Pneumococcal surface protein A (PspA) prevents killing of Streptococcus pneumoniae by indolicidin.

Pneumococcal surface protein A (PspA) is an important virulence factor in Streptococcus pneumoniae that binds to lactoferrin and protects the bacterium from the bactericidal action of lactoferricins-cationic peptides released upon lactoferrin proteolysis. The present study investigated if PspA can prevent killing by another cationic peptide, indolicidin. PspA-negative pneumococci were more sensitive to indolicidin-induced killing than bacteria expressing PspA, suggesting that PspA prevents the bactericidal action of indolicidin. Similarly, chemical removal of choline-binding proteins increased sensitivity to indolicidin. The absence of capsule and PspA had an additive effect on pneumococcal killing by the AMP. Furthermore, anti-PspA antibodies enhanced the bactericidal effect of indolicidin on pneumococci, while addition of soluble PspA fragments competitively inhibited indolicidin action. Previous in silico analysis suggests a possible interaction between PspA and indolicidin. Thus, we hypothesize that PspA acts by sequestering indolicidin and preventing it from reaching the bacterial membrane. A specific interaction between PspA and indolicidin was demonstrated by mass spectrometry, confirming that PspA can actively bind to the AMP. These results reinforce the vaccine potential of PspA and suggest a possible mechanism of innate immune evasion employed by pneumococci, which involves binding to cationic peptides and hindering their ability to damage the bacterial membranes.

Progressive heterogeneity of enlarged and irregularly shaped apicoplasts in Plasmodium falciparum persister blood stages after drug treatment.

Morphological modifications and shifts in organelle relationships are hallmarks of dormancy in eukaryotic cells. Communications between altered mitochondria and nuclei are associated with metabolic quiescence of cancer cells that can survive chemotherapy. In plants, changes in the pathways between nuclei, mitochondria, and chloroplasts are associated with cold stress and bud dormancy. Plasmodium falciparum parasites, the deadliest agent of malaria in humans, contain a chloroplast-like organelle (apicoplast) derived from an ancient photosynthetic symbiont. Antimalarial treatments can fail because a fraction of the blood-stage parasites enter dormancy and recrudesce after drug exposure. Altered mitochondrial-nuclear interactions in these persisters have been described for P. falciparum, but interactions of the apicoplast remained to be characterized. In the present study, we examined the apicoplasts of persisters obtained after exposure to dihydroartemisinin (a first-line antimalarial drug) followed by sorbitol treatment, or after exposure to sorbitol treatment alone. As previously observed, the mitochondrion of persisters was consistently enlarged and in close association with the nucleus. In contrast, the apicoplast varied from compact and oblate, like those of active ring-stage parasites, to enlarged and irregularly shaped. Enlarged apicoplasts became more prevalent later in dormancy, but regular size apicoplasts subsequently predominated in actively replicating recrudescent parasites. All three organelles, nucleus, mitochondrion, and apicoplast, became closer during dormancy. Understanding their relationships in erythrocytic-stage persisters may lead to new strategies to prevent recrudescences and protect the future of malaria chemotherapy.

AIBP controls TLR4 inflammarafts and mitochondrial dysfunction in a mouse model of Alzheimer's disease.

Microglia-driven neuroinflammation plays an important role in the development of Alzheimer's disease. Microglia activation is accompanied by the formation and chronic expression of TLR4 inflammarafts, defined as enlarged and cholesterol-rich lipid rafts serving as an assembly platform for TLR4 dimers and complexes of other inflammatory receptors. The secreted apoA-I binding protein (APOA1BP or AIBP) binds TLR4 and selectively targets cholesterol depletion machinery to TLR4 inflammaraft-expressing inflammatory, but not homeostatic microglia. Here we demonstrated that amyloid-beta (Aß) induced formation of TLR4 inflammarafts in microglia in vitro and in the brain of APP/PS1 mice. Mitochondria in Apoa1bp-/- APP/PS1 microglia were hyperbranched and cupped, which was accompanied by increased reactive oxygen species and the dilated endoplasmic reticulum. The size and number of Aß plaques and neuronal cell death were significantly increased, and the animal survival was decreased in Apoa1bp-/-APP/PS1 compared to APP/PS1 female mice. These results suggest that AIBP exerts control of TLR4 inflammarafts and mitochondrial dynamics in microglia and plays a protective role in Alzheimer's disease associated oxidative stress and neurodegeneration.

