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"Weiss, Yoram"
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Economics of the family
\"The family is a complex decision unit in which partners with potentially different objectives make consumption, work, and fertility decisions. Couples marry and divorce partly based on their ability to coordinate these activities, which in turn depends on how well they are matched. This book provides a comprehensive, modern, and self-contained account of the research in the growing area of family economics. The first half of the book develops several alternative models of family decision making. Particular attention is paid to the collective model and its testable implications. The second half discusses household formation and dissolution and who marries whom. Matching models with and without frictions are analyzed and the important role of within-family transfers is explained. The implications for marriage, divorce, and fertility are discussed. The book is intended for graduate students in economics and for researchers in other fields interested in the economic approach to the family\"-- Provided by publisher.
Book
Heat Shock Response in Moss Plants Is Regulated by Specific Calcium-Permeable Channels in the Plasma Membrane
Land plants are prone to strong thermal variations and must therefore sense early moderate temperature increments to induce appropriate cellular defenses, such as molecular chaperones, in anticipation of upcoming noxious temperatures. To investigate how plants perceive mild changes in ambient temperature, we monitored in recombinant lines of the moss Physcomitrella patens the activation of a heat-inducible promoter, the integrity of a thermolabile enzyme, and the fluctuations of cytoplasmic calcium. Mild temperature increments, or isothermal treatments with membrane fluidizers or Hsp90 inhibitors, induced a heat shock response (HSR) that critically depended on a preceding Ca²⁺ transient through the plasma membrane. Electrophysiological experiments revealed the presence of a Ca²⁺-permeable channel in the plasma membrane that is transiently activated by mild temperature increments or chemical perturbations of membrane fluidity. The amplitude of the Ca²⁺ influx during the first minutes of a temperature stress modulated the intensity of the HSR, and Ca²⁺ channel blockers prevented HSR and the onset of thermotolerance. Our data suggest that early sensing of mild temperature increments occurs at the plasma membrane of plant cells independently from cytosolic protein unfolding. The heat signal is translated into an effective HSR by way of a specific membrane-regulated Ca²⁺ influx, leading to thermotolerance.
Journal Article
The Membrane-Associated Transient Receptor Potential Vanilloid Channel Is the Central Heat Shock Receptor Controlling the Cellular Heat Shock Response in Epithelial Cells
The heat shock response (HSR) is a highly conserved molecular response to various types of stresses, including heat shock, during which heat-shock proteins (Hsps) are produced to prevent and repair damages in labile proteins and membranes. In cells, protein unfolding in the cytoplasm is thought to directly enable the activation of the heat shock factor 1 (HSF-1), however, recent work supports the activation of the HSR via an increase in the fluidity of specific membrane domains, leading to activation of heat-shock genes. Our findings support the existence of a plasma membrane-dependent mechanism of HSF-1 activation in animal cells, which is initiated by a membrane-associated transient receptor potential vanilloid receptor (TRPV). We found in various non-cancerous and cancerous mammalian epithelial cells that the TRPV1 agonists, capsaicin and resiniferatoxin (RTX), upregulated the accumulation of Hsp70, Hsp90 and Hsp27 and Hsp70 and Hsp90 respectively, while the TRPV1 antagonists, capsazepine and AMG-9810, attenuated the accumulation of Hsp70, Hsp90 and Hsp27 and Hsp70, Hsp90, respectively. Capsaicin was also shown to activate HSF-1. These findings suggest that heat-sensing and signaling in mammalian cells is dependent on TRPV channels in the plasma membrane. Thus, TRPV channels may be important drug targets to inhibit or restore the cellular stress response in diseases with defective cellular proteins, such as cancer, inflammation and aging.
Journal Article
Enhanced Hsp70 Expression Protects against Acute Lung Injury by Modulating Apoptotic Pathways
The Acute respiratory distress syndrome (ARDS) is a highly lethal inflammatory lung disorder. Apoptosis plays a key role in its pathogenesis. We showed that an adenovirus expressing the 70 kDa heat shock protein Hsp70 (AdHSP) protected against sepsis-induced lung injury. In this study we tested the hypothesis that AdHSP attenuates apoptosis in sepsis-induced lung injury. Sepsis was induced in rats via cecal ligation and double puncture (2CLP). At the time of 2CLP PBS, AdHSP or AdGFP (an adenoviral vector expressing green fluorescent protein) were injected into the tracheas of septic rats. 48 hours later, lungs were isolated. One lung was fixed for TUNEL staining and immunohistochemistry. The other was homogenized to isolate cytosolic and nuclear protein. Immunoblotting, gel filtration and co-immunoprecipitation were performed in these extracts. In separate experiments MLE-12 cells were incubated with medium, AdHSP or AdGFP. Cells were stimulated with TNFα. Cytosolic and nuclear proteins were isolated. These were subjected to immunoblotting, co-immunoprecipitation and a caspase-3 activity assay. TUNEL assay demonstrated that AdHSP reduced alveolar cell apoptosis. This was confirmed by immunohistochemical detection of caspase 3 abundance. In lung isolated from septic animals, immunoblotting, co-immunoprecipitation and gel filtration studies revealed an increase in cytoplasmic complexes containing caspases 3, 8 and 9. AdHSP disrupted these complexes. We propose that Hsp70 impairs apoptotic cellular pathways via interactions with caspases. Disruption of large complexes resulted in stabilization of lower molecular weight complexes, thereby, reducing nuclear caspase-3. Prevention of apoptosis in lung injury may preserve alveolar cells and aid in recovery.
Journal Article
Relocating to a New OR Suite: Practical Observations
Operating room renovation projects usually involve updated technology and processes that can create challenges for administrative leaders (eg, maintaining a surgery schedule during a move) and require staff member adjustments. The perioperative team of a large tertiary care and trauma center relocated from a 35-year-old suite to a new suite, which required years of planning, months of training, and weeks of organizing. This article discusses the processes and observations that helped ensure a smooth transition to the new space. Early planning allowed time for leaders to make equipment decisions, develop and test new processes, and train staff members. The actual move required detailed planning, thorough execution, patience, and flexibility to ensure a safe transition. Perioperative leaders balanced operational needs with relocation plans to maintain patient and staff member safety. Open, multidisciplinary communication combined with staff member participation and buy-in contributed to an efficient, safe move at this facility.
Journal Article
Mechanical ventilation patterns and trends over 20 years in an Israeli hospital system: policy ramifications
Background
Mechanical ventilation is a life supporting modality increasingly utilized when caring for severely ill patients. Its increasing use has extended the survival of the critically ill leading to increasing healthcare expenditures. We examined changes in the hospital-wide use of mechanical ventilation over 20 years (1997–2016) in two Israeli hospitals to determine whether there were specific patterns (e.g. seasonality, weekday vs. weekend) and trends (e.g. increases or decreases) among various hospital departments and units.
Methods
Retrospective analysis of prospectively collected data on all mechanically ventilated patients over 20-years in a two-hospital Israeli medical system was performed. Data were collected for each hospital unit caring for ventilated patients. Time-series analysis examined short and long-term trends, seasonality and intra-week variation.
Results
Over two decades overall ventilator-days increased from 11,164 (31 patients/day) in 1997 to 24,317 (67 patients/day) in 2016 mainly due to more patients ventilated on internal medicine wards (1997: 4 patients/day; 2016: 24 patients/day). The increases in other hospital areas did not approach the magnitude of the internal medicine wards increases. Ventilation on wards reflected the insufficient number of ICU beds in Israel. A detailed snapshot over 4 months of patients ventilated on internal medicine wards (
n
= 745) showed that they tended to be elderly (median age 75 years) and that 24% were ventilated for more than a week. Hospital-wide ventilation patterns were the weighted sum of the various individual patient units with the most noticeable pattern being peak winter prevalence on the internal medical wards and in the emergency department. This seasonality is not surprising, given the greater incidence of respiratory ailments in winter.
Conclusions
Increased mechanical ventilation plus seasonality have budgetary, operational and staffing consequences for individual hospitals and the entire healthcare system. The Israeli healthcare leadership needs to plan and support expanding, equipping and staffing acute and chronic care units that are staffed by providers trained to care for such complex patients.
Journal Article
Moderate Fever Cycles as a Potential Mechanism to Protect the Respiratory System in COVID-19 Patients
Mortality in COVID-19 patients predominantly results from an acute respiratory distress syndrome (ARDS), in which lungs alveolar cells undergo programmed cell death. Mortality in a sepsis-induced ARDS rat model is reduced by adenovirus over-expression of the HSP70 chaperone. A natural rise of body temperature during mild fever can naturally accumulate high cellular levels of HSP70 that can arrest apoptosis and protect alveolar lung cells from inflammatory damages. However, beyond 1-2 h of fever, no HSP70 is being further produced and a decreased in body temperature required to the restore cell's ability to produce more HSP70 in a subsequent fever cycle. We suggest that antipyretics may be beneficial in COVID-19 patients subsequent to several hours of mild (<38.8°C) advantageous fever, allowing lung cells to accumulate protective HSP70 against damages from the inflammatory response to the virus SARS-CoV-2. With age, the ability to develop fever and accumulate HSP70 decreases. This could be ameliorated, when advisable to do so, by thermotherapies and/or physical training.
Journal Article
The effects of etomidate on adrenal responsiveness and mortality in patients with septic shock
Rationale
Use of etomidate in the critically ill is controversial due to its links with an inadequate response to corticotropin and potential for excess mortality. In a septic shock population, we tested the hypotheses that etomidate administration induces more non-responders to corticotropin and increases mortality and that hydrocortisone treatment decreases mortality in patients receiving etomidate.
Methods
An a-priori sub-study of the CORTICUS multi-centre, randomised, double-blind, placebo-controlled trial of hydrocortisone in septic shock. Use and timing of etomidate administration were collected. Endpoints were corticotropin response and all-cause 28-day mortality in patients receiving etomidate.
Measurements and main results
Five hundred patients were recruited, of whom 499 were analysable; 96 (19.2%) were administered etomidate within the 72 h prior to inclusion. The proportion of non-responders to corticotropin was significantly higher in patients who were given etomidate in the 72 h before trial inclusion than in other patients (61.0 vs. 44.6%,
P
= 0.004). Etomidate therapy was associated with a higher 28-day mortality in univariate analysis (
P
= 0.02) and after correction for severity of illness (42.7 vs. 30.5%;
P
= 0.06 and
P
= 0.03) in our two multi-variant models. Hydrocortisone administration did not change the mortality of patients receiving etomidate (45 vs. 40%).
Conclusions
The use of bolus dose etomidate in the 72 h before study inclusion is associated with an increased incidence of inadequate response to corticotropin, but is also likely to be associated with an increase in mortality. We recommend clinicians demonstrate extreme caution in the use of etomidate in critically ill patients with septic shock.
Journal Article
Medical students’ perceptions of a career in family medicine
Background
In Israel, there is a shortage of family medicine (FM) specialists that is occasioned by a shortage of students pursuing a FM career.
Methods
A questionnaire, based on methods adapted from marketing research, was used to provide insight into the medical specialty selection process. It was distributed to 6
th
-year medical students from two Israeli medical schools.
Results
A response rate of 66% resulted in collecting 218 completed questionnaires. Nineteen of the students reported that they were interested in FM, 68% of them were women. When compared to students not interested in FM, the selection criteria of students interested in FM reflected greater interest in a bedside specialty which provides direct long-term patient care. These latter students were also more interested in a controllable lifestyle that allowed time to be with family and children and working outside the hospital especially during the daytime. These selection criteria aligned with their perceptions of FM, which they perceived as providing them with a controllable lifestyle, allowing them to work limited hours with time for family and having a reasonable income to lifestyle ratio. The students not interested in FM, agreed with those interested in FM, that the specialty affords a controllable lifestyle and the ability to work limited hours Yet, students not interested in FM more often perceived FM as being a boring specialty and less often perceived it as providing a reasonable income to lifestyle ratio. Additionally, students not interested in FM rated the selection criteria, academic opportunities and a prestigious specialty, more highly than did students interested in FM. However, they perceived FM as neither being prestigious nor as affording academic opportunities
Conclusion
This study enriches our understanding of the younger generation's attitudes towards FM and thus provides administrators, department chairs and residency program directors with objective information regarding selection criteria and the students’ perceptions of FM. We identified the disconnect between the selection criteria profiles and the perceptions of FM of students not inclined to pursue a residency in FM. This allowed for recommendations on how to possibly make FM more attractive to some of these students.
Journal Article
Utilization of the Public Health Ordinance to prevent nosocomial spread in a case of acute measles-associated psychosis
Measles is a highly contagious disease. A 24 years old patient, recently exposed to measles (unvaccinated), presented in the emergency department with severe agitation, compatible with an acute psychotic episode, during the measles epidemic which spread in Israel in 2018–2019. Upon hospital admission, strict isolation was instructed, yet, without compliance, probably due to the patient’s status. Measles diagnosis was promptly confirmed. As measles transmission was eminent, public health measures were employed through immediate implementation of the section 15 of the Public Health Ordinance, allowing for compulsory short-term isolation. The patient’s condition improved within a few days and the measures were no longer necessary. This measles case occurred in the pre-Coronavirus disease 2019 (COVID-19) epidemic when use of a Public Health Ordinance was considered an extreme measure. This is in contrast to the current global use of Public Health laws to enforce strict quarantine and isolation on persons infected or potentially exposed to COVID-19. Nevertheless, minimizing infectious diseases transmission is a core function of public health law. Utilizing legal enforcement in circumstances of immediate public health hazard, such as nosocomial measles transmission, necessitates careful consideration. The integrative clinical and public health approach and prompt measures employed in this exceptional case, led to prevention of further infection spread.
Journal Article