1,139 research outputs found
Women’s Behavioral Responses to the Threat of a Hypothetical Date Rape Stimulus: A Qualitative Analysis
One in four college women experience sexual assault on campus; yet, campuses rarely provide the in-depth self-defense programs needed to reduce sexual assault risk. Further, little is known about the range of possible behaviors elicited by sexual assault threat stimuli besides assertion. To fill this gap, the aim of the current study was to explore qualitative themes in women’s intended behavioral responses to a hypothetical sexual assault threat, date rape, by using a laboratory-controlled threat. College women (N = 139) were randomly assigned to one of four different levels of sexual assault threat presented via an audio-recorded vignette. Participants articulated how they would hypothetically respond to the experimentally assigned threat. Responses were blinded and analyzed using Consensual Qualitative Research methodology. Six major themes emerged: assertion, compliance/acceptance, conditional decision making, avoidance, expressions of discomfort, and allusion to future contact. Although almost all participants described assertion, a number of non-assertive responses were described that are not currently recognized in the literature. These non-assertive responses, including compliance/acceptance, conditional decision making, and avoidance, may represent unique behavioral response styles and likely reflect the complex psychological process of behavioral response to threat. The variety of themes found illustrates the great range of behavioral responses to threat. This broad range is not currently well represented or measured in the literature and better understanding of these responses can inform future interventions, advocacy efforts, and policies focused on sexual assault
Phosphonopeptides Revisited, in an Era of Increasing Antimicrobial Resistance
Given the increase in resistance to antibacterial agents, there is an urgent need for the development of new agents with novel modes of action. As an interim solution, it is also prudent to reinvestigate old or abandoned antibacterial compounds to assess their efficacy in the context of widespread resistance to conventional agents. In the 1970s, much work was performed on the development of peptide mimetics, exemplified by the phosphonopeptide, alafosfalin. We investigated the activity of alafosfalin, di-alanyl fosfalin and β-chloro-L-alanyl-β-chloro-L-alanine against 297 bacterial isolates, including carbapenemase-producing Enterobacterales (CPE) (n = 128), methicillin-resistant Staphylococcus aureus (MRSA) (n = 37) and glycopeptide-resistant enterococci (GRE) (n = 43). The interaction of alafosfalin with meropenem was also examined against 20 isolates of CPE. The MIC50 and MIC90 of alafosfalin for CPE were 1 mg/L and 4 mg/L, respectively and alafosfalin acted synergistically when combined with meropenem against 16 of 20 isolates of CPE. Di-alanyl fosfalin showed potent activity against glycopeptide-resistant isolates of Enterococcus faecalis (MIC90; 0.5 mg/L) and Enterococcus faecium (MIC90; 2 mg/L). Alafosfalin was only moderately active against MRSA (MIC90; 8 mg/L), whereas β-chloro-L-alanyl-β-chloro-L-alanine was slightly more active (MIC90; 4 mg/L). This study shows that phosphonopeptides, including alafosfalin, may have a therapeutic role to play in an era of increasing antibacterial resistance
Social facilitation in virtual reality-enhanced exercise: competitiveness moderates exercise effort of older adults
This study examined the effect of virtual social facilitation and competitiveness on exercise effort in exergaming older adults. Fourteen exergaming older adults participated. Competitiveness was assessed prior to the start of exercise. Participants were trained to ride a “cybercycle;” a virtual reality-enhanced stationary bike with interactive competition. After establishing a cybercycling baseline, competitive avatars were introduced. Pedaling effort (watts) was assessed. Repeated measures ANOVA revealed a significant group (high vs low competitiveness) × time (pre- to post-avatar) interaction (F[1,12] = 13.1, P = 0.003). Virtual social facilitation increased exercise effort among more competitive exercisers. Exercise programs that match competitiveness may maximize exercise effort
Complement Targets Newborn Retinal Ganglion Cells for Phagocytic Elimination by Microglia
Microglia play important roles in shaping the developing CNS, and at early stages they have been proposed to regulate progenitor proliferation, differentiation, and neuronal survival. However, these studies reveal contradictory outcomes, highlighting the complexity of these cell-cell interactions. Here, we investigate microglia function during embryonic mouse retina development, where only microglia, progenitors, and neurons are present. In both sexes, we determine that microglia primarily interact with retinal neurons and find that depletion of microglia via conditional KO of the Csf1 receptor results in increased density of retinal ganglion cells (RGCs). Pharmacological inhibition of microglia also results in an increase in RGCs, with no effect on retinal progenitor proliferation, RGC genesis, or apoptosis. We show that microglia in the embryonic retina are enriched for phagocytic markers and observe engulfment of nonapoptotic Brn3-labeled RGCs. We investigate the molecular pathways that can mediate cell engulfment by microglia and find selective downregulation of complement pathway components with microglia inhibition, and further show that C1q protein marks a subset of RGCs in the embryonic retina. KO of complement receptor 3 (CR3; Itgam), which is only expressed by microglia, results in increased RGC density, similar to what we observed after depletion or inhibition of microglia. Thus, our data suggest that microglia regulate neuron elimination in the embryonic mouse retina by complement-mediated phagocytosis of non-apoptotic newborn RGCs.