Racial Differences in Breast Cancer Survival Between Black and White Women According to Tumor Subtype: A Systematic Review and Meta-Analysis.

PURPOSE: Despite effective early-detection approaches and innovative treatments, Black women in the United States have higher breast cancer mortality rates compared with White women. The purpose of this systematic review and meta-analysis is to determine the extent of disparities in breast cancer survival between Black and White women according to tumor subtype. METHODS: A comprehensive database search was performed for full-text, English-language articles published from January 1, 2000, to December 31, 2022. Included studies compared survival between Black and White female patients with breast cancer within subtypes defined by hormone receptor and human epidermal growth factor receptor 2 (HER2)/neu (HER2; now known as ERBB2) status. Random-effects models were used to combine study-specific results and generate pooled relative risks (RRs) and 95% CIs for breast cancer-specific or overall survival (OS). A protocol for this review was registered in PROSPERO (CRD42021268212). RESULTS: Eighteen studies including 228,885 (34,262 Black; 182,466 White) patients with breast cancer were identified. Compared with White women, Black women had a higher risk of breast cancer death for all tumor subtypes. The summary risk of breast cancer death was 50% higher among hormone receptor-positive HER2-negative [HER2-] tumors (RR, 1.50 [95% CI, 1.30 to 1.72]), 34% higher for hormone receptor+/HER2+ (RR, 1.34 [95% CI, 1.10 to 1.64]), 20% higher for hormone receptor-negative (-)/HER2+ (RR, 1.29 [95% CI, 1.00 to 1.43]), and 17% higher among individuals with hormone receptor-/HER2- tumors (hazard ratio, 1.17; 95% CI, 1.10 to 1.25). Black women also had poorer OS than White women for all subtypes. CONCLUSION: These results suggest there are both subtype-specific and subtype-independent mechanisms that contribute to disparities in breast cancer survival between Black and White women, which require multilevel interventions to address and achieve health equity.

Journal of Women's Health Clinical Update.

The Clinical Update series is intended to help busy clinicians stay up-to-date with recently published important and potentially practice-changing articles on topics pertinent to the care of women. In this update on sexual health, we review studies on the sexual health content of healthcare professional curricula, sexual health and intimacy after cancer in women of color, sexual function in women with polycystic ovarian syndrome, as well as the risks associated with the use of testosterone in women.

Differences in standing behavior between Jersey and Holstein dairy cows during the periparturient period.

Jerseys are the second most popular breed in the US dairy industry, yet there are few studies that directly compare their behavior with Holsteins. The objective of this observational study was to describe differences in the standing behavior of healthy Jersey and Holstein dairy cows during the periparturient period. A total of 51 Jerseys (11 primiparous [PP] and 40 multiparous [MP]) and 36 Holsteins (8 PP, 28 MP) were used for this analysis. Data loggers that measured leg orientation were used to determine daily standing time (min/d), number of standing bouts (no./d), and standing bout duration for each cow from approximately 3 wk before until 4 wk after calving. Holstein and Jersey cows were commingled throughout the periparturient period and only healthy cows were included in the analysis. Overall, Jerseys had longer standing times and longer standing bout durations compared with Holsteins during the period before calving. On the day before calving, PP cows had longer standing times than MP cows, but there was no effect of breed on standing behavior during the calving period (d -1, 0, and +1 relative to calving). The number of standing bouts for all cows spiked on the day of calving, but this increase was greatest for the MP cows, regardless of breed. Primiparous cows had longer postpartum standing times compared with MP cows; however, PP Jerseys tended to have the longest daily standing times during the first 10 DIM. After calving, there were no breed differences in the number of standing bouts per day among MP cows; however, PP Jerseys had more standing bouts than PP Holsteins during this time. Understanding how Jersey and Holstein behaviors differ may offer insights into better management of Jerseys during the period around calving.

