Inundation Impact Index for Disaster Risk Assessment

Source: ICHE Conference Archive - https://mdi-de.baw.de/icheArchiv

THE IMPACT OF COVID-19 ON INFORMAL CAREGIVERS IN THE US

Background: Caregiver burden has negative effects on mental and physical health along with quality of life. Meanwhile, social and physical distancing protocols during the COVID-19 pandemic have created additional impacts on informal caregiving in a rapidly changing environment. Early research over the past year suggests that the pandemic has caused increased caregiver burden as well as caregiving intensity among these individuals. Purpose: Our primary purpose in this informational literature review is to describe the impacts of the pandemic on informal caregiver burden and the sudden shift in roles and responsibilities as a result of pandemic-related changes in caregiving. This review will describe emerging effects on various aspects of health among informal caregivers and explore the growing need to support unpaid caregiving during this time. Methods: A streamlined search was conducted to fit the scope of this review, with key terms determined to identify relevant publications. Common research databases and up-to-date mainstream resources were utilized. Notably, we focused on research published or released since March 2020, primarily rapidly reviewed studies, to align with the timing of the COVID-19 pandemic in the US. Results: Early research suggests that the pandemic has worsened caregiver burden and increased caregiving intensity and hours of care among unpaid, informal family caregivers. Reported health impacts include higher stress, pain, and depression, along with decreased social connectedness and quality of life. Notably, however, COVID-related research generally does not focus on the positive aspects of caregiving, such as its role as a source of purpose in life, creating an opportunity to explore ways to boost certain valuable personal resources among caregivers. Conclusions: Informal family caregivers face their own negative health outcomes and distress as a result of greater caregiver burden, intensity, and the changing landscape of caregiving during the ongoing COVID-19 pandemic. Immediate policy and support recommendations should be considered to alleviate informal caregiver burden and provide ongoing resources over the longer term. In addition, future work should explore the potential of boosting positive resources such as resilience and purpose to ease caregiver burden

Association of Medical Students' Reports of Interactions with the Pharmaceutical and Medical Device Industries and Medical School Policies and Characteristics: A Cross-Sectional Study

Background: Professional societies use metrics to evaluate medical schools' policies regarding interactions of students and faculty with the pharmaceutical and medical device industries. We compared these metrics and determined which US medical schools' industry interaction policies were associated with student behaviors. Methods and Findings: Using survey responses from a national sample of 1,610 US medical students, we compared their reported industry interactions with their schools' American Medical Student Association (AMSA) PharmFree Scorecard and average Institute on Medicine as a Profession (IMAP) Conflicts of Interest Policy Database score. We used hierarchical logistic regression models to determine the association between policies and students' gift acceptance, interactions with marketing representatives, and perceived adequacy of faculty–industry separation. We adjusted for year in training, medical school size, and level of US National Institutes of Health (NIH) funding. We used LASSO regression models to identify specific policies associated with the outcomes. We found that IMAP and AMSA scores had similar median values (1.75 [interquartile range 1.50–2.00] versus 1.77 [1.50–2.18], adjusted to compare scores on the same scale). Scores on AMSA and IMAP shared policy dimensions were not closely correlated (gift policies, r = 0.28, 95% CI 0.11–0.44; marketing representative access policies, r = 0.51, 95% CI 0.36–0.63). Students from schools with the most stringent industry interaction policies were less likely to report receiving gifts (AMSA score, odds ratio [OR]: 0.37, 95% CI 0.19–0.72; IMAP score, OR 0.45, 95% CI 0.19–1.04) and less likely to interact with marketing representatives (AMSA score, OR 0.33, 95% CI 0.15–0.69; IMAP score, OR 0.37, 95% CI 0.14–0.95) than students from schools with the lowest ranked policy scores. The association became nonsignificant when fully adjusted for NIH funding level, whereas adjusting for year of education, size of school, and publicly versus privately funded school did not alter the association. Policies limiting gifts, meals, and speaking bureaus were associated with students reporting having not received gifts and having not interacted with marketing representatives. Policy dimensions reflecting the regulation of industry involvement in educational activities (e.g., continuing medical education, travel compensation, and scholarships) were associated with perceived separation between faculty and industry. The study is limited by potential for recall bias and the cross-sectional nature of the survey, as school curricula and industry interaction policies may have changed since the time of the survey administration and study analysis. Conclusions: As medical schools review policies regulating medical students' industry interactions, limitations on receipt of gifts and meals and participation of faculty in speaking bureaus should be emphasized, and policy makers should pay greater attention to less research-intensive institutions. Please see later in the article for the Editors' Summar

