Cost-Effective Control of Infectious Disease Outbreaks Accounting for Societal Reaction

Background Studies of cost-effective disease prevention have typically focused on the tradeoff between the cost of disease transmission and the cost of applying control measures. We present a novel approach that also accounts for the cost of social disruptions resulting from the spread of disease. These disruptions, which we call social response, can include heightened anxiety, strain on healthcare infrastructure, economic losses, or violence. Methodology The spread of disease and social response are simulated under several different intervention strategies. The modeled social response depends upon the perceived risk of the disease, the extent of disease spread, and the media involvement. Using Monte Carlo simulation, we estimate the total number of infections and total social response for each strategy. We then identify the strategy that minimizes the expected total cost of the disease, which includes the cost of the disease itself, the cost of control measures, and the cost of social response. Conclusions The model-based simulations suggest that the least-cost disease control strategy depends upon the perceived risk of the disease, as well as media intervention. The most cost-effective solution for diseases with low perceived risk was to implement moderate control measures. For diseases with higher perceived severity, such as SARS or Ebola, the most cost-effective strategy shifted toward intervening earlier in the outbreak, with greater resources. When intervention elicited increased media involvement, it remained important to control high severity diseases quickly. For moderate severity diseases, however, it became most cost-effective to implement no intervention and allow the disease to run its course. Our simulation results imply that, when diseases are perceived as severe, the costs of social response have a significant influence on selecting the most cost-effective strategy.United States. Defense Threat Reduction Agency (Contract HDTRA1-12-C-0061

Repositioning of Verrucosidin, a purported inhibitor of chaperone protein GRP78, as an inhibitor of mitochondrial electron transport chain complex I.

Verrucosidin (VCD) belongs to a group of fungal metabolites that were identified in screening programs to detect molecules that preferentially kill cancer cells under glucose-deprived conditions. Its mode of action was proposed to involve inhibition of increased GRP78 (glucose regulated protein 78) expression during hypoglycemia. Because GRP78 plays an important role in tumorigenesis, inhibitors such as VCD might harbor cancer therapeutic potential. We therefore sought to characterize VCD's anticancer activity in vitro. Triple-negative breast cancer cell lines MDA-MB-231 and MDA-MB-468 were treated with VCD under different conditions known to trigger increased expression of GRP78, and a variety of cellular processes were analyzed. We show that VCD was highly cytotoxic only under hypoglycemic conditions, but not in the presence of normal glucose levels, and VCD blocked GRP78 expression only when glycolysis was impaired (due to hypoglycemia or the presence of the glycolysis inhibitor 2-deoxyglucose), but not when GRP78 was induced by other means (hypoxia, thapsigargin, tunicamycin). However, VCD's strictly hypoglycemia-specific toxicity was not due to the inhibition of GRP78. Rather, VCD blocked mitochondrial energy production via inhibition of complex I of the electron transport chain. As a result, cellular ATP levels were quickly depleted under hypoglycemic conditions, and common cellular functions, including general protein synthesis, deteriorated and resulted in cell death. Altogether, our study identifies mitochondria as the primary target of VCD. The possibility that other purported GRP78 inhibitors (arctigenin, biguanides, deoxyverrucosidin, efrapeptin, JBIR, piericidin, prunustatin, pyrvinium, rottlerin, valinomycin, versipelostatin) might act in a similar GRP78-independent fashion will be discussed

SBG Applications: Public Health and Urban Environments

No abstract availabl

Walker use, but not falls, is associated with lower physical functioning and health of residents in an assisted-living environment

The relationship between perceived health and walker use has seldom been addressed. Concerns over falls and falls risk are precursors to walker use. We compared the SF-36 scores of 26 women and 14 men, mean age 86.8 ± 6.0 years based on walker use and faller status. An analysis of covariance (ANCOVA) with age as the covariate, compared groups for the SF-36 constructs and totals score. Significant differences were noted between walker users and nonusers in physical functioning, role limitations due to physical problems, general health, and the total SF-36 score. Pairwise comparisons favored nonusers, while no differences were seen due to faller status. Walker use is associated with lower self-perceptions of physical functioning, role limitations due to physical problems, and general health in assisted-living residents. Faller status is not associated with self-perceived health status. Although walker use aids mobility and lowers the probability of falls, further research is needed to determine if the prescription of assistive devices has a more negative impact on self-perceived health than does falling. This possibility could be explained, in part, by the greater activity levels of those individuals who do not depend on walkers

Associations of online religious participation during COVID-19 lockdown with subsequent health and well-being among UK adults.

