluated. We also investigated cytokine production of aDCs prior to injection.
Results: In total, 39 of the 40 enrolled patients were evaluable. The injections of aDCs were well tolerated with no dose-limiting toxicities. Increased lymphocyte infiltration was observed in 54% of assessed patients. Stable disease (SD; best response) at week 8 was associated with increased overall survival. Increased secretion of interleukin (IL)-8 and IL12p40 by aDCs was significantly associated with survival (P = 0.023 and 0.024, respectively). Increased TNFα levels correlated positively with SD at week 8 (P < 0.01).
Conclusions: Intratumoral aDC injections were feasible and safe. Increased production of specific cytokines was correlated with SD and prolonged survival, demonstrating a link between the functional profile of aDCs prior to injection and patient outcomes. Clin Cancer Res; 1–12. ©2018 AACR.
https://ift.tt/2JwtJLH
Vitamin D supplementation and survival of patients with non-small-cell lung cancer: A randomized, double-blind, placebo-controlled trial
Purpose: Higher serum 25-hydroxyvitamin D (25(OH)D) levels are reportedly associated with better survival in early-stage non-small-cell lung cancer (NSCLC). Therefore, whether vitamin D supplementation can improve the prognosis of NSCLC patients was examined (UMIN000001869). Experimental Design: A randomized, double-blind trial comparing vitamin D supplements (1,200 IU/day) with placebo for 1 year after operation was conducted. The primary and secondary outcomes were relapse-free survival (RFS) and overall survival (OS), respectively. Pre-specified subgroup analyses were performed with stratification by stage (early vs. advanced), pathology (adenocarcinoma vs. others), and 25(OH)D levels (low, <20 ng/ml vs. high, ≥20 ng/ml). Polymorphisms of vitamin D receptor (VDR) and vitamin D binding protein (DBP) and survival were also examined. Results: NSCLC patients (n=155) were randomly assigned to receive vitamin D (n=77) or placebo (n=78) and followed for a median of 3.3 years. Relapse and death occurred in 40 (28%) and 24 (17%) patients, respectively. In the total study population, no significant difference in either RFS or OS was seen with vitamin D compared to the placebo group. However, by restricting the analysis to the subgroup with early-stage adenocarcinoma with low 25(OH)D, the vitamin D group showed significantly better 5-year RFS (86% vs. 58%, P=0.04) and OS (92% vs. 56%, P=0.02) than the placebo group. Among the examined polymorphisms, DBP1 (rs7041) TT and CDX2 (rs11568820) AA/AG genotypes were markers of better prognosis, even with multivariate adjustment. Conclusions: In NSCLC patients, vitamin D supplementation may improve survival of early-stage lung adenocarcinoma patients with lower 25(OH)D levels.
https://ift.tt/2L3cV4t
Cachectic Cancer Patients: Immune to Check-point Inhibitor Therapy?
Immune check-point inhibition is dramatically improving patient outcomes in diverse cancers, many of which responded poorly to traditional cytotoxic agents. Drivers of heterogeneous response to immune check-point therapy are poorly characterized. Cachectic cancer patients exhibit elevated pembrolizumab clearance and poor response highlighting the immense therapeutic challenge posed by cancer cachexia.
https://ift.tt/2JwtJeF
Trials Supporting FDA Approval of Breakthrough Drugs Examined
TUESDAY, July 17, 2018 -- Pivotal trials supporting U.S. Food and Drug Administration approvals granted Breakthrough Therapy designation often lack randomization, double-blinding, and control groups, according to a research letter published in the...
https://ift.tt/2NovNHV
High Frequency of Digital Media Use Linked to ADHD Symptoms
TUESDAY, July 17, 2018 -- There is a modest, but statistically significant, association between higher frequency of digital media use and subsequent symptoms of attention-deficit/hyperactivity disorder (ADHD) among adolescents, according to a study...
https://ift.tt/2NXW013
Problem Solving Helps Prevent Depression in Low-Income Moms
TUESDAY, July 17, 2018 -- Problem-solving education (PSE) is effective at preventing depressive symptoms among low-income mothers, according to a study published online June 29 in JAMA Network Open. Michael Silverstein, M.D., from the Boston Medical...
https://ift.tt/2Nro2kO
Alternative Payment Models Should Include Precision Medicine
TUESDAY, July 17, 2018 -- The American Medical Association has committed to working to integrate precision medicine into alternative payment models (APMs), according to an article published in the association's AMA Wire. Implementation of the...
https://ift.tt/2O05eKj
FDA: Some Rx Drugs May Become Available Without Seeing a Doctor
TUESDAY, July 17, 2018 -- A new draft guideline from the U.S. Food and Drug Administration suggests Americans could get widely used prescription medicines for cholesterol, high blood pressure, asthma, and migraine headaches without having to see a...
https://ift.tt/2Nro1gK
Roles of human epidermal growth factor receptor family in pulmonary lymphangioleiomyomatosis
Lymphangioleiomyomatosis (LAM) is a rare and refractory disease that affects women of reproductive age. Several target therapies are used to manage LAM but no curative modes of treatment have been reported yet. Therefore, in this study, we focused on targeting human epidermal growth factor receptor (HER) family proteins as a treatment strategy for LAM. In antibody array analysis, HER signaling was detected in the proteins extracted from LAM tissues. We then evaluated the expression of HER family members in 34 pulmonary LAM specimens using both immunohistochemistry and quantitative reverse transcription polymerase chain reaction (qRT-PCR).
https://ift.tt/2uvaspa
Tumor-infiltrating lymphocytes associate with outcome in non-endemic nasopharyngeal carcinoma: a multicenter study
The prognostic significance of tumor-infiltrating lymphocytes (TILs) has been studied recently in many cancers. For the first time in a non-endemic region, we have evaluated the prognostic value of TILs in a whole population-based nationwide cohort of nasopharyngeal carcinoma (NPC) in Finland. A total of 115 cases from Finnish hospitals were included. TILs were analyzed using hematoxylin and eosin stained slides according to the criteria of the International Immuno-Oncology Biomarker Working Group.
https://ift.tt/2zJuMIF
Predicting Enrollment in Multidisciplinary Clinical Care for Pediatric Weight Management
To characterize the children who were referred, determine the proportion of referred children who enrolled, and examine factors associated with enrollment in multidisciplinary clinical care for pediatric weight management.