Impact of Skin Care Products on Phthalates and Phthalate Replacements in Children: the ECHO-FGS.

BACKGROUND: Phthalates and their replacements have been implicated as developmental toxicants. Young children may be exposed to phthalates/replacements when using skin care products (SCPs). OBJECTIVES: Our objective is to assess the associations between use of SCPs and children's urinary phthalate/replacement metabolite concentrations. METHODS: Children (4-8 years old) from the Environmental Influences on Child Health Outcomes-Fetal Growth Study (ECHO-FGS) cohort provided spot urine samples from 2017 to 2019, and mothers were queried about children's SCP use in the past 24 h (n=906). Concentrations of 16 urinary phthalate/replacement metabolites were determined by liquid chromatography-tandem mass spectrometry (n=630). We used linear regression to estimate the child's use of different SCPs as individual predictors of urinary phthalate/replacement metabolites, adjusted for urinary specific gravity, age, sex assigned at birth, body mass index, and self-reported race/ethnic identity, as well as maternal education, and season of specimen collection. We created self-organizing maps (SOM) to group children into "exposure profiles" that reflect discovered patterns of use for multiple SCPs. RESULTS: Children had lotions applied (43.0%) frequently, but "2-in-1" hair-care products (7.5%), sunscreens (5.9%), and oils (4.3%) infrequently. Use of lotions was associated with 1.17-fold [95% confidence interval (CI): 1.00, 1.34] greater mono-benzyl phthalate and oils with 2.86-fold (95% CI: 1.89, 4.31) greater monoethyl phthalate (MEP), 1.43-fold (95% CI: 1.09, 1.90) greater monobutyl phthalate (MBP), and 1.40-fold (95% CI: 1.22, 1.61) greater low-molecular-weight phthalates (LMW). Use of 2-in-1 haircare products was associated with 0.84-fold (95% CI: 0.72, 0.97) and 0.78-fold (95% CI: 0.62, 0.98) lesser mono(3-carboxypropyl) phthalate (MCPP) and MBP, respectively. Child's race/ethnic identity modified the associations of lotions with LMW, oils with MEP and LMW, sunscreen with MCPP, ointments with MEP, and hair conditioner with MCPP. SOM identified four distinct SCP-use exposure scenarios (i.e., profiles) within our population that predicted 1.09-fold (95% CI: 1.03, 1.15) greater mono-carboxy isononyl phthalate, 1.31-fold (95% CI: 0.98, 1.77) greater mono-2-ethyl-5-hydroxyhexyl terephthalate, 1.13-fold (95% CI: 0.99, 1.29) greater monoethylhexyl phthalate, and 1.04-fold (95% CI: 1.00, 1.09) greater diethylhexyl phthalate. DISCUSSION: We found that reported SCP use was associated with urinary phthalate/replacement metabolites in young children. These results may inform policymakers, clinicians, and parents to help limit children's exposure to developmental toxicants. https://doi.org/10.1289/EHP13937.

Single-cell analyses of polyclonal Plasmodium vivax infections and their consequences on parasite transmission.

Most Plasmodium vivax infections contain genetically distinct parasites, but the consequences of this polyclonality on the development of asexual parasites, their sexual differentiation, and their transmission remain unknown. We describe infections of Saimiri monkeys with two strains of P. vivax and the analyses of 80,024 parasites characterized by single cell RNA sequencing and individually genotyped. In our model, consecutive inoculations fail to establish polyclonal infections. By contrast, simultaneous inoculations of two strains lead to sustained polyclonal infections, although without detectable differences in parasite regulation or sexual commitment. Analyses of sporozoites dissected from mosquitoes fed on coinfected monkeys show that all genotypes are successfully transmitted to mosquitoes. However, after sporozoite inoculation, not all genotypes contribute to the subsequent blood infections, highlighting an important bottleneck during pre-erythrocytic development. Overall, these studies provide new insights on the mechanisms regulating the establishment of polyclonal P. vivax infections and their consequences for disease transmission.

