Using induced pluripotent stem cells derived neurons to model brain diseases

The ability to use induced pluripotent stem cells（i PSC）to model brain diseases is a powerful tool for unraveling mechanistic alterations in these disorders.Rodent models of brain diseases have spurred understanding of pathology but the concern arises that they may not recapitulate the full spectrum of neuron disruptions associated with human neuropathology.iPSC derived neurons,or other neural cell types,provide the ability to access pathology in cells derived directly from a patient＇s blood sample or skin biopsy where availability of brain tissue is limiting.Thus,utilization of iPSC to study brain diseases provides an unlimited resource for disease modelling but may also be used for drug screening for effective therapies and may potentially be used to regenerate aged or damaged cells in the future.Many brain diseases across the spectrum of neurodevelopment,neurodegenerative and neuropsychiatric are being approached by iPSC models.The goal of an iPSC based disease model is to identify a cellular phenotype that discriminates the disease-bearing cells from the control cells.In this mini-review,the importance of iPSC cell models validated for pluripotency,germline competency and function assessments is discussed.Selected examples for the variety of brain diseases that are being approached by iPSC technology to discover or establish the molecular basis of the neuropathology are discussed.

A Brief Overview of How Male Medicine Co-Opted the Midwife’s Role in the Birth Process

The term medicalization has been defined as the process by which non-medical issues come to be defined and treated as medical problems. There are no better examples of this than pregnancy and childbirth. Prior to the intervention of physicians and hospitals, most females delivered unassisted or assisted by a relative or a midwife who usually had no formal education. As long as this remained the practice, pregnancy could not become a medical procedure. Through systematic changes, discussed in detail herein, this primarily female-oriented event involving family and amateur aids would come to be dominated by males who were the sole legally authorized providers of obstetrical care [1]. The increasing cultural authority of medicine facilitated the transfer of home delivery to hospital delivery and changed normal birth into a surgical procedure. This paper will examine the history of obstetrics and how a profession comes to redefine a normal life event as a disease state.

Weight Management of Young Women with Down Syndrome: <i>C-ICAN</i>Meal Plan

Primary care physicians are in a unique position to provide a holistic and individualized care to their patients with Down Syndrome. These patients share common medical problems with general population;however, they often are medically complex and present with cardiac, orthopedic, and endocrine challenges such as overweight-obesity and related comorbidities that occur with more frequency in this unique population. The prevention of overweight-obesity is an important public health issue for both the general population and for the population of individuals with Down Syndrome. If abnormal weight gain is treated early and effectively many secondary comorbidities can be prevented or ameliorated. This case report discusses the impact of implementing a Consistent Individualized Carbohydrate controlled Anti-inflammatory Nutrition plan (C-ICAN) as part of the treatment plan for a young woman with Down Syndrome (DS). The C-ICAN meal plan is a low glycemic load meal plan with 30% to 35% calories from fat, 20% to 25% calories from protein, 40% to 45% calories from carbohydrate, and goal of 25 gm fiber per day. The C-ICAN meal plan combines the Mediterranean diet because of its well-established anti-inflammatory, and cardiovascular benefits, with a high protein and low glycemic-load meal plan to improve satiety and glycemic control. In this case the patient and her caregivers adjusted to a structured meal pattern well, weight balance resulted, and mealtime stress was reduced.