tGBS® genotyping-by-sequencing enables reliable genotyping of heterozygous loci

Conventional genotyping-by-sequencing (cGBS) strategies suffer from high rates of missing data and genotyping errors, particularly at heterozygous sites. tGBS® genotyping-by-sequencing is a novel method of genome reduction that employs two restriction enzymes to generate overhangs in opposite orientations to which (single-strand) oligos rather than (double-stranded) adaptors are ligated. This strategy ensures that only doubledigested fragments are amplified and sequenced. The use of oligos avoids the necessity of preparing adaptors and the problems associated with inter-adaptor annealing/ligation. Hence, the tGBS protocol simplifies the preparation of high-quality GBS sequencing libraries. During polymerase chain reaction (PCR) amplification, selective nucleotides included at the 3\u27-end of the PCR primers result in additional genome reduction as compared to cGBS. By adjusting the number of selective bases, different numbers of genomic sites are targeted for sequencing. Therefore, for equivalent amounts of sequencing, more reads per site are available for SNP calling. Hence, as compared to cGBS, tGBS delivers higher SNP calling accuracy (\u3e97–99%), even at heterozygous sites, less missing data per marker across a population of samples, and an enhanced ability to genotype rare alleles. tGBS is particularly well suited for genomic selection, which often requires the ability to genotype populations of individuals that are heterozygous at many loci

Protein Kinase B Regulates T Lymphocyte Survival, Nuclear Factor κb Activation, and Bcl-XL Levels in Vivo

The serine/threonine kinase protein kinase B (PKB)/Akt mediates cell survival in a variety of systems. We have generated transgenic mice expressing a constitutively active form of PKB (gag-PKB) to examine the effects of PKB activity on T lymphocyte survival. Thymocytes and mature T cells overexpressing gag-PKB displayed increased active PKB, enhanced viability in culture, and resistance to a variety of apoptotic stimuli. PKB activity prolonged the survival of CD4+CD8+ double positive (DP) thymocytes in fetal thymic organ culture, but was unable to prevent antigen-induced clonal deletion of thymocytes expressing the major histocompatibility complex class I–restricted P14 T cell receptor (TCR). In mature T lymphocytes, PKB can be activated in response to TCR stimulation, and peptide-antigen–specific proliferation is enhanced in T cells expressing the gag-PKB transgene. Both thymocytes and T cells overexpressing gag-PKB displayed elevated levels of the antiapoptotic molecule Bcl-XL. In addition, the activation of peripheral T cells led to enhanced nuclear factor (NF)-κB activation via accelerated degradation of the NF-κB inhibitory protein IκBα. Our data highlight a physiological role for PKB in promoting survival of DP thymocytes and mature T cells, and provide evidence for the direct association of three major survival molecules (PKB, Bcl-XL, and NF-κB) in vivo in T lymphocytes

Intragenic Meiotic Crossovers Generate Novel Alleles with Transgressive Expression Levels

Meiotic recombination is an evolutionary force that generates new genetic diversity upon which selection can act. Whereas multiple studies have assessed genome-wide patterns of recombination and specific cases of intragenic recombination, few studies have assessed intragenic recombination genome-wide in higher eukaryotes. We identified recombination events within or near genes in a population of maize recombinant inbred lines (RILs) using RNA-sequencing data. Our results are consistent with case studies that have shown that intragenic crossovers cluster at the 5\u27 ends of some genes. Further, we identified cases of intragenic crossovers that generate transgressive transcript accumulation patterns, that is, recombinant alleles displayed higher or lower levels of expression than did nonrecombinant alleles in any of ~100 RILs, implicating intragenic recombination in the generation of new variants upon which selection can act. Thousands of apparent gene conversion events were identified, allowing us to estimate the genome-wide rate of gene conversion at SNP sites (4.9 X 10-5). The density of syntenic genes (i.e., those conserved at the same genomic locations since the divergence of maize and sorghum) exhibits a substantial correlation with crossover frequency, whereas the density of nonsyntenic genes (i.e., those which have transposed or been lost subsequent to the divergence of maize and sorghum) shows little correlation, suggesting that crossovers occur at higher rates in syntenic genes than in nonsyntenic genes. Increased rates of crossovers in syntenic genes could be either a consequence of the evolutionary conservation of synteny or a biological process that helps to maintain synteny

Nematic liquid crystal alignment on chemical patterns

Patterned Self-Assembled Monolayers (SAMs) promoting both homeotropic and planar degenerate alignment of 6CB and 9CB in their nematic phase, were created using microcontact printing of functionalised organothiols on gold films. The effects of a range of different pattern geometries and sizes were investigated, including stripes, circles and checkerboards. EvanescentWave Ellipsometry was used to study the orientation of the liquid crystal (LC) on these patterned surfaces during the isotropic-nematic phase transition. Pretransitional growth of a homeotropic layer was observed on 1 ¹m homeotropic aligning stripes, followed by a homeotropic mono-domain state prior to the bulk phase transition. Accompanying Monte-Carlo simulations of LCs aligned on nano-patterned surfaces were also performed. These simulations also showed the presence of the homeotropic mono-domain state prior to the transition.</p

Fas signaling induces raft coalescence that is blocked by cholesterol depletion in human RPE cells undergoing apoptosis

PURPOSE. To investigate whether the signaling events occurring in Fas-mediated apoptosis alter raft membrane formation in human RPE cells. METHODS. Formation of lipid rafts in cultured human retinal pigment epithelial cells (ARPE-19) was studied by confocal microscopy, with fluorescein-labeled cholera toxin subunit B binding protein (BODIPY)-labeled ganglioside GM1 lipid after Fas-L induction of apoptosis. Apoptosis was assessed by fluorescein-labeled annexin V detection of phosphatidylserine externalization and quadrant analysis with flow cytometry. Membrane rafts were localized into membrane vesicles by passing BODIPY-labeled GM1 RPE cells through a 2-m-pore polycarbonate membrane using an extruder device. The labeled fractions, containing vesicles enriched in GM1, were detected by flow cytometry and then analyzed for the presence of Fas protein. RESULTS. Differential punctate staining of membrane rafts was demonstrated in normal and FasL-induced apoptotic human ARPE-19 cells in culture by confocal microscopy, using cholera toxin B and GM1 labeling of extruded vesicles. The lipid raftassociated vesicles were derived by plasma membrane dissociation, via a newly developed whole-cell extrusion technique that produced 2-m vesicles with both GM1 lipid and Fas protein abundance enriched in a subpopulation of the membrane-derived vesicles. The amount of Fas protein in the vesicles containing raft domains markedly increased in FasL-treated cells. Treatment of human ARPE 19 cells with methyl ␤-cyclodextrin after FasL induction of apoptosis resulted in cellular cholesterol depletion and markedly reduced the incidence of Fas-receptor localization in GM1 rafts. CONCLUSIONS. Human ARPE-19 cells in culture contain membrane rafts with apoptotic signaling effectors uniformly distributed in the native state. The cells stimulated to undergo apoptosis appear to use membrane rafts in the death-signaling process by mobilization of rafts to localized regions of the membrane that are now enriched with apoptotic signaling effectors. Fas signaling induces apoptotic raft formation that results in polar condensation, or capping, of the rafts in the late stages of apoptosis. A novel extrusion technique is described that allows localization and enrichment of rafts into membrane vesicles, which can be assayed by flow cytometry. Cholesterol depletion, after Fas ligand activation of apoptosis, reduced raft formation in cells induced to undergo apoptosis. Therapeutic implications for the treatment of retinal disorders are discussed. (Invest Ophthalmol Vis Sci

CD28-dependent Activation of Protein Kinase B/Akt Blocks Fas-mediated Apoptosis by Preventing Death-inducing Signaling Complex Assembly

The T cell costimulatory molecule CD28 is important for T cell survival, yet both the signaling pathways downstream of CD28 and the apoptotic pathways they antagonize remain poorly understood. Here we demonstrate that CD4+ T cells from CD28-deficient mice show increased susceptibility to Fas-mediated apoptosis via a phosphatidylinositol 3-kinase (PI3K)-dependent pathway. Protein kinase B (PKBα/Akt1) is an important serine/threonine kinase that promotes survival downstream of PI3K signals. To understand how PI3K-mediated signals downstream of CD28 contribute to T cell survival, we examined Fas-mediated apoptosis in T cells expressing an active form of PKBα. Our data demonstrate that T cells expressing active PKB are resistant to Fas-mediated apoptosis in vivo and in vitro. PKB transgenic T cells show reduced activation of caspase-8, BID, and caspase-3 due to impaired recruitment of procaspase-8 to the death-inducing signaling complex (DISC). Similar alterations are seen in T cells from mice which are haploinsufficient for PTEN, a lipid phosphatase that regulates phosphatidylinositol-3,4,5-trisphosphate (PIP3) and influences PKBα activity. These findings provide a novel link between CD28 and an important apoptosis pathway in vivo, and demonstrate that PI3K/PKB signaling prevents apoptosis by inhibiting DISC assembly