Association of race/ethnicity and insurance with survival in patients with diffuse large B-cell lymphoma in a large real-world cohort.

The large real-world EHR dataset Flatiron has shown that race was not significantly associated with poorer survival in patients with DLBCL. Medicaid insurance status was significantly associated with poorer overall survival and time to second-line therapy or death due to any cause in patients with DLBCL aged <65 years.

OBJECTIVE: Few studies have evaluated disparities in race, ethnicity, and health insurance in real­world health outcomes for patients with diffuse large B­cell lymphoma (DLBCL). This study aimed to evaluate association between racial disparities and health insurance with real­world health outcomes. METHODS: Patients with DLBCL (January 2011­July 2021) treated with first­line therapy were selected from a real­world database. Variables of interest included race/ethnicity, health insurance type (Medicaid, Commercial) by patient age (<65, ≥65 years), stage at diagnosis, overall survival (OS), and time to second­line therapy or death due to any cause (TTNTD). RESULTS: Among 5362 patients with DLBCL (82% White, 7% Black, 8% Hispanic/Latino, 3% Asian), White patients were older (mean age, 66.7 vs. 59.3­62.5 years) and less likely to have Medicaid insurance (1.7% vs. 3.4%­5.9%). Adjusted hazard ratios (aHR) for OS (Black, 0.88 [95% confidence interval, 0.72­1.07]; Hispanic/Latino, 0.84 [0.70­1.03]; Asian, 0.82 [0.59­1.16]) and TTNTD (Black, 0.89 [0.75­1.05]; Hispanic/Latino, 0.85 [0.73­1.00]; Asian, 1.11 [0.86­1.43]) were similar to those of White patients. Among patients aged <65 years, Medicaid­insured versus Commercially insured patients had more advanced disease (stage III­IV, 66% vs. 48%), worse OS (aHR, 0.52 [0.34­0.80]; p = 0.003), and shorter TTNTD (aHR, 0.70 [0.49­0.99]; p = 0.044). CONCLUSIONS: There was no statistically significant difference in these variables/outcomes between Medicaid­insured and commercially insured patients aged ≥65 years. Medicaid­insured status was significantly associated with poorer OS and TTNTD in patients with DLBCL aged <65 years but not in those aged ≥65 years, with or without adjusting for other baseline characteristics. Race was not significantly associated with these outcomes.

Disseminated paracoccidioidomycosis in a captive western black-handed tamarin (Saguinus niger).

Paracoccidioidomycosis (PCM) is an endemic fungal disease that occurs in Latin America and primarily affects humans. The disease has been rarely documented in non-human primates. This report details a disseminated and fatal case of PCM caused by Paracoccidioides brasiliensis in a western black-handed tamarin (Saguinus niger) under human care. Histopathological examination revealed extensive pyogranulomatous inflammation in the lungs, spleen, liver, lymph nodes, kidneys, epididymis, right testicle, heart, adrenal gland and intestines, associated with characteristic yeast forms consistent with Paracoccidioides spp and confirmed by immunohistochemistry. Molecular analysis indicated a high nucleotide similarity with P. brasiliensis sequences for both the 18S rRNA and gp43 genes. This naturally occurring infection highlights the susceptibility of these animals to PCM and their role in ecoepidemiology warrants further investigation.

Phosphodiesterase-4 Inhibitors Increase Pigment Cell Proliferation and Melanization in Cultured Melanocytes and within a 3-Dimensional Skin Equivalent Model.

