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Training in systems pharmacology: predoctoral program in pharmacology and systems biology at Mount Sinai School of Medicine.

ABSTRACT: Our recently developed predoctoral training program in pharmacology and systems biology prepares students to become experts in systems-level models of disease that identify therapeutic targets and predict adverse effects or new uses of existing therapeutics. Multiple computational modeling modes are introduced throughout a curriculum that integrates basic cell and molecular sciences with the physiology and pathophysiology of disease states. Problem-based learning exercises enable students from different experimental and computational backgrounds to design experiments and interpret data quantitatively.

SUBMITTER: Sobie EA

PROVIDER: S-EPMC3037798 | biostudies-literature | 2010 Jul

REPOSITORIES: biostudies-literature

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Training in systems pharmacology: predoctoral program in pharmacology and systems biology at Mount Sinai School of Medicine.

Sobie E A EA Jenkins S L SL Iyengar R R Krulwich T A TA

Clinical pharmacology and therapeutics 20100701 1

Our recently developed predoctoral training program in pharmacology and systems biology prepares students to become experts in systems-level models of disease that identify therapeutic targets and predict adverse effects or new uses of existing therapeutics. Multiple computational modeling modes are introduced throughout a curriculum that integrates basic cell and molecular sciences with the physiology and pathophysiology of disease states. Problem-based learning exercises enable students from d ...[more]

PMID: 20562890

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The COVID-19 Student WorkForce at the Icahn School of Medicine at Mount Sinai: A Model for Rapid Response in Emergency Preparedness.

Project description:ProblemIn accordance with guidelines from the Association of American Medical Colleges, medical schools across the United States suspended clerkships and transitioned preclinical courses online in March 2020 because of the COVID-19 pandemic. Hospitals and health systems faced significant burdens during this time, particularly in New York City.ApproachThird- and fourth-year medical students at the Icahn School of Medicine at Mount Sinai formed the COVID-19 Student WorkForce to connect students to essential roles in the Mount Sinai Hospital System and support physicians, staff members, researchers, and hospital operations. With the administration's support, the WorkForce grew to include over 530 medical and graduate students. A methodology was developed for clinical students to receive elective credit for these volunteer activities.OutcomesFrom March 15, 2020, to June 14, 2020, student volunteers recorded 29,602 hours (2,277 hours per week) in 7 different task forces, which operated at 7 different hospitals throughout the health system. Volunteers included students from all years of medical school as well as PhD, master's, and nursing students. The autonomous structure of the COVID-19 Student WorkForce was unique and contributed to its ability to quickly mobilize students to necessary tasks. The group leaders collaborated with other medical schools in the New York City area, sharing best practices and resources and consulting on a variety of topics.Next stepsGoing forward, the COVID-19 Student WorkForce will continue to collaborate with student leaders of other institutions and prevent volunteer burnout; transition select initiatives into structured, precepted student roles for clinical education; and maintain a state of readiness in the event of a second surge of COVID-19 infections in the New York City area.

| S-EPMC8140623 | biostudies-literature

The Mount Sinai Hospital Institute for critical care medicine response to the COVID-19 pandemic.

Project description:BackgroundThe coronavirus disease 2019 (COVID-19) pandemic resulted in a surge of critically ill patients. This was especially true in New York City. We present a roadmap for hospitals and healthcare systems to prepare for a Pandemic.MethodsThis was a retrospective review of how Mount Sinai Hospital (MSH) was able to rapidly prepare to handle the pandemic. MSH, the largest academic hospital within the Mount Sinai Health System, rapidly expanded the intensive care unit (ICU) bed capacity, including creating new ICU beds, expanded the workforce, and created guidelines.ResultsMSH a 1,139-bed quaternary care academic referral hospital with 104 ICU beds expanded to 1,453 beds (27.5% increase) with 235 ICU beds (126% increase) during the pandemic peak in the first week of April 2020. From March to June 2020, with follow-up through October 2020, MSH admitted 2,591 COVID-19-positive patients, 614 to ICUs. Most admitted patients received noninvasive support including a non-rebreather mask, high flow nasal cannula, and noninvasive positive pressure ventilation. Among ICU patients, 68.4% (n=420) received mechanical ventilation; among the admitted ICU patients, 42.8% (n=263) died, and 47.8% (n=294) were discharged alive.ConclusionsFlexible bed management initiatives; teamwork across multiple disciplines; and development and implementation of guidelines were critical accommodating the surge of critically ill patients. Non-ICU services and staff were deployed to augment the critical care work force and open new critical care units. This approach to rapidly expand bed availability and staffing across the system helped provide the best care for the patients and saved lives.

| S-EPMC8435441 | biostudies-literature

Pathophysiology of SARS-CoV-2: the Mount Sinai COVID-19 autopsy experience.