https://ift.tt/2LeIlUR
Moving beyond race and ethnicity to understand the effect of inhaled nitric oxide on bronchopulmonary dysplasia prevention
We read with interest the report by Askie et al.1 If a patient's genetic profile could be used to predict favorable responses to specific interventions, potential resulting benefits would include improved outcomes, lower costs, and decreased risk of unwanted side effects of unnecessary interventions. The authors conclude that "[inhaled nitric oxide] iNO therapy should be considered for preterm African American infants at high risk for [bronchopulmonary dysplasia] BPD. iNO to prevent BPD in African Americans may represent an example of a racially customized therapy for infants."1 We respectfully disagree; we do not believe this recommendation advances the goals of personalized medicine and targeted interventions, and feel it may lead to unintended consequences.
https://ift.tt/2uH81iJ
Diuretics in newborns born extremely premature: the jury is still out
In their study, Blaisdell et al conclude that diuretics do not "substantially improve the respiratory status of the infant born extremely premature."1 I disagree with this interpretation. The main outcome measure of the study was "change in the respiratory status," defined on the basis of 5 very broad categories ("deceased," "endotracheal tube," "continuous positive airway pressure or nasal cannula >2 liters per minute," "nasal cannula <2 LPM," and "no support"; their Table II) that are not sensitive enough to detect the incremental improvement that may result from the use of diuretics.
https://ift.tt/2JvF6ng
The Role of Gender in Publication in The Journal of Pediatrics 2015-2016: Equal Reviews, Unequal Opportunities
To examine whether the gender of corresponding authors, reviewers, and editors led to differential publication recommendations and outcomes for original research articles and invited editorials submitted to The Journal of Pediatrics in 2015 and 2016.
https://ift.tt/2Lle9aE
National Trends in Hospitalization for Fever and Neutropenia in Children with Cancer, 2007-2014
To assess the trends of inpatient resource use and mortality in pediatric hospitalizations for fever with neutropenia in the US from 2007 to 2014.
https://ift.tt/2LeIoQx
Constipation Burden in Children with Autism Spectrum Disorder: Emergency Department and Healthcare Use
Autism spectrum disorder (ASD) is associated with high rates of gastrointestinal (GI) disturbances and comorbidities. The reported prevalence of GI symptoms in children with ASD varies greatly, which reflects methodologic limitations; however, constipation is consistently among the most frequently reported GI symptoms, with a prevalence of up to 50% or more, and has a meaningful impact on children with ASD and their families.1-4 Difficulties in acquiring bowel training, behavioral stool withholding, inadequate fluid intake, low fiber consumption, decreased activity, and medications resulting in altered GI and specifically decreased colonic motility have been cited as potential etiologies of constipation of children with ASD.
https://ift.tt/2uKBwQC
Intestinal Involvement in Kawasaki Disease
To describe a case of Kawasaki disease with intestinal involvement and to analyze other published reports to define clinical characteristics, diagnostic issues, and therapeutic approaches of gastrointestinal involvement in Kawasaki disease.
https://ift.tt/2LefOit
The Complexities of Ascertaining Public Preferences for Newborn Screening Policies
In this volume of The Journal, Tarini et al describe an online national survey of the public (n = 502) to evaluate preferences for attributes of candidate newborn screening (NBS) conditions.1 Using best–worst scaling, a preference measurement method from marketing economics,2 they found that, whether recommending or opposing screening, respondents indicated the cost of screening as the most important attribute. Respondents who recommended screening also considered important the number of babies diagnosed and judged as less important the age when symptoms start, success of treatment, and whether earlier knowledge of disease affects success of treatment.
https://ift.tt/2uJw1BN
Clinical Characteristics and Risk Factors for Developing Pulmonary Hypertension in Children with Down Syndrome
To determine the incidence, characteristics of, and risk factors contributing to the development of pulmonary hypertension in children with Down syndrome.
https://ift.tt/2LeIiIF
Can Real World Evidence on Body Mass Index Trajectories Inform Clinical Practice?
The incidence of pediatric obesity continues to increase worldwide and is a well-recognized public health crisis.1 Obesity is strongly associated with type 2 diabetes, but historically not with type 1 diabetes (T1D). However, autoimmune diabetes does not provide protection against the modern obesogenic environment, and in fact, aspects of T1D management, including treatment of hypoglycemia and dietary counseling, may contribute to unwanted weight gain.2
https://ift.tt/2uH4wZC
Appropriateness in prescribing PPIs: a position paper of the Italian Society of Gastroenterology (SIGE) − Study Section “Digestive Diseases in Primary Care”
The introduction of proton pump inhibitors (PPIs) into clinical practice about thirty years ago has greatly improved our therapeutic approach to acid-related diseases for their well-recognized efficacy and safety.Despite the well-defined indications, however, the use of PPIs continues to grow every year in both western and eastern countries and this phenomenon poses serious queries that include the onset of potential adverse effects and the increase in health care costs. The major reason explaining this worrying market expansion is the inappropriate use of PPIs.
https://ift.tt/2mnjobT
Diabetes is associated with advanced fibrosis and fibrosis progression in non-genotype 3 chronic hepatitis C patients
Diabetes is a risk factor of fibrosis progression in chronic hepatitis C (CHC). However, only one longitudinal study exploring whether diabetes is associated with progression from non-cirrhotic liver to cirrhosis in CHC patients has been conducted.
https://ift.tt/2uG8Los
Self-tracking of Physical Activity in People With Type 2 Diabetes: A Randomized Controlled Trial
https://ift.tt/2L1W2au
Immunoglobulin-induced aseptic meningitis: a case report
Immunoglobulin associated meningitis is a rare disease that mimics infectious meningitis. This is, to our knowledge, the first case of Immunoglobulin-associated meningitis described in a patient with Systemic ...