Background In-person religious service attendance has been linked to favorable health and well-being outcomes. However, little research has examined whether online religious participation improves these outcomes, especially when in-person attendance is suspended. Methods Using longitudinal data of 8951 UK adults, this study prospectively examined the association between frequency of online religious participation during the stringent lockdown in the UK (23 March –13 May 2020) and 21 indicators of psychological well-being, social well-being, pro-social/altruistic behaviors, psychological distress, and health behaviors. All analyses adjusted for baseline socio-demographic characteristics, pre-pandemic in-person religious service attendance, and prior values of the outcome variables whenever data were available. Bonferroni correction was used to correct for multiple testing. Results Individuals with online religious participation of ≥1/week (v. those with no participation at all) during the lockdown had a lower prevalence of thoughts of self-harm in week 20 (odds ratio 0.24; 95% CI 0.09–0.62). Online religious participation of <1/week (v. no participation) was associated with higher life satisfaction (standardized β = 0.25; 0.11–0.39) and happiness (standardized β = 0.25; 0.08–0.42). However, there was little evidence for the associations between online religious participation and all other outcomes (e.g. depressive symptoms and anxiety). Conclusions There was evidence that online religious participation during the lockdown was associated with some subsequent health and well-being outcomes. Future studies should examine mechanisms underlying the inconsistent results for online v. in-person religious service attendance and also use data from non-pandemic situations

Addressing Occupational Deprivation in Refugees: A Scoping Review

In 2015, over 21 million refugees were displaced worldwide. A significant issue faced by this population is occupational deprivation – being deprived of engagement in meaningful activities. Despite this being a global problem, information on interventions that address occupational deprivation has not been synthesized. To bridge this gap, we conducted a scoping review to examine interventions that can be used when working with refugees who face this issue. For our methods, we used a five-step framework and reviewed interventions using the following databases: PubMed, CINAHL, PsycINFO, and Google Scholar. Initial searches yielded 191 studies, 7 of which were retained. Community-based rehabilitation, familiar activities from native countries, projective techniques allowing for emotional expression, mastery of practical skills allowing for navigation in new environments, and activities that promote social participation can be used with refugees who face occupational deprivation. These interventions may help promote refugees’ engagement in activities that hold personal, social, and cultural meaning

Excess ribosomal protein production unbalances translation in a model of Fragile X Syndrome

Dysregulated protein synthesis is a core pathogenic mechanism in Fragile X Syndrome (FX). The mGluR Theory of FX predicts that pathological synaptic changes arise from the excessive translation of mRNAs downstream of mGlu1/5 activation. Here, we use a combination of CA1 pyramidal neuron-specific TRAP-seq and proteomics to identify the overtranslating mRNAs supporting exaggerated mGlu1/5 -induced long-term synaptic depression (mGluR-LTD) in the FX mouse model (Fmr1−/y). Our results identify a significant increase in the translation of ribosomal proteins (RPs) upon mGlu1/5 stimulation that coincides with a reduced translation of long mRNAs encoding synaptic proteins. These changes are mimicked and occluded in Fmr1−/y neurons. Inhibiting RP translation significantly impairs mGluR-LTD and prevents the length-dependent shift in the translating population. Together, these results suggest that pathological changes in FX result from a length-dependent alteration in the translating population that is supported by excessive RP translation

Oral rehydration versus intravenous therapy for treating dehydration due to gastroenteritis in children: a meta-analysis of randomised controlled trials

