Integrated behavioral health model for COVID-19 patients

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An integrated behavioral health to non-communicable disease in Cambodia

Noncommunicable diseases (NCD’s) such as type 2 diabetes and hypertension are increasing in Cambodia. Clinicians in Cambodia do not routinely offer behavioral interventions to address the lifestyle behaviors such as poor nutrition, lack of physical activity and tobacco smoking that contribute to poor outcomes for NCD’s. Behavioral conditions such as depression and substance use disorder that are frequently comorbid with NCD’s also contribute to poor clinical outcomes are also not routinely addressed in medical settings in Cambodia. Integrated healthcare is the systematic, team-based approach to delivering behavioral interventions to address lifestyle and behavioral conditions that underlie poor outcomes for NCD’s delivered by a Behavioral Health Consultant (BHC). Research on type 2 diabetes and hypertension risk factors such as nutrition, physical activity, tobacco smoking and alcohol misuse demonstrates the need for a new workforce of BHC’s to improve quality and outcomes. A model of integrated behavioral health designed by this research team uses a Health Risk Assessment, a social worker or community health worker in the BHC role, and smartphone app platform for patient health self-management is recommended

Interleukin-1β Maturation Triggers Its Relocation to the Plasma Membrane for Gasdermin-D-Dependent and -Independent Secretion

IL-1β requires processing by caspase-1 to generate the active, pro-inflammatory cytokine. Acute IL-1β secretion from inflammasome-activated macrophages requires caspase-1-dependent GSDMD cleavage, which also induces pyroptosis. Mechanisms of IL-1β secretion by pyroptotic and non-pyroptotic cells, and the precise functions of caspase-1 and GSDMD therein, are unresolved. Here, we show that, while efficient early secretion of endogenous IL-1β from primary non-pyroptotic myeloid cells in vitro requires GSDMD, later IL-1β release in vitro and in vivo proceeds independently of GSDMD. IL-1β maturation is sufficient for slow, caspase-1/GSDMD-independent secretion of ectopic IL-1β from resting, non-pyroptotic macrophages, but the speed of IL-1β release is boosted by inflammasome activation, via caspase-1 and GSDMD. IL-1β cleavage induces IL-1β enrichment at PIP2-enriched plasma membrane ruffles, and this is a prerequisite for IL-1β secretion and is mediated by a polybasic motif within the cytokine. We thus reveal a mechanism in which maturation-induced IL-1β trafficking facilitates its unconventional secretion

AIDS-related mycoses: the way forward.

The contribution of fungal infections to the morbidity and mortality of HIV-infected individuals is largely unrecognized. A recent meeting highlighted several priorities that need to be urgently addressed, including improved epidemiological surveillance, increased availability of existing diagnostics and drugs, more training in the field of medical mycology, and better funding for research and provision of treatment, particularly in developing countries

ECMO for COVID-19 patients in Europe and Israel

Since March 15th, 2020, 177 centres from Europe and Israel have joined the study, routinely reporting on the ECMO support they provide to COVID-19 patients. The mean annual number of cases treated with ECMO in the participating centres before the pandemic (2019) was 55. The number of COVID-19 patients has increased rapidly each week reaching 1531 treated patients as of September 14th. The greatest number of cases has been reported from France (n = 385), UK (n = 193), Germany (n = 176), Spain (n = 166), and Italy (n = 136) .The mean age of treated patients was 52.6 years (range 16–80), 79% were male. The ECMO configuration used was VV in 91% of cases, VA in 5% and other in 4%. The mean PaO2 before ECMO implantation was 65 mmHg. The mean duration of ECMO support thus far has been 18 days and the mean ICU length of stay of these patients was 33 days. As of the 14th September, overall 841 patients have been weaned from ECMO support, 601 died during ECMO support, 71 died after withdrawal of ECMO, 79 are still receiving ECMO support and for 10 patients status n.a. . Our preliminary data suggest that patients placed on ECMO with severe refractory respiratory or cardiac failure secondary to COVID-19 have a reasonable (55%) chance of survival. Further extensive data analysis is expected to provide invaluable information on the demographics, severity of illness, indications and different ECMO management strategies in these patients

Estimation of mean health care costs and incremental cost-effectiveness ratios with possibly censored data

In this article, we describe the hcost program for estimating mean health care costs and incremental cost-effectiveness ratios with possibly censored data. hcost estimates the mean survival time and the mean costs, as well as their variances and covariance, for a given time horizon. If the group variable is specified, hcost will report the differences between two groups, as well as the incremental cost-effectiveness ratio and its confidence interval (optional). hcost can estimate the mean costs using two methods corresponding to different types of data: the Bang and Tsiatis (2000, Biometrika 87: 329–343) estimator using only the total costs or the Zhao and Tian (2001, Biometrics 57: 1002–1008) estimator when cost-history data are available. The hcost program can also be used to specify the annual discounting rates for survival time and costs