https://ift.tt/2LiXCUD
Psychometric Properties of the Canadian Nurse Informatics Competency Assessment Scale
https://ift.tt/2L3spWb
Automated Deterioration Detection Using Electronic Medical Record Data in Intensive Care Unit Patients: A Systematic Review
https://ift.tt/2LqbB7U
Development of the Canadian Nurse Informatics Competency Assessment Scale and Evaluation of Alberta's Registered Nurses' Self-perceived Informatics Competencies
https://ift.tt/2L4hhIU
Impact of Adoption of a Comprehensive Electronic Health Record on Nursing Work and Caring Efficacy
https://ift.tt/2JwtVdO
Prevalence of human anelloviruses in Romanian healthy subjects and patients with common pathologies
Human anelloviruses (TTV, TTMDV and TTMV) are at high prevalence all across the globe, having also a controversial disease-inducing potential. This study aimed to estimate the prevalence of anelloviral DNA in ...
https://ift.tt/2NVbxit
Epidemiological characterization of respiratory tract infections caused by Mycoplasma pneumoniae during epidemic and post-epidemic periods in North China, from 2011 to 2016
Mycoplasma pneumoniae (M. pneumoniae) is a commonly causative pathogen for respiratory tract infections (RTIs) in humans. The epidemiological features of M. pneumoniae infections during post-epidemic, including a...
https://ift.tt/2Np5rFN
‘Being able to bear a child’: Insights from Zimbabwean women in Melbourne
Publication date: Available online 17 July 2018
Source: Women and Birth
Author(s): Pranee Liamputtong, Sandra Benza
Abstract
Problem
In non-Western societies, childlessness carries numerous social consequences and has a significant impact on the gender identity and well-being of the women.
Background
The desire of women in non-Western societies is governed by numerous socio-cultural expectations including social norms and their own social position. At present, little is known about how Zimbabwean migrant women living in Australia perceive and experience childlessness and motherhood.
Aim
To discuss how children are seen in Zimbabwean culture and examine the personal and social ramification of infertility and cultural expectations of motherhood among Zimbabwean migrant women living in Australia. The perspectives and experiences of this migrant community are crucial so that we can avoid misunderstanding about the essence of motherhood among Zimbabwean women. This will ultimately lead to sensitive and culturally appropriate health and social care for migrants in a multicultural society of Australia.
Methods
The study is situated within the constructivist paradigm. Qualitative methods (in-depth interviewing, drawings and photo elicitation) were conducted with 15 Zimbabwean women. Data were analysed using thematic analysis method.
Findings
Being able to bear a child in Zimbabwean culture had a significant meaning to the women. Not only children could ensure the continuity of the society, having children was a form of social security as parents would be cared for by their children in old age. Childlessness threatens the social position of a woman and carries social consequences which significantly impact on their gender identity and well-being. Cultural expectations of motherhood placed the sole responsibility of caring for the children emotionally and physically on the mother.
Conclusion
The procreative value has not diminished despite having settled in Australia. An increased awareness of procreative needs for Zimbabwean women in a culturally and sensitive manner would enhance the emotional well-being of these women.
https://ift.tt/2muQFCd
Midwives’ personal use of complementary and alternative medicine (CAM) influences their recommendations to women experiencing a post-date pregnancy
Publication date: Available online 17 July 2018
Source: Women and Birth
Author(s): Lyndall Mollart, Virginia Skinner, Jon Adams, Maralyn Foureur
https://ift.tt/2uHEHZw
Process evaluation of the midwifery initiated oral health-dental service program: Perceptions of midwives in Greater Western Sydney, Australia
Publication date: Available online 17 July 2018
Source: Women and Birth
Author(s): Hannah G. Dahlen, Maree Johnson, Julia Hoolsema, Tiffany Patterson Norrie, Shilpi Ajwani, Anthony Blinkhorn, Sameer Bhole, Sharon Ellis, Ravi Srinivas, Albert Yaacoub, Andrew Milat, John Skinner, Ajesh George
Abstract
Background
Despite links between poor maternal oral health, adverse pregnancy outcomes and early childhood decay there is limited emphasis on maternal oral health in Australia. To address this, the Midwifery Initiated Oral Health Dental Service (MIOH-DS) program was developed in collaboration with the Australian College of Midwives.
Aims
To undertake a process evaluation and explore perceptions of midwives involved in the MIOH-DS program to determine its practicability, acceptability and feasibility if it were to be up-scaled and implemented into clinical practice.
Methods
Qualitative content analysis was undertaken on data from three focus groups with 21 midwives.
Findings
Midwives generally found the MIOH-DS to be acceptable and feasible with potential for widespread scalability. The trust women had in midwives was an important factor in gaining women's attention about oral health in pregnancy. The program assisted in increasing midwives' knowledge and awareness, though some felt it was outside their scope of practice. The oral health assessment tool was acceptable to midwives but some concerns were expressed about undertaking a visual oral inspection. Most midwives stated they were now confident with referring individuals to a dentist. Significant barriers to widespread implementation included the cost of dental care and the continued lack of awareness and misconceptions pregnant women had towards oral health.
Conclusion
Midwives found the MIOH-DS to be acceptable and feasible which are two important barriers to potential implementation at scale. Misconceptions over the importance of oral health by women and cost of accessing dental services still need resolving.
https://ift.tt/2msnf7n
Maternal, prenatal and traditional practice factors associated with perinatal mortality in Yemen
Publication date: Available online 17 July 2018
Source: Women and Birth
Author(s): Ahmed H. Al-Shahethi, Rafdzah Ahmad Zaki, Abdul Wahed A. Al-Serouri, Awang Bulgiba
Abstract
Background
Perinatal mortality remains a major international problem responsible for nearly six million stillbirths and neonatal deaths.
Objectives
To estimate the perinatal mortality rate in Sana'a, Yemen and to identify risk factors for perinatal deaths.
Methods
A community-based prospective cohort study was carried out between 2015 and 2016. Nine-hundred and eighty pregnant women were identified and followed up to 7 days following birth. A multi-stage cluster sampling was used to select participants from community households', residing in the five districts of the Sana'a City, Yemen.
Results
Total of 952 pregnant women were tracked up to 7 days after giving birth. The perinatal mortality rate, the stillbirth rate and the early neonatal mortality rate, were 89.3 per 1000, 46.2 per 1000 and 45.2 per 1000, respectively. In multivariable analysis older age (35+ years) of mothers at birth (Relative Risk = 2.83), teenage mothers' age at first pregnancy (<18 years) (Relative Risk = 1.57), primipara mothers (Relative Risk = 1.90), multi-nuclear family (Relative Risk = 1.74), mud house (Relative Risk = 2.02), mothers who underwent female genital mutilation (Relative Risk = 2.92) and mothers who chewed khat (Relative Risk = 1.60) were factors associated with increased risk of perinatal death, whereas a positive mother's tetanus vaccination status (Relative Risk = 0.49) were significant protective factors against perinatal deaths.