Project description:Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and its associated clinical syndrome COVID-19 are causing overwhelming morbidity and mortality around the globe and disproportionately affected New York City between March and May 2020. Here, we report on the first 100 COVID-19-positive autopsies performed at the Mount Sinai Hospital in New York City. Autopsies revealed large pulmonary emboli in six cases. Diffuse alveolar damage was present in over 90% of cases. We also report microthrombi in multiple organ systems including the brain, as well as hemophagocytosis. We additionally provide electron microscopic evidence of the presence of the virus in our samples. Laboratory results of our COVID-19 cohort disclose elevated inflammatory markers, abnormal coagulation values, and elevated cytokines IL-6, IL-8, and TNFα. Our autopsy series of COVID-19-positive patients reveals that this disease, often conceptualized as a primarily respiratory viral illness, has widespread effects in the body including hypercoagulability, a hyperinflammatory state, and endothelial dysfunction. Targeting of these multisystemic pathways could lead to new treatment avenues as well as combination therapies against SARS-CoV-2 infection.

| S-EPMC8015313 | biostudies-literature

Interconnected Microphysiological Systems for Quantitative Biology and Pharmacology Studies.

Project description:Microphysiological systems (MPSs) are in vitro models that capture facets of in vivo organ function through use of specialized culture microenvironments, including 3D matrices and microperfusion. Here, we report an approach to co-culture multiple different MPSs linked together physiologically on re-useable, open-system microfluidic platforms that are compatible with the quantitative study of a range of compounds, including lipophilic drugs. We describe three different platform designs - "4-way", "7-way", and "10-way" - each accommodating a mixing chamber and up to 4, 7, or 10 MPSs. Platforms accommodate multiple different MPS flow configurations, each with internal re-circulation to enhance molecular exchange, and feature on-board pneumatically-driven pumps with independently programmable flow rates to provide precise control over both intra- and inter-MPS flow partitioning and drug distribution. We first developed a 4-MPS system, showing accurate prediction of secreted liver protein distribution and 2-week maintenance of phenotypic markers. We then developed 7-MPS and 10-MPS platforms, demonstrating reliable, robust operation and maintenance of MPS phenotypic function for 3 weeks (7-way) and 4 weeks (10-way) of continuous interaction, as well as PK analysis of diclofenac metabolism. This study illustrates several generalizable design and operational principles for implementing multi-MPS "physiome-on-a-chip" approaches in drug discovery.

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Systems medicine: evolution of systems biology from bench to bedside.

Project description:High-throughput experimental techniques for generating genomes, transcriptomes, proteomes, metabolomes, and interactomes have provided unprecedented opportunities to interrogate biological systems and human diseases on a global level. Systems biology integrates the mass of heterogeneous high-throughput data and predictive computational modeling to understand biological functions as system-level properties. Most human diseases are biological states caused by multiple components of perturbed pathways and regulatory networks rather than individual failing components. Systems biology not only facilitates basic biological research but also provides new avenues through which to understand human diseases, identify diagnostic biomarkers, and develop disease treatments. At the same time, systems biology seeks to assist in drug discovery, drug optimization, drug combinations, and drug repositioning by investigating the molecular mechanisms of action of drugs at a system's level. Indeed, systems biology is evolving to systems medicine as a new discipline that aims to offer new approaches for addressing the diagnosis and treatment of major human diseases uniquely, effectively, and with personalized precision.

| S-EPMC4457580 | biostudies-literature

Early Life Characteristics and Neurodevelopmental Phenotypes in the Mount Sinai Children's Environmental Health Center.

Project description:Neurodevelopmental outcomes including behavior, executive functioning, and IQ exhibit complex correlational structures, although they are often treated as independent in etiologic studies. We performed a principal components analysis of the behavioral assessment system for children, the behavior rating inventory of executive functioning, and the Wechsler scales of intelligence in a prospective birth cohort, and estimated associations with early life characteristics. We identified seven factors: (1) impulsivity and externalizing, (2) executive functioning, (3) internalizing, (4) perceptual reasoning, (5) adaptability, (6) processing speed, and (7) verbal intelligence. Prenatal fish consumption, maternal education, preterm birth, and the home environment were important predictors of various neurodevelopmental factors. Although maternal smoking was associated with more adverse externalizing, executive functioning, and adaptive composite scores in our sample, of the orthogonally-rotated factors, smoking was only associated with the impulsivity and externalizing factor ([Formula: see text] - 0.82, 95% CI -?1.42, -?0.23). These differences may be due to correlations among outcomes that were accounted for by using a phenotypic approach. Dimension reduction may improve upon traditional approaches by accounting for correlations among neurodevelopmental traits.

| S-EPMC6432778 | biostudies-literature

Enabling Precision Cardiology Through Multiscale Biology and Systems Medicine.