Vitiligo is a common chronic autoimmune disease characterized by white macules and patches of the skin, having a negative impact on patients' life and without any definitive cure at present. Identification of new compounds to reverse depigmentation is therefore a pressing need for this disease. The pharmacologic compounds phosphodiesterase-4 inhibitors (PDE4is) are small molecules with immunomodulatory properties used for treatment of inflammatory dermatoses. PDE4is have shown repigmentation effects in patients with vitiligo, in some case reports. We characterized the proliferative and melanogenic potential of 2 known PDE4is-crisaborole and roflumilast-and of a more recently designed compound, PF-07038124. We used 2 in vitro model systems-the primary human melanocyte culture and a 3-dimensional cocultured skin model (MelanoDerm)-with an exploratory testing platform composed of complementary assays (spectrophotometry, melanin and proliferation assays, immunostaining, Fontana-Masson staining, RT-qPCR, western blot, and whole-transcriptome RNA sequencing). We identified that treatment with PDE4is was associated with increased melanocyte proliferation and melanization in both in vitro models and with increase in the melanogenic genes and proteins expression in cultured melanocytes. These effects were found to be enhanced by addition of α-melanocyte-stimulating hormone. Our findings support the further evaluation of PDE4is with or without α-melanocyte-stimulating hormone agonists in vitiligo trials.

Evaluating the before operational stress program: comparing in-person and virtual delivery.

Introduction: Public safety personnel (PSP) are at increased risk for posttraumatic stress injuries (PTSI). Before Operational Stress (BOS) is a mental health program for PSP with preliminary support mitigating PTSI. The current study compared the effectiveness of delivering BOS in-person by a registered clinician (i.e., Intensive) to virtually delivery by a trained clinician (i.e., Classroom). Methods: Canadian PSP completed the Intensive (n = 118; 61.9% male) or Classroom (n = 149; 50.3% male) program, with self-report surveys at pre-, post-, 1 month, and 4 months follow-ups. Results: Multilevel modelling evidenced comparable reductions in anxiety (p < 0.05, ES = 0.21) and emotional regulation difficulties (ps < 0.05, ESs = 0.20, 0.25) over time with no significant difference between modalities. Participants discussed benefits of the delivery modality they received. Discussion: The results support virtual delivery of the BOS program (Classroom) as an accessible mental health training option for PSP, producing effects comparable to in-person delivery by clinicians.

VISTA Emerges as a Promising Target against Immune Evasion Mechanisms in Medulloblastoma.

BACKGROUND: Relapsed medulloblastoma (MB) poses a significant therapeutic challenge due to its highly immunosuppressive tumor microenvironment. Immune checkpoint inhibitors (ICIs) have struggled to mitigate this challenge, largely due to low T-cell infiltration and minimal PD-L1 expression. Identifying the mechanisms driving low T-cell infiltration is crucial for developing more effective immunotherapies. METHODS: We utilize a syngeneic mouse model to investigate the tumor immune microenvironment of MB and compare our findings to transcriptomic and proteomic data from human MB. RESULTS: Flow cytometry reveals a notable presence of CD45hi/CD11bhi macrophage-like and CD45int/CD11bint microglia-like tumor-associated macrophages (TAMs), alongside regulatory T-cells (Tregs), expressing high levels of the inhibitory checkpoint molecule VISTA. Compared to sham control mice, the CD45hi/CD11bhi compartment significantly expands in tumor-bearing mice and exhibits a myeloid-specific signature composed of VISTA, CD80, PD-L1, CTLA-4, MHCII, CD40, and CD68. These findings are corroborated by proteomic and transcriptomic analyses of human MB samples. Immunohistochemistry highlights an abundance of VISTA-expressing myeloid cells clustering at the tumor-cerebellar border, while T-cells are scarce and express FOXP3. Additionally, tumor cells exhibit immunosuppressive properties, inhibiting CD4 T-cell proliferation in vitro. Identification of VISTA's binding partner, VSIG8, on tumor cells, and its correlation with increased VISTA expression in human transcriptomic analyses suggests a potential therapeutic target. CONCLUSIONS: This study underscores the multifaceted mechanisms of immune evasion in MB and highlights the therapeutic potential of targeting the VISTA-VSIG axis to enhance anti-tumor responses.

Shifts in the gut microbiota of sea urchin Diadema antillarum associated with the 2022 disease outbreak.