BACKGROUND: Despite treatment recommendations from various organizations, oral rehydration therapy (ORT) continues to be underused, particularly by physicians in high-income countries. We conducted a systematic review of randomised controlled trials (RCTs) to compare ORT and intravenous therapy (IVT) for the treatment of dehydration secondary to acute gastroenteritis in children. METHODS: RCTs were identified through MEDLINE, EMBASE, CENTRAL, authors and references of included trials, pharmaceutical companies, and relevant organizations. Screening and inclusion were performed independently by two reviewers in order to identify randomised or quasi-randomised controlled trials comparing ORT and IVT in children with acute diarrhea and dehydration. Two reviewers independently assessed study quality using the Jadad scale and allocation concealment. Data were extracted by one reviewer and checked by a second. The primary outcome measure was failure of rehydration. We analyzed data using standard meta-analytic techniques. RESULTS: The quality of the 14 included trials ranged from 0 to 3 (Jadad score); allocation concealment was unclear in all but one study. Using a random effects model, there was no significant difference in treatment failures (risk difference [RD] 3%; 95% confidence intervals [CI]: 0, 6). The Mantel-Haenzsel fixed effects model gave a significant difference between treatment groups (RD 4%; 95% CI: 2, 5) favoring IVT. Based on the four studies that reported deaths, there were six in the IVT groups and two in ORT. There were no significant differences in total fluid intake at six and 24 hours, weight gain, duration of diarrhea, or hypo/hypernatremia. Length of stay was significantly shorter for the ORT group (weighted mean difference [WMD] -1.2 days; 95% CI: -2.4,-0.02). Phlebitis occurred significantly more often with IVT (number needed to treat [NNT] 33; 95% CI: 25,100); paralytic ileus occurred more often with ORT (NNT 33; 95% CI: 20,100). These results may not be generalizable to children with persistent vomiting. CONCLUSION: There were no clinically important differences between ORT and IVT in terms of efficacy and safety. For every 25 children (95% CI: 20, 50) treated with ORT, one would fail and require IVT. The results support existing practice guidelines recommending ORT as the first course of treatment in appropriate children with dehydration secondary to gastroenteritis

Classecol: classifiers to understand public opinions of nature

1) Human perceptions of nature, once the domain of the social sciences, are now an important part of environmental research. However, the data and tools to tackle this research are lacking or are difficult to apply. 2) Here, we present a collection of text classifier models to identify text relevant to the broad topics of hunting and nature, describing whether opinions are pro- or against-hunting, or show interest, concern, or dislike of nature. The methods also include a biographical classification – describing whether the author of the text is a person, nature expert, nature organisation, or ‘Other’. The classifiers were developed using an extensive social media dataset, and are designed to support qualitative analysis of big data (especially from Twitter). 3) The classifiers accurately identified biographies, text related to hunting and nature, and the stance towards hunting and nature (weighted F-scores: 0.79 - 0.99; 1 indicates perfect accuracy). 4) These classifiers, alongside an array of other text processing and analysis functions, are presented in the form of an R package classecol. classecol also acts as a proof of concept that nature related text classifiers can be developed with high accuracy

Limbal BCAM expression identifies a proliferative progenitor population capable of holoclone formation and corneal differentiation

The corneal epithelium is renowned for high regenerative potential, which is dependent on the coordinated function of its diverse progenitor subpopulations. However, the molecular pathways governing corneal epithelial progenitor differentiation are incompletely understood. Here, we identify a highly proliferative limbal epithelial progenitor subpopulation characterized by expression of basal cell adhesion molecule (BCAM) that is capable of holocone formation and corneal epithelial sheet generation. BCAM-positive cells can be found among ABCB5-positive limbal stem cells (LSCs) as well as among ABCB5-negative limbal epithelial cell populations. Mechanistically, we show that BCAM is functionally required for cellular migration and differentiation and that its expression is regulated by the transcription factor p63. In aggregate, our study identifies limbal BCAM expression as a marker of highly proliferative corneal epithelial progenitor cells and defines the role of BCAM as a critical molecular mediator of corneal epithelial differentiation