DNA-Bound Bas1 Recruits Pho2 To Activate ADE Genes in Saccharomyces cerevisiae

Expression of the genes in the ADE regulon of Saccharomyces cerevisiae is repressed by the presence of purine bases in the extracellular medium and derepressed when cells are grown in the absence of purines. Derepression requires the transcriptional activators Bas1 and Pho2, as well as the biosynthetic intermediates 5′-phosphoribosyl-4-succinocarboxamide-5-aminoimidazole (SAICAR) and 5′-phosphoribosyl-4-carboxamide- 5-aminoimidazole (AICAR). In this study, we investigated if nuclear localization and binding to promoter DNA by the activators are regulated by purines. Using indirect immunofluorescence, we found that Bas1 is localized to the nucleus under both repressing and derepressing conditions. Importantly, we detected Bas1 bound to promoter DNA under both conditions using chromatin immunoprecipitation assays at several ADE promoters (ADE1, ADE2, ADE4, and ADE5,7) and HIS4. We analyzed the binding of Bas1 to wild-type and mutant sequences of the ADE5,7 promoters in vivo, and found that Bas1 binds independently to each of its two binding sites. Pho2 was not required for the association of Bas1 with chromosomal DNA, but it was required for an increase in Bas1-immunoprecipitated DNA. The presence of Pho2 at promoters was dependent on Bas1 and occurred only under derepressing conditions when the ADE genes are transcribed at elevated levels. We propose a model for regulation of the ADE genes in which DNA-bound Bas1 is inactive due to masking of its activation domain and Pho2 binds poorly to promoters when cells have sufficient purine nucleotides. Upon limitation for purines, the SAICAR/AICAR regulatory signal is transmitted to the nucleus to increase Bas1 and Pho2 interaction, recruiting Pho2 to promoters and freeing the activation domains for transactivation

Dynamics of Geometrically-Nonlinear Beam Structures, Part 1: Numerical Modeling

editorial reviewedThe need of lightweight design in structural engineering is steadily growing due to economic and ecological reasons. This usually causes the structure to exhibit moderate to large displacements and rotations, resulting in a distributed nonlinear behavior. However, the characterization of geometrical nonlinearities is challenging and sensitive to structural boundaries and loading. It is commonly performed with numerical simulations, utilizing particularly finite element formulations. This study comprises simulations of a clamped-clamped beam with moderate to large amplitude oscillations. Four different (commercial and noncommercial) numerical approaches are considered: three finite element representations and one assumed-modes approach. A first comparison is conducted when the system is under a sine sweep excitation over one single mode. Subsequently, a modified model featuring nonlinear internal resonance is considered, to disclose differences in the modeling of the nonlinearity when coupling between modes occurs. The results show some expected features for geometrical nonlinearities in all methods, but also some important differences, especially when the modal interaction is activated

Fracture incidence in Ehlers-Danlos syndrome – A population-based case-control study

BackgroundThe differential diagnosis of non-accidental injury during childhood includes medical conditions that predispose to skeletal fragility. Ehlers-Danlos syndrome (EDS) has been proposed as one such condition despite little objective evidence in the medical literature.ObjectiveTo investigate if EDS causes increased bone fragility during infancy and childhood.Participants and settingResidents of an 8-county region in southern Minnesota using the Rochester Epidemiology Project (REP) medical records-linkage system.MethodsThis retrospective, population-based, case-control study identified subjects with EDS from 1976 to 2015 who had complete records for at least their first year of life. Validity of diagnosis was ascertained using the 2017 International Classification of the Ehlers-Danlos Syndromes. Records were reviewed for fracture diagnoses that were characterized by age, location, type and mechanism.ResultsOf 219 potential cases, 21 had complete records for the first year of life and sufficient evidence in the medical record to support an EDS diagnosis. Of these 21, there were 14 hypermobile, 2 classical, 4 vascular, and 1 arthrochalasia EDS subtypes. 11 of 21 EDS cases (52.4%) and 15 of 63 controls (23.8%) had one or more fractures during childhood. No fractures were identified in the first year of life. Comparing cases to controls, EDS was associated with having any fractures during childhood with an odds ratio of 3.4 (95% CI: 1.20-9.66).ConclusionsWe found no evidence that infants with common forms of EDS are predisposed to more frequent fractures. Ambulatory subjects with these EDS subtypes may have a higher incidence of fractures during childhood