Conclusion
Rates of perinatal mortality were higher in Sana'a City compared to perinatal mortality at the national level estimated by World Health Organization. It is imperative there be sustainable interventions in order to improve the country's maternal and newborn health.
https://ift.tt/2uGXQux
A multi-layered poroelastic slab model under cyclic loading for a single osteon
An osteon consists of a multi-layered bone matrix and interstitial fluid flow in the lacunar–canalicular system. Loading-induced interstitial fluid flow in the lacunar–canalicular system is critical for osteoc...
https://ift.tt/2NV5VVr
Neisseria Gonorrhoae and their antimicrobial susceptibility patterns among symptomatic patients from Gondar town, north West Ethiopia
Neisseria gonorrhoeae, the causative agent of gonorrhoea, is a Gram negative, coffee-bean shaped facultative intracellular diplococcus bacterium, the classical sexually transmitted bacteria. Nowadays, N. gonorrho...
https://ift.tt/2NUGLGa
Collateral damage of using colistin in hospitalized patients on emergence of colistin-resistant Escherichia coli and Klebsiella pneumoniae colonization and infection
Colistin has been used for therapy of carbapenem-resistant Gram-negative infections in Thailand, especially carbapenem-resistant A. baumannii and P. aeruginosa, for more than 10 years. However, the prevalence of ...
https://ift.tt/2NoYJ2z
Calibration-free In Vitro Quantification of Protein Homo-oligomerization Using Commercial Instrumentation and Free, Open Source Brightness Analysis Software
https://ift.tt/2LgDvqk
The Identification of Sea Lamprey Pheromones Using Bioassay-Guided Fractionation
https://ift.tt/2zOfUZt
Visualizing the Interaction Between the Qdot-labeled Protein and Site-specifically Modified λ DNA at the Single Molecule Level
Here, we present a protocol to study DNA-protein interactions by total internal reflection fluorescence microscopy (TIRFM) using a site-specifically modified λ DNA substrate and a Quantum-dot labeled protein.
https://ift.tt/2uu0Cnt
Isolation, Expansion, and Adipogenic Induction of CD34+CD31+ Endothelial Cells from Human Omental and Subcutaneous Adipose Tissue
https://ift.tt/2mo7b6I
Visualization of DNA Compaction in Cyanobacteria by High-voltage Cryo-electron Tomography
https://ift.tt/2zMxahT
Cataract Surgery May Cut Risk of Serious Car Accidents
TUESDAY, July 17, 2018 -- Cataract surgery is associated with a modest decrease in the risk of the patient being in a serious traffic crash as the driver, according to a study published online June 28 in JAMA Ophthalmology. Matthew B. Schlenker,...
https://ift.tt/2L1sium
FDA Establishes New Task Force on Drug Shortages
TUESDAY, July 17, 2018 -- In a recent statement, U.S. Food and Drug Administration Commissioner Scott Gottlieb, M.D., announced the formation of a new drug shortages task force to thoroughly explore the reasons why drug shortages remain a persistent...
https://ift.tt/2KZurXz
Shared Decision-Making Approach to Zika Best for Travelers
TUESDAY, July 17, 2018 -- An approach to shared decision-making that stratifies risk might be most appropriate for preventing Zika infection, according to an Ideas and Opinion piece published online July 17 in the Annals of Internal Medicine. Noting...
https://ift.tt/2LrDs7V
Brief Safety Plan Intervention in ER Can Cut Suicidal Behavior
TUESDAY, July 17, 2018 -- Use of the Safety Planning Intervention (SPI) plus follow-up phone calls for suicidal patients presenting in the emergency department cuts suicidal behavior and increases the likelihood of outpatient mental health treatment...
https://ift.tt/2Jx1Inj
Immediate Monitoring With ECG Patch Ups A-Fib Diagnosis Rate
TUESDAY, July 17, 2018 -- Immediate monitoring with a self-applied wearable electrocardiogram (ECG) patch results in a higher rate of atrial fibrillation (AF) diagnosis among individuals at high risk, according to a study published in the July 10...
https://ift.tt/2L1sfyG
Preoperative Opioids Used by 23.1 Percent of Surgical Patients
TUESDAY, July 17, 2018 -- Preoperative opioid use is reported in 23.1 percent of patients undergoing surgery, according to a study published online July 11 in JAMA Surgery. Paul E. Hilliard, M.D., from the University of Michigan Health System in Ann...
https://ift.tt/2JB678Y
Evidence of Clinical Inertia in Management of T2DM
TUESDAY, July 17, 2018 -- Many patients with type 2 diabetes (T2D) who have a hemoglobin A1c (HbA1c) level expected to trigger treatment intensification often have treatment inappropriately delayed, according to a research letter published in the...
https://ift.tt/2L1seuC
Most Adults Perceive Nicotine Exposure As Harmful for Children
TUESDAY, July 17, 2018 -- Most adults perceive nicotine exposure as harmful for children; however, there are differences in perceptions based on sex, racial and/or ethnic background, and tobacco use, according to a study published online July 16 in...
https://ift.tt/2Lr9YHl
Higher Risk of In-Situ Breast CA, Ovarian Tumors With Fertility Tx
TUESDAY, July 17, 2018 -- For women undergoing assisted reproduction, there is no increased risk of corpus uteri or invasive breast cancer, but there is an increased risk of ovarian cancer and in situ breast cancer, according to a study published...
https://ift.tt/2L1scTw
Multiple Factors to Consider When Selecting NSAID for Arthritis
TUESDAY, July 17, 2018 -- Factors to be considered when choosing the correct nonsteroidal anti-inflammatory drug (NSAID) for arthritis include effectiveness, concurrent health conditions, and frequency of use, according to a blog post published by...
https://ift.tt/2JvcNW7
Study Links Children’s Eye-Hand Coordination with Their Academic Performance
New research findings show that young children with better eye-to-hand coordination scored higher on basic academic skills compared to their less-dexterous peers. The results, published in Psychological Science, signal an important relationship between children's ability to physically interact with their environment and their cognitive development
The study involved more than 300 primary school children in Bradford, West Yorkshire, in the United Kingdom. Experimenters under the supervision of Mark Mon-Williams, Professor of Cognitive Psychology at the University of Leeds, had the children, who ranged in age from 4 to 11, take part in computer tasks to measure their coordination and interceptive timing (their ability to interact with a moving object).