How Silencing of Dissent in Science Impacts Woman.The Gardasil^(■)Story

The issues of safety and efficacy of certain vaccines remains extremely contentious. The venues for this debate have included periodicals, documentary films, and an ever-increasing number of on-line sites. While debate in science is not only a common occurrence but a fundamental tenet of the scientific community, it only works when divergent opinions can be heard. When those who hold an opposing opinion are denigrated and/or marginalized by those holding the majority opinion such as in the issue of vaccination, where cultural authority for the issue is owned by the profession of medicine, both science and the public lose. What is often forgotten are the benefits derived from the questioning of drug safety that not only extends to the public but to physicians who rely on the truthfulness and accuracy of the information that is being supplied to them by manufactures and government agencies. While most physicians believe they are functioning in their patient’s best interest when making vaccine recommendations, these recommendations by in large have become a matter of rote and are made because most physicians have bought into the “vaccines are safe” mantra. What most physicians don’t realize is they have unknowingly been recruited by big pharma to assist in shutting down the vaccination debate. This suppression of vaccine opposition even among academics, is becoming more commonplace and will lead down a slippery slope that will silence opposition science, and the dangers that come with this. Those who question vaccine safety have been ostracized, misquoted and even made to appear mentally ill by those who hold the majority opinion on the issue. Physicians who question vaccine safety have had their licenses threatened or have been fired from positions. Tactics such as name calling and the use of terms such as pseudo-science, (even when the evidence being presented is from widely accepted peer-reviewed journals) or “conspiracy theorists” which has the effect of placing those holding the minority opinion in the category of such groups as 9/11 truthers, are not uncommon. Other methods of curtailing the presentation of opposing vaccine views have included pressuring venues not to allow anti-vaccination proponents to appear, or using the media to “expose” anti-vaccination groups as “crack-pots” while simultaneously presenting the majority opinion and the presenters as the sole arbiters on the issue. The more extreme elements of the pro-vaccine group will even make the statement that the issue is settled and there is no need for discussion. “Has there ever been a society which has died of dissent? Several have died of conformity in our lifetime.” Jacob Bronowski in Science and Human

利用羊水量对分娩时进行评估的一项随机临床试验:羊水指数与单一最大羊水暗区检测技术比较

Objective The purpose of this study was to determine whether an intra partum as sessment of amniotic fluid identifies a pregnancy that is at risk for an adverse outcome. Study design Parturients who were admitted for delivery were assigned randomly to have the amniotic fluid assessed either by amniotic fluid index or b y the presence of a 2 ×1 pocket. Results The amniotic fluid index was obtained in 499 pregnancies, and the 2 ×1 technique was performed in 501. Oligohydramnio s was diagnosed in 25%of amniotic fluid index pregnancies versus 8%with the us e of the 2 ×1 pocket technique (P < .001). Both techniques failed to identify p atients who underwent an amnioinfusion for fetal distress (P=.864) or who experi enced variable (P=.208) or late decelerations (P=.210) that influenced delivery, fetal distress in labor (P=.220), caesarean delivery for fetal distress (P=.133 ), and admission to neonatal intensive care unit (P=.686). Conclusion Neither th e amniotic fluid index nor the 2 ×1 pocket technique that was undertaken as a f etal admission test identi fies a pregnancy that is at risk for an adverse outco me.

The impact of daylight and window views on length of stay among patients with heart disease:A retrospective study in a cardiac intensive care unit

Background:Heart disease is the leading cause of death in the United States.The length of stay(LOS)is a well-established parameter used to evaluate health outcomes among critically ill patients with heart disease in cardiac intensive care units(CICUs).While evidence suggests that the presence of daylight and window views can positively influence patients’LOS,no studies to date have differentiated the impact of daylight from window views on heart disease patients.Also,existing research studies on the impact of daylight and window views have failed to account for key clinical and demographic variables that can impact the benefit of such interventions in CICUs.Methods:This retrospective study investigated the impact of access to daylight vs.window views on CICU patients'LOS.The study CICU is located in a hospital in the southeast United States and has rooms of the same size with different types of access to daylight and window views,including rooms with daylight and window views(with the patient bed located parallel to full-height,south-facing windows),rooms with daylight and no window views(with the patient bed located perpendicular to the windows),and windowless rooms.Data from electronic health records(EHRs)for the time-period September 2015 to September 2019(n=2936)were analyzed to investigate the impact of room type on patients’CICU LOS.Linear regression models were developed for the outcome of interest,controlling for potential confounding variables.Results:Ultimately,2319 patients were finally included in the study analysis.Findings indicated that patients receiving mechanical ventilation in rooms with access to daylight and window views had shorter LOS durations(16.8 h)than those in windowless rooms.Sensitivity analysis for a subset of patients with LOS≤3 days revealed that parallel bed placement to the windows and providing access to both daylight and window views significantly reduced their LOS compared to windowless rooms in the unit(P=0.007).Also,parallel bed placement to the window significantly reduced LOS in this patient subset for those with an experience of delirium(P=0.019),dementia(P=0.008),anxiety history(P=0.009),obesity(P=0.003),and those receiving palliative care(P=0.006)or mechanical ventilation(P=0.033).Conclusions:Findings from this study could help architects make design decisions and determine optimal CICU room layouts.Identifying the patients who benefit most from direct access to daylight and window views may also help CICU stakeholders with patient assignments and hospital training programs.