Project description:The traditional paradigm of cardiovascular disease research derives insight from large-scale, broadly inclusive clinical studies of well-characterized pathologies. These insights are then put into practice according to standardized clinical guidelines. However, stagnation in the development of new cardiovascular therapies and variability in therapeutic response implies that this paradigm is insufficient for reducing the cardiovascular disease burden. In this state-of-the-art review, we examine 3 interconnected ideas we put forth as key concepts for enabling a transition to precision cardiology: 1) precision characterization of cardiovascular disease with machine learning methods; 2) the application of network models of disease to embrace disease complexity; and 3) using insights from the previous 2 ideas to enable pharmacology and polypharmacology systems for more precise drug-to-patient matching and patient-disease stratification. We conclude by exploring the challenges of applying a precision approach to cardiology, which arise from a deficit of the required resources and infrastructure, and emerging evidence for the clinical effectiveness of this nascent approach.

| S-EPMC6034501 | biostudies-literature

The Mount Sinai cohort of large-scale genomic, transcriptomic and proteomic data in Alzheimer's disease.

Project description:Alzheimer's disease (AD) affects half the US population over the age of 85 and is universally fatal following an average course of 10 years of progressive cognitive disability. Genetic and genome-wide association studies (GWAS) have identified about 33 risk factor genes for common, late-onset AD (LOAD), but these risk loci fail to account for the majority of affected cases and can neither provide clinically meaningful prediction of development of AD nor offer actionable mechanisms. This cohort study generated large-scale matched multi-Omics data in AD and control brains for exploring novel molecular underpinnings of AD. Specifically, we generated whole genome sequencing, whole exome sequencing, transcriptome sequencing and proteome profiling data from multiple regions of 364 postmortem control, mild cognitive impaired (MCI) and AD brains with rich clinical and pathophysiological data. All the data went through rigorous quality control. Both the raw and processed data are publicly available through the Synapse software platform.

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Emergency Medicine Physician Assistant (EMPA) Postgraduate Training Programs: Program Characteristics and Training Curricula.

Project description:A growing number of formal postgraduate training programs have been established to provide emergency medicine physician assistants (EMPA) with the unique skills and knowledge to work in the emergency department (ED). The objective of this study was to provide an overview of the current state of EMPA postgraduate training and to describe program characteristics and curriculum components.We conducted a cross-sectional study of EMPA postgraduate training programs using data from websites and contacting individual programs to provide program characteristics and curriculum components. Variables collected included length of program, curriculum (e.g., clinical rotations, didactic experience, and research opportunities), size of program/number of trainees, affiliation with emergency medicine (EM) residency, geographic location, and salary.We identified 29 EMPA postgraduate training programs in 17 states, with at least one additional program in development. The mean length of EMPA training programs is 15 months (range 12-24 months). The most common non-ED/elective rotations are orthopedics, ultrasound, anesthesiology, and trauma. The mean number of trainees per class is 3.46 (median 3, range 1-16 trainees); 27 of 29 (93%) programs were in institutions that also had an EM residency program. The mean annual salary is $58,566 (range $43,000-90,000).EMPA postgraduate training programs have common characteristics and curriculum components despite a lack of a specialty-specific accrediting organization or certifying examination. The overall growth and current number of these programs merits further research focusing on whether standardized curricula, formal recognition, and accreditation should be developed.

| S-EPMC6123089 | biostudies-other

Advancing Systems Biology in the International Conference on Intelligent Biology and Medicine (ICIBM) 2015.

Project description:The 2015 International Conference on Intelligent Biology and Medicine (ICIBM 2015) was held on November 13-15, 2015 in Indianapolis, Indiana, USA. ICIBM 2015 included eight scientific sessions, three tutorial sessions, one poster session, and four keynote presentations that covered the frontier research in broad areas related to bioinformatics, systems biology, big data science, biomedical informatics, pharmacogenomics, and intelligent computing. Here, we present a summary of the 10 research articles that were selected from ICIBM 2015 and included in the supplement to BMC Systems Biology.

| S-EPMC5009564 | biostudies-literature

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