The tasks that measured eye-to-hand coordination involved steering, taking aim, and tracking objects on a computer screen.
In the 'interceptive timing' task, the children had to hit a moving object with an on-screen bat. This task taps into the brain's capacity for predicting the movement of objects through time and space, which is a fundamental cognitive ability.
After controlling for age, the researchers found that the children who performed better at the eye-to-hand coordination tasks tended to have higher achievement scores in reading, writing, and mathematics, based on national academic standards. Those who performed best at the 'steering task', in particular, averaged 9 months ahead of classmates who struggled with that eye-to-hand measurement.
While the children's interceptive timing skills tended to predict their attainment in math, it had no influence on reading and writing development, the researchers found.
The study doesn't demonstrate a direct cause and effect, but identifies a significant association between the ability to process physical surroundings and events and educational attainment, the authors say. This research builds on recent scientific findings suggesting that the ability of babies between the ages of 6 months and 13 months to understand the world around them affects their ability to manipulate numbers when they reach age 4.
"The current thinking among psychologists is that the neural circuitry used to build up a child's understanding of their external environment, the way they orientate themselves spatially and understand their world, is also used to process numbers and more abstract thinking,´ Mon-Williams says. "It also raises the question: should schools be identifying those children who are seen as clumsy or not so well coordinated and giving them extra support?
Lilycroft Primary School, the Bradford school where the study was conducted, is applying the findings. The school has remodeled its reception, indoor, and outdoor areas to include a space where children can develop their motor skills and their ability to call on large muscle groups to coordinate movement.
The research was funded by the Medical Research Council and the Economic and Social Research Council. It was conducted as part of the Born in Bradford project, a large study examining the health and well-being of 13,500 children born in the city, which has high rates of poverty and childhood illness.
https://ift.tt/2mq1hlq
Detection of Mitochondria Membrane Potential to Study CLIC4 Knockdown-induced HN4 Cell Apoptosis In Vitro
Here we present a detailed protocol for the application of rhodamine 123 to identify the mitochondrial membrane potential (MMP) and study CLIC4 knockdown-induced HN4 cell apoptosis in vitro. Under common fluorescence microscope and confocal laser scanning fluorescence microscope, the real-time change of the MMP was recorded.
https://ift.tt/2JvK4Ai
PIM1 overexpression in T-cell lymphomas protects tumor cells from apoptosis and confers doxorubicin resistance by upregulating c-myc expression
https://ift.tt/2NWftiU
Proton pump inhibitors increase the risk of cholecystitis: a population-based case-control study
We read with great interest the article by Cheung et al1 reporting long-term exposure to proton pump inhibitors (PPIs) following Helicobacter pylori (HP) eradication associated with increased risk of gastric cancer. PPIs are widely used worldwide to treat gastro-oesophageal reflux disorder, peptic ulcer and HP, but multiple reports have found they got some negative effects, such as increasing risk of the intra-abdominal infection, like spontaneous bacterial peritonitis,2 pseudomembranous colitis,3 liver abscess4 and affecting the gut microbiome.5 6 PPIs may theoretically increase risk of gaining acute cholecystitis due to the increasing the number of enteric organisms and risk of secondary infection; however, few reports have supported this hypothesis. Thus, we conducted a nationwide population-based case–control study to analyse the relationship between PPI exposure and incidence rate of cholecystitis.
We use the National Health Insurance Research Database in Taiwan of 2002–2011...
https://ift.tt/2L5QWtO
NAEMSP applauds formation of FDA drug shortages task force
WASHINGTON, D.C. — The National Association of EMS Physicians (NAEMSP) applauds the Food and Drug Administration's (FDA) formation of a Drug Shortages Task Force, which was created at the urging of Congress, NAEMSP and other medical groups representing physicians and medical professionals throughout the U.S. NAEMSP - an organization of more than 1,500 physicians and EMS professionals...
https://ift.tt/2NYWtjF
Ethnobotanical Study of Medicinal Plants Used to Treat Human Diseases in Berbere District, Bale Zone of Oromia Regional State, South East Ethiopia
This paper reports an ethnobotanical study that focused on the traditional medicinal plants used by local communities to treat human diseases. Ethnobotanical study of medicinal plants was carried out from June 25 to September 5, 2015, in Berbere district of Oromia region, Ethiopia. The study focused on documentation of medicinal plants used to treat various human diseases in the study area. Ethnobotanical data were collected using semistructured interviews, group discussion, guided field walks, and observations with participants. Preference ranking, paired comparison, direct matrix ranking, and informant consensus factors (ICF) were used to analyze the importance of some plant species. A total of 70 medicinal plants, distributed in 56 genera and 46 families, were collected and identified. Plant family with the highest medicinal plants in the study area used for various diseases treatment was Euphorbiaceae (11.4%). The result of growth form analysis showed that shrubs constituted the highest proportion of medicinal plants (48.6%). Roots, 43 (44.8%), were the most frequently utilized plant parts for preparation of traditional herbal medicines. Crushing was a widely used mode of preparation of traditional remedies where oral administration (37.5%) was the dominant route. The highest informants consensus factor (ICF) values were linked to gonorrhea and syphilis disease (0.95); the lowest was linked with external parasites and wound (0.69). Local people in the study area possess traditional knowledge of medicinal plants to treat various human ailments; however, agricultural expansion and disinterest of young generation became the major threat to medicinal plants. It is, therefore, necessary to preserve this indigenous knowledge on traditional medicines by proper documentation, identification of plant species used, and herbal preparation. To save medicinal plants from further loss, involving local communities in cultivation of the most utilized medicinal plants is recommended.
https://ift.tt/2KZpPk2
How to deal with two-year molars
Teething can be a difficult process for infants, toddlers, and caregivers. Two-year molars are the large teeth at the back of the mouth, and when they come in, it can cause even more discomfort and irritability. In this article, learn how to relieve related pain and which medications to avoid.
https://ift.tt/2LgocxO
Frontmatter
Journal Name: Biological Chemistry
Volume: 399
Issue: 8
Pages: i-iv
https://ift.tt/2NYWaFx
Exploratory cell dynamics: a sense of touch for cells?
Journal Name: Biological Chemistry
Volume: 399
Issue: 8
Pages: 809-819
https://ift.tt/2Npxi8H
Sphingolipid metabolism – an ambiguous regulator of autophagy in the brain
Journal Name: Biological Chemistry
Volume: 399
Issue: 8
Pages: 837-850
https://ift.tt/2NYl1JR
Insulin-like signaling within and beyond metazoans
Journal Name: Biological Chemistry
Volume: 399
Issue: 8
Pages: 851-857
https://ift.tt/2Np59yJ
Novel approach to quorum quenching: rational design of antibacterials in combination with hexahistidine-tagged organophosphorus hydrolase
Journal Name: Biological Chemistry
Volume: 399
Issue: 8
Pages: 869-879
https://ift.tt/2NY28Xs
New clues into the self-assembly of Vmh2, a basidiomycota class I hydrophobin
Journal Name: Biological Chemistry
Volume: 399
Issue: 8
Pages: 895-901
https://ift.tt/2JvspbS
Model construction of Niemann-Pick type C disease in zebrafish
Journal Name: Biological Chemistry
Volume: 399
Issue: 8
Pages: 903-910
https://ift.tt/2NU0YvP
Upregulation of Twist is involved in Gli1 induced migration and invasion of hepatocarcinoma cells
Journal Name: Biological Chemistry
Volume: 399
Issue: 8
Pages: 911-919
https://ift.tt/2Jvqvbk
Risks in Surrogacy Considering the Embryo: From the Preimplantation to the Gestational and Neonatal Period
Surrogacy is an assisted reproduction-based approach in which the intended parents assign the gestation and birth to another woman called the surrogate mother. The drivers of surrogacy refer largely to infertility, medical conditions, same-sex couples' parenting, and cases of diversity regarding sexual identity and orientation. Surrogacy consists of a valid option for a variety of conditions or circumstances ranging from medical to social reasons. However, surrogacy may be associated with risks during the preimplantation, prenatal, and neonatal period. It became obvious during the exhaustive literature research that data on surrogacy and its association with factors specific to the IVF practice and the options available were not fully represented. Could it be that surrogacy management adds another level of complexity to the process from the ovarian stimulation, the subsequent IVF cycle, and the techniques employed within the IVF and the Genetic Laboratory to the fetal, perinatal, and neonatal period? This work emphasizes the risks associated with surrogacy with respect to the preimplantation embryo, the fetus, and the infant. Moreover, it further calls for larger studies reporting on surrogacy and comparing the surrogate management to that of the routine IVF patient in order to avoid suboptimal management of a surrogate cycle. This is of particular importance in light of the fact that the surrogate cycle may include not only the surrogate but also the egg donor, sperm donor, and the commissioning couple or single person.
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Getting leaves into shape: a molecular, cellular, environmental and evolutionary view [REVIEW]
Leaves arise from groups of undifferentiated cells as small primordia that go through overlapping phases of morphogenesis, growth and differentiation. These phases are genetically controlled and modulated by environmental cues to generate a stereotyped, yet plastic, mature organ. Over the past couple of decades, studies have revealed that hormonal signals, transcription factors and miRNAs play major roles during leaf development, and more recent findings have highlighted the contribution of mechanical signals to leaf growth. In this Review, we discuss how modulating the activity of some of these regulators can generate diverse leaf shapes during development, in response to a varying environment, or between species during evolution.
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Gibberellins negatively modulate ovule number in plants [RESEARCH ARTICLE]
Ovule formation is a complex developmental process in plants, with a strong impact on the production of seeds. Ovule primordia initiation is controlled by a gene network, including components of the signaling pathways of auxin, brassinosteroids and cytokinins. By contrast, gibberellins (GAs) and DELLA proteins, the negative regulators of GA signaling, have never been shown to be involved in ovule initiation. Here, we provide molecular and genetic evidence that points to DELLA proteins as novel players in the determination of ovule number in Arabidopsis and in species of agronomic interest, such as tomato and rapeseed, adding a new layer of complexity to this important developmental process. DELLA activity correlates positively with ovule number, acting as a positive factor for ovule initiation. In addition, ectopic expression of a dominant DELLA in the placenta is sufficient to increase ovule number. The role of DELLA proteins in ovule number does not appear to be related to auxin transport or signaling in the ovule primordia. Possible crosstalk between DELLA proteins and the molecular and hormonal network controlling ovule initiation is also discussed.
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Bsx controls pineal complex development [RESEARCH ARTICLE]
Neuroendocrine cells in the pineal gland release melatonin during the night and, in teleosts, are directly photoreceptive. During development of the pineal complex, a small number of cells migrate leftward away from the pineal anlage to form the parapineal cell cluster, a process that is crucial for asymmetrical development of the bilateral habenular nuclei. Here, we show that, throughout zebrafish embryonic development, the brain-specific homeobox (bsx) gene is expressed in all cell types of the pineal complex. We identified Bmp and Noto/Flh as major regulators of bsx expression in the pineal complex. Upon loss of Bsx through the generation of a targeted mutation, embryos fail to form a parapineal organ and develop right-isomerized habenulae. Crucial enzymes in the melatonin biosynthesis pathway are not expressed, suggesting the absence of melatonin from the pineal gland in bsx mutants. Several genes involved in rod-like or cone-like phototransduction are also abnormally expressed, indicating that Bsx has a pivotal role in the differentiation of multiple cell types in the zebrafish pineal complex.
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Intracellular biosynthesis of lipids and cholesterol by Scap and Insig in mesenchymal cells regulates long bone growth and chondrocyte homeostasis [RESEARCH ARTICLE]
During enchondral ossification, mesenchymal cells express genes regulating the intracellular biosynthesis of cholesterol and lipids. Here, we have investigated conditional deletion of Scap or of Insig1 and Insig2 (Scap inhibits intracellular biosynthesis and Insig proteins activate intracellular biosynthesis). Mesenchymal condensation and chondrogenesis was disrupted in mice lacking Scap in mesenchymal progenitors, whereas mice lacking the Insig genes in mesenchymal progenitors had short limbs, but normal chondrogenesis. Mice lacking Scap in chondrocytes showed severe dwarfism, with ectopic hypertrophic cells, whereas deletion of Insig genes in chondrocytes caused a mild dwarfism and shortening of the hypertrophic zone. In vitro studies showed that intracellular cholesterol in chondrocytes can derive from exogenous and endogenous sources, but that exogenous sources cannot completely overcome the phenotypic effect of Scap deficiency. Genes encoding cholesterol biosynthetic proteins are regulated by Hedgehog (Hh) signaling, and Hh signaling is also regulated by intracellular cholesterol in chondrocytes, suggesting a feedback loop in chondrocyte differentiation. Precise regulation of intracellular biosynthesis is required for chondrocyte homeostasis and long bone growth, and these data support pharmacological modulation of cholesterol biosynthesis as a therapy for select cartilage pathologies.
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In locus analysis of patterning evolution of the BMP type II receptor Wishful thinking [RESEARCH ARTICLE]
Proper tissue patterning is an essential step during organ formation. During this process, genes are expressed in distinct patterns, defining boundaries for future functional domains. The bone morphogenetic protein (BMP) signaling pathway sets the anterior domain during eggshell patterning. Previously, the Drosophila melanogaster homolog of BMPR2, Wishful thinking (WIT), was shown to be required for BMP signaling and patterning during eggshell formation. Expressed in a conserved anterior pattern, the width of wit patterning in the follicular epithelium is evolutionarily divergent between Drosophila species. We used genome editing to demonstrate how the gene pattern divergence is controlled in cis within the wit locus of D. virilis. Furthermore, unlike direct targets of BMP signaling, we demonstrate how one transcription factor binding site shapes the pattern of WIT in D. melanogaster by negative regulation. However, changes in this site are not sufficient to explain the evolution of wit patterning, suggesting that a positive regulatory element that controls pattern divergence remains to be discovered.
https://ift.tt/2LoXBLK
TOR signaling in plants: conservation and innovation [PRIMER]
Target of rapamycin (TOR) is an evolutionarily conserved protein kinase that plays a central role in both plants and animals, despite their distinct developmental programs and survival strategies. Indeed, TOR integrates nutrient, energy, hormone, growth factor and environmental inputs to control proliferation, growth and metabolism in diverse multicellular organisms. Here, we compare the molecular composition, upstream regulators and downstream signaling relays of TOR complexes in plants and animals. We also explore and discuss the pivotal functions of TOR signaling in basic cellular processes, such as translation, cell division and stem/progenitor cell regulation during plant development.
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Single-cell biology: resolving biological complexity, one cell at a time [MEETING REVIEW]
In March 2018, over 250 researchers came together at the Wellcome Genome Campus in Hinxton, Cambridge, UK, to present their latest research in the area of single-cell biology. A highly interdisciplinary meeting, the Single Cell Biology conference covered a variety of topics, ranging from cutting-edge technological innovation, developmental biology and stem cell research to evolution and cancer. This meeting report summarises the key findings presented and the major research themes that emerged during the conference.
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Hedgehog-GLI signaling in Foxd1-positive stromal cells promotes murine nephrogenesis via TGF{beta} signaling [RESEARCH ARTICLE]
Normal kidney function depends on the proper development of the nephron: the functional unit of the kidney. Reciprocal signaling interactions between the stroma and nephron progenitor compartment have been proposed to control nephron development. Here, we show that removal of hedgehog intracellular effector smoothened (Smo-deficient mutants) in the cortical stroma results in an abnormal renal capsule, and an expanded nephron progenitor domain with an accompanying decrease in nephron number via a block in epithelialization. We show that stromal-hedgehog-Smo signaling acts through a GLI3 repressor. Whole-kidney RNA sequencing and analysis of FACS-isolated stromal cells identified impaired TGFβ2 signaling in Smo-deficient mutants. We show that neutralization and knockdown of TGFβ2 in explants inhibited nephrogenesis. In addition, we demonstrate that concurrent deletion of Tgfbr2 in stromal and nephrogenic cells in vivo results in decreased nephron formation and an expanded nephrogenic precursor domain similar to that observed in Smo-deficient mutant mice. Together, our data suggest a mechanism whereby a stromal hedgehog-TGFβ2 signaling axis acts to control nephrogenesis.
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Oncogenic cooperation between Yorkie and the conserved microRNA miR-8 in the wing disc of Drosophila [RESEARCH ARTICLE]
Tissue growth has to be carefully controlled to generate well-functioning organs. MicroRNAs are small non-coding RNAs that modulate the activity of target genes and play a pivotal role in animal development. Understanding the functions of microRNAs in development requires the identification of their target genes. Here, we find that miR-8, a conserved microRNA in the miR-200 family, controls tissue growth and homeostasis in the Drosophila wing imaginal disc. Upregulation of miR-8 causes the repression of Yorkie, the effector of the Hippo pathway in Drosophila, and reduces tissue size. Remarkably, co-expression of Yorkie and miR-8 causes the formation of neoplastic tumors. We show that upregulation of miR-8 represses the growth inhibitor brinker, and depletion of brinker cooperates with Yorkie in the formation of neoplastic tumors. Hence, miR-8 modulates a positive growth regulator, Yorkie, and a negative growth regulator, brinker. Deregulation of this network can result in the loss of tissue homeostasis and the formation of tumors.
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Sox30 initiates transcription of haploid genes during late meiosis and spermiogenesis in mouse testes [RESEARCH ARTICLE]
Transcription factors of the Sox protein family contain a DNA-binding HMG box and are key regulators of progenitor cell fate. Here, we report that expression of Sox30 is restricted to meiotic spermatocytes and postmeiotic haploids. Sox30 mutant males are sterile owing to spermiogenic arrest at the early round spermatid stage. Specifically, in the absence of Sox30, proacrosomic vesicles fail to form a single acrosomal organelle, and spermatids arrest at step 2-3. Although most Sox30 mutant spermatocytes progress through meiosis, accumulation of diplotene spermatocytes indicates a delayed or impaired transition from meiotic to postmeiotic stages. Transcriptome analysis of isolated stage-specific spermatogenic cells reveals that Sox30 controls a core postmeiotic gene expression program that initiates as early as the late meiotic cell stage. ChIP-seq analysis shows that Sox30 binds to specific DNA sequences in mouse testes, and its genomic occupancy correlates positively with expression of many postmeiotic genes including Tnp1, Hils1, Ccdc54 and Tsks. These results define Sox30 as a crucial transcription factor that controls the transition from a late meiotic to a postmeiotic gene expression program and subsequent round spermatid development.