Applying Big Data Based Deep Learning System to Intrusion Detection

With vast amounts of data being generated daily and the ever increasing interconnectivity of the world’s internet infrastructures,a machine learning based Intrusion Detection Systems(IDS)has become a vital component to protect our economic and national security.Previous shallow learning and deep learning strategies adopt the single learning model approach for intrusion detection.The single learning model approach may experience problems to understand increasingly complicated data distribution of intrusion patterns.Particularly,the single deep learning model may not be effective to capture unique patterns from intrusive attacks having a small number of samples.In order to further enhance the performance of machine learning based IDS,we propose the Big Data based Hierarchical Deep Learning System(BDHDLS).BDHDLS utilizes behavioral features and content features to understand both network traffic characteristics and information stored in the payload.Each deep learning model in the BDHDLS concentrates its efforts to learn the unique data distribution in one cluster.This strategy can increase the detection rate of intrusive attacks as compared to the previous single learning model approaches.Based on parallel training strategy and big data techniques,the model construction time of BDHDLS is reduced substantially when multiple machines are deployed.

PBNA: An Improved Probabilistic Biological Network Alignment Method

Biological network alignment is an important research topic in the field of bioinformatics. Nowadays almost every existing alignment method is designed to solve the deterministic biological network alignment problem.However, it is worth noting that interactions in biological networks, like many other processes in the biological realm,are probabilistic events. Therefore, more accurate and better results can be obtained if biological networks are characterized by probabilistic graphs. This probabilistic information, however, increases difficulties in analyzing networks and only few methods can handle the probabilistic information. Therefore, in this paper, an improved Probabilistic Biological Network Alignment（PBNA） is proposed. Based on Iso Rank, PBNA is able to use the probabilistic information. Furthermore, PBNA takes advantages of Contributor and Probability Generating Function（PGF） to improve the accuracy of node similarity value and reduce the computational complexity of random variables in similarity matrix. Experimental results on dataset of the Protein-Protein Interaction（PPI） networks provided by Todor demonstrate that PBNA can produce some alignment results that ignored by the deterministic methods, and produce more biologically meaningful alignment results than Iso Rank does in most of the cases based on the Gene Ontology Consistency（GOC） measure. Compared with Prob method, which is designed exactly to solve the probabilistic alignment problem, PBNA can obtain more biologically meaningful mappings in less time.

Autoimmune Hepatitis Induced after Treatment of Syphilitic Hepatitis

We present a unique case of biopsy-proven syphilitic hepa-titis which presented as severe acute liver injury with sig-nificant elevation in aminotransferases and bilirubin,and improved with antibiotic therapy.However,the patient re-turned weeks after initial presentation with new-onset acute liver injury and had developed hypergammaglobulinemia,positive autoantibody titers,and repeat liver biopsy dem-onstrating interface hepatitis,supporting a diagnosis of autoimmune hepatitis.He had an otherwise unrevealing etiologic workup,and responded to glucocorticoid therapy.We believe that syphilitic hepatitis and its treatment sub-sequently triggered an immunogenic response,leading to autoimmune hepatitis.Autoimmune hepatitis is a chronic liver disease thought to manifest as a result of predisposing genetic factors in combination with environmental insults,especially hepatotropic pathogens.Syphilis is a sexually transmitted disease caused by Treponema pallidum that has been associated with autoimmunity and the develop-ment of autoantibodies.We propose that in the setting of syphilitic hepatitis,a molecular mimicry event resulting from structural similarities between T.pallidum and liver antigens,as well as impaired regulatory T-cell function,led to the breakdown of immune tolerance and the onset of au-toimmune hepatitis.To support this hypothesis,further mo-lecular analyses and case series are necessary to determine if syphilitic hepatitis and its treatment are risk factors for the onset of autoimmune hepatitis.Autoimmune hepatitis should be considered early as the cause of acute liver injury in susceptible patients with risk factors for the disease,as prompt recognition and appropriate treatment may prevent progression of liver injury and result in improved outcomes.