SIGNIFICANCE STATEMENT Microglia are emerging as active and important participants in regulating neuron number in development, during adult neurogenesis, and following stem cell therapies. However, their role in these contexts and the mechanisms involved are not fully defined. Using a well-characterized in vivo system, we provide evidence that microglia regulate neuronal elimination by complement-mediated engulfment of nonapoptotic neurons. This work provides a significant advancement of the field by defining in vivo molecular mechanisms for microglia-mediated cell elimination. Our data add to a growing body of evidence that microglia are essential for proper nervous system development. In addition, we elucidate microglia function in the developing retina, which may shed light on microglia involvement in the context of retinal injury and disease
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Cardiac Biomarkers and Risk of Atrial Fibrillation in Chronic Kidney Disease: The CRIC Study.
Background We tested associations of cardiac biomarkers of myocardial stretch, injury, inflammation, and fibrosis with the risk of incident atrial fibrillation (AF) in a prospective study of chronic kidney disease patients. Methods and Results The study sample was 3053 participants with chronic kidney disease in the multicenter CRIC (Chronic Renal Insufficiency Cohort) study who were not identified as having AF at baseline. Cardiac biomarkers, measured at baseline, were NT-proBNP (N-terminal pro-B-type natriuretic peptide), high-sensitivity troponin T, galectin-3, growth differentiation factor-15, and soluble ST-2. Incident AF ("AF event") was defined as a hospitalization for AF. During a median follow-up of 8 years, 279 (9%) participants developed a new AF event. In adjusted models, higher baseline log-transformed NT-proBNP (N-terminal pro-B-type natriuretic peptide) was associated with incident AF (adjusted hazard ratio [HR] per SD higher concentration: 2.11; 95% CI, 1.75, 2.55), as was log-high-sensitivity troponin T (HR 1.42; 95% CI, 1.20, 1.68). These associations showed a dose-response relationship in categorical analyses. Although log-soluble ST-2 was associated with AF risk in continuous models (HR per SD higher concentration 1.35; 95% CI, 1.16, 1.58), this association was not consistent in categorical analyses. Log-galectin-3 (HR 1.05; 95% CI, 0.91, 1.22) and log-growth differentiation factor-15 (HR 1.16; 95% CI, 0.96, 1.40) were not significantly associated with incident AF. Conclusions We found strong associations between higher NT-proBNP (N-terminal pro-B-type natriuretic peptide) and high-sensitivity troponin T concentrations, and the risk of incident AF in a large cohort of participants with chronic kidney disease. Increased atrial myocardial stretch and myocardial cell injury may be implicated in the high burden of AF in patients with chronic kidney disease
Acute SIV Infection in Sooty Mangabey Monkeys Is Characterized by Rapid Virus Clearance from Lymph Nodes and Absence of Productive Infection in Germinal Centers
Lymphoid tissue immunopathology is a characteristic feature of chronic HIV/SIV infection in AIDS-susceptible species, but is absent in SIV-infected natural hosts. To investigate factors contributing to this difference, we compared germinal center development and SIV RNA distribution in peripheral lymph nodes during primary SIV infection of the natural host sooty mangabey and the non-natural host pig-tailed macaque. Although SIV-infected cells were detected in the lymph node of both species at two weeks post infection, they were confined to the lymph node paracortex in immune-competent mangabeys but were seen in both the paracortex and the germinal center of SIV-infected macaques. By six weeks post infection, SIV-infected cells were no longer detected in the lymph node of sooty mangabeys. The difference in localization and rate of disappearance of SIV-infected cells between the two species was associated with trapping of cell-free virus on follicular dendritic cells and higher numbers of germinal center CD4+ T lymphocytes in macaques post SIV infection. Our data suggests that fundamental differences in the germinal center microenvironment prevent productive SIV infection within the lymph node germinal centers of natural hosts contributing to sustained immune competency
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Research-based versus clinical serum creatinine measurements and the association of acute kidney injury with subsequent kidney function: findings from the Chronic Renal Insufficiency Cohort study.
Background:Observational studies relying on clinically obtained data have shown that acute kidney injury (AKI) is linked to accelerated chronic kidney disease (CKD) progression. However, prior reports lacked uniform collection of important confounders such as proteinuria and pre-AKI kidney function trajectory, and may be susceptible to ascertainment bias, as patients may be more likely to undergo kidney function testing after AKI. Methods:We studied 444 adults with CKD who participated in the prospective Chronic Renal Insufficiency Cohort (CRIC) Study and were concurrent members of a large integrated healthcare delivery system. We estimated glomerular filtration rate (eGFR) trajectories using serum creatinine measurements from (i) the CRIC research protocol (yearly) and (ii) routine clinical care. We used linear mixed effects models to evaluate the associations of AKI with acute absolute change in eGFR and post-AKI eGFR slope, and explored whether these varied by source of creatinine results. Models were adjusted for demographic characteristics, diabetes status and albuminuria. Results:During median follow-up of 8.5 years, mean rate of eGFR loss was -0.31 mL/min/1.73 m2/year overall, and 73 individuals experienced AKI (55% Stage 1). A significant interaction existed between AKI and source of serum creatinine for acute absolute change in eGFR level after discharge; in contrast, AKI was independently associated with a faster rate of eGFR decline (mean additional loss of -0.67 mL/min/1.73 m2/year), which was not impacted by source of serum creatinine. Conclusions:AKI is independently associated with subsequent steeper eGFR decline regardless of the serum creatinine source used, but the strength of association is smaller than observed in prior studies after taking into account key confounders such as pre-AKI eGFR slope and albuminuria
Potential ecological and socio-economic effects of a novel megaherbivore introduction: the hippopotamus in Colombia
Introduced species can have strong ecological, social and economic effects on their non-native environment. Introductions of megafaunal species are rare and may contribute to rewilding efforts, but they may also have pronounced socio-ecological effects because of their scale of influence. A recent introduction of the hippopotamus Hippopotamus amphibius into Colombia is a novel introduction of a megaherbivore onto a new continent, and raises questions about the future dynamics of the socio-ecological system into which it has been introduced. Here we synthesize current knowledge about the Colombian hippopotamus population, review the literature on the species to predict potential ecological and socio-economic effects of this introduction, and make recommendations for future study. Hippopotamuses can have high population growth rates (7–11%) and, on the current trajectory, we predict there could be 400–800 individuals in Colombia by 2050. The hippopotamus is an ecosystem engineer that can have profound effects on terrestrial and aquatic environments and could therefore affect the native biodiversity of the Magdalena River basin. Hippopotamuses are also aggressive and may pose a threat to the many inhabitants of the region who rely upon the Magdalena River for their livelihoods, although the species could provide economic benefits through tourism. Further research is needed to quantify the current and future size and distribution of this hippopotamus population and to predict the likely ecological, social and economic effects. This knowledge must be balanced with consideration of social and cultural concerns to develop appropriate management strategies for this novel introduction
Sp17 Protein Expression and Major Histocompatibility Class I and II Epitope Presentation in Diffuse Large B Cell Lymphoma Patients
Improved therapies are urgently needed for patients with diffuse large B cell lymphoma (DLBCL). Success using immune checkpoint inhibitors and chimeric antigen receptor T cell technology has fuelled demand for validated cancer epitopes. Immunogenic cancer testis antigens (CTAs), with their widespread expression in many tumours but highly restricted normal tissue distribution, represent attractive immunotherapeutic targets that may improve treatment options for DLBCL and other malignancies. Sperm protein 17 (Sp17), a CTA reported to be immunogenic in ovarian cancer and myeloma patients, is expressed in DLBCL. The aim of the present study was to investigate Sp17 epitope presentation via the presence of a cytotoxic T cell (CTL) and a CD4 T-helper (Th) response in DLBCL patients. A significant γ-interferon CTL response was detected in peripheral blood mononuclear cells of 13/31 DLBCL patients following short-term cell stimulation with two novel HLA-A⁎0201 peptides and one previously reported HLA-A⁎0101-restricted nine-mer Sp17 peptide. No significant responses were detected in the HLA-A⁎0201-negative DLBCL patients or four healthy subjects. A novel immunogenic 20-mer CD4 Th Sp17 peptide was detected in 8/17 DLBCL patients. This is the first report of a CTL and a CD4 Th response to Sp17 in DLBCL and supports Sp17 as a potential immunotherapeutic target for DLBCL
Potential ecological and socio-economic effects of a novel megaherbivore introduction: The hippopotamus in Colombia
Introduced species can have strong ecological, social and economic effects on their non-native environment. Introductions of megafaunal species are rare and may contribute to rewilding efforts, but they may also have pronounced socio-ecological effects because of their scale of influence. A recent introduction of the hippopotamus Hippopotamus amphibius into Colombia is a novel introduction of a megaherbivore onto a new continent, and raises questions about the future dynamics of the socio-ecological system into which it has been introduced. Here we synthesize current knowledge about the Colombian hippopotamus population, review the literature on the species to predict potential ecological and socio-economic effects of this introduction, and make recommendations for future study. Hippopotamuses can have high population growth rates (7-11%) and, on the current trajectory, we predict there could be 400-800 individuals in Colombia by 2050. The hippopotamus is an ecosystem engineer that can have profound effects on terrestrial and aquatic environments and could therefore affect the native biodiversity of the Magdalena River basin. Hippopotamuses are also aggressive and may pose a threat to the many inhabitants of the region who rely upon the Magdalena River for their livelihoods, although the species could provide economic benefits through tourism. Further research is needed to quantify the current and future size and distribution of this hippopotamus population and to predict the likely ecological, social and economic effects. This knowledge must be balanced with consideration of social and cultural concerns to develop appropriate management strategies for this novel introduction
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