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Two distinct ontogenies confer heterogeneity to mouse brain microglia [RESEARCH ARTICLE]
Hoxb8 mutant mice show compulsive behavior similar to trichotillomania, a human obsessive-compulsive-spectrum disorder. The only Hoxb8 lineage-labeled cells in the brains of mice are microglia, suggesting that defective Hoxb8 microglia caused the disorder. What is the source of the Hoxb8 microglia? It has been posited that all microglia progenitors arise at embryonic day (E) 7.5 during yolk sac hematopoiesis, and colonize the brain at E9.5. In contrast, we show the presence of two microglia subpopulations: canonical, non-Hoxb8 microglia and Hoxb8 microglia. Unlike non-Hoxb8 microglia, Hoxb8 microglia progenitors appear to be generated during the second wave of yolk sac hematopoiesis, then detected in the aorto-gonad-mesonephros (AGM) and fetal liver, where they are greatly expanded, prior to infiltrating the E12.5 brain. Further, we demonstrate that Hoxb8 hematopoietic progenitor cells taken from fetal liver are competent to give rise to microglia in vivo. Although the two microglial subpopulations are very similar molecularly, and in their response to brain injury and participation in synaptic pruning, they show distinct brain distributions which might contribute to pathological specificity. Non-Hoxb8 microglia significantly outnumber Hoxb8 microglia, but they cannot compensate for the loss of Hoxb8 function in Hoxb8 microglia, suggesting further crucial differences between the two subpopulations.
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Stratum recruits Rab8 at Golgi exit sites to regulate the basolateral sorting of Notch and Sanpodo [RESEARCH ARTICLE]
In Drosophila, the sensory organ precursor (SOP or pI cell) divides asymmetrically to give birth to daughter cells, the fates of which are governed by the differential activation of the Notch pathway. Proteolytic activation of Notch induced by ligand is based on the correct polarized sorting and localization of the Notch ligand Delta, the Notch receptor and its trafficking partner Sanpodo (Spdo). Here, we have identified Stratum (Strat), a presumptive guanine nucleotide exchange factor for Rab GTPases, as a regulator of Notch activation. Loss of Strat causes cell fate transformations associated with an accumulation of Notch, Delta and Spdo in the trans-Golgi network (TGN), and an apical accumulation of Spdo. The strat mutant phenotype is rescued by the catalytically active as well as the wild-type form of Rab8, suggesting a chaperone function for Strat rather than that of exchange factor. Strat is required to localize Rab8 at the TGN, and rab8 phenocopies strat. We propose that Strat and Rab8 act at the exit of the Golgi apparatus to regulate the sorting and the polarized distribution of Notch, Delta and Spdo.
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Defective endothelial cell migration in the absence of Cdc42 leads to capillary-venous malformations [RESEARCH ARTICLE]
Formation and homeostasis of the vascular system requires several coordinated cellular functions, but their precise interplay during development and their relative importance for vascular pathologies remain poorly understood. Here, we investigated the endothelial functions regulated by Cdc42 and their in vivo relevance during angiogenic sprouting and vascular morphogenesis in the postnatal mouse retina. We found that Cdc42 is required for endothelial tip cell selection, directed cell migration and filopodia formation, but dispensable for cell proliferation or apoptosis. Although the loss of Cdc42 seems generally compatible with apical-basal polarization and lumen formation in retinal blood vessels, it leads to defective endothelial axial polarization and to the formation of severe vascular malformations in capillaries and veins. Tracking of Cdc42-depleted endothelial cells in mosaic retinas suggests that these capillary-venous malformations arise as a consequence of defective cell migration, when endothelial cells that proliferate at normal rates are unable to re-distribute within the vascular network.
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Two independent sulfation processes regulate mouth-form plasticity in the nematode Pristionchus pacificus [RESEARCH ARTICLE]
Sulfation of biomolecules, like phosphorylation, is one of the most fundamental and ubiquitous biochemical modifications with important functions during detoxification. This process is reversible, involving two enzyme classes: a sulfotransferase, which adds a sulfo group to a substrate; and a sulfatase that removes the sulfo group. However, unlike phosphorylation, the role of sulfation in organismal development is poorly understood. In this study, we find that two independent sulfation events regulate the development of mouth morphology in the nematode Pristionchus pacificus. This nematode has the ability to form two alternative mouth morphologies depending on environmental cues, an example of phenotypic plasticity. We found that, in addition to a previously described sulfatase, a sulfotransferase is involved in regulating the mouth-form dimorphism in P. pacificus. However, it is unlikely that both of these sulfation-associated enzymes act upon the same substrates, as they are expressed in different cell types. Furthermore, animals mutant in genes encoding both enzymes show condition-dependent epistatic interactions. Thus, our study highlights the role of sulfation-associated enzymes in phenotypic plasticity of mouth structures in Pristionchus.
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An interview with Richard Gardner [SPOTLIGHT]
Richard Gardner began his career as a PhD student with Bob Edwards and ran his own lab, focusing on patterning of the early mammalian embryo, at the University of Oxford from 1973 until his retirement in 2008. A Fellow of the Royal Society since 1979, he was knighted for services to Biological Sciences in 2005 and received an Honorary Doctorate from Cambridge University in 2012. This year he was awarded the British Society of Developmental Biology (BSDB) Waddington Medal for major contributions to developmental biology in the UK. We caught up with him at the society's Spring Meeting in Warwick and discussed how a book of birds set him on a path to science, how his research was complemented by decades of advising government on scientific policy and why picking the right mentor in research is so important.
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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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heory of COVID-19 pathogenesis Publication date: November 2020Source: Medical Hypotheses, Volume 144Author(s): Yuichiro J. Suzuki ScienceD...
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