Introduction: In recent decades, Caribbean coral reefs have lost many vital marine species due to diseases. The well-documented mass mortality event of the long-spined black sea urchin Diadema antillarum in the early 1980s stands out among these collapses. This die-off killed over 90% of D. antillarum changing the reefscape from coral to algal-dominated. Nearly 40 years later, D. antillarum populations have yet to recover. In early 2022, a new mortality event of D. antillarum was reported along the Caribbean, including Puerto Rico. Methods: This study identifies the gut microbiota changes associated with the D. antillarum during this mortality event. It contrasts them with the bacterial composition of gut samples from healthy individuals collected in 2019 by using 16S rRNA sequencing analyses. Results: Notably, the die-off group's core microbiome resembled bacteria commonly found in the human skin and gut, suggesting potential anthropogenic contamination and wastewater pollution as contributing factors to the 2022 dysbiosis. The animals collected in 2022, especially those with signs of disease, lacked keystone taxa normally found in Diadema including Photobacterium and Propionigenium. Discussion: The association between human microbes and disease stages in the long-spined urchin D. antillarum, especially in relation to anthropogenic contamination, highlights a complex interplay between environmental stressors and marine health. While these microbes might not be the direct cause of death in this species of sea urchins, their presence and proliferation can indicate underlying issues, such as immune depletion due to pollution, habitat destruction, or climate change, that ultimately compromise the health of these marine organisms.

Substrate-induced strain in molybdenum disulfide grown by aerosol-assisted chemical vapor deposition.

Transition metal dichalcogenides have been extensively studied in recent years because of their fascinating optical, electrical, and catalytic properties. However, low-cost, scalable production remains a challenge. Aerosol-assisted chemical vapor deposition (AACVD) provides a new method for scalable thin film growth. In this study, we demonstrate the growth of molybdenum disulfide (MoS2) thin films using AACVD method. This method proves its suitability for low-temperature growth of MoS2thin films on various substrates, such as glass, silicon dioxide, quartz, silicon, hexagonal boron nitride, and highly ordered pyrolytic graphite. The as-grown MoS2shows evidence of substrate-induced strain. The type of strain and the morphology of the as-grown MoS2highly depend on the growth substrate's surface roughness, crystallinity, and chemical reactivity. Moreover, the as-grown MoS2shows the presence of both direct and indirect band gaps, suitable for exploitation in future electronics and optoelectronics.

Concepts and Approaches in the Management of Transgender and Gender-Diverse Patients.

The terms transgender and gender diverse (TGD) describe persons whose gender is different from the sex assigned to them at birth. While TGD persons have experienced a rise in cultural and social visibility in recent decades, they continue to experience significant health inequities, including adverse health outcomes and multiple barriers to accessing medical care. Transgender and gender-diverse persons are at a higher risk for pain conditions than their cisgender counterparts, but research on chronic pain management for TGD persons is lacking. Clinicians from all disciplines must be informed of best practices for managing chronic pain in the TGD population. This includes all aspects of care including history, physical examination, diagnosis, treatment, and perioperative management. Many TGD persons report delaying or avoiding care because of negative interactions with medical practitioners who do not have sufficient training in navigating the specific health care needs of TGD patients. Furthermore, TGD persons who do seek care are often forced to educate their practitioners on their specific health care needs. This paper provides an overview of existing knowledge and recommendations for physicians to provide culturally and medically appropriate care for TGD persons.

Management of the Vasomotor Symptoms of Menopause: Twofers in Your Clinical Toolbox.

The number of midlife women transitioning into menopause is substantial, with more than 1 million women in the United States entering menopause each year. Vasomotor symptoms (VMS), mood and sleep disturbances, and sexual problems are common during the menopause transition yet often go untreated. Menopausal hormone therapy is the most effective treatment of VMS, and the benefits typically outweigh the risks for women without contraindications who are younger than 60 years or within 10 years from menopause onset. For women who cannot or choose not to use hormone therapy, nonhormone prescription options exist to treat VMS. Many of these therapies have secondary benefits beyond VMS relief. For example, whereas paroxetine is Food and Drug Administration approved to treat VMS, it can also help with depressive and anxiety symptoms. The aim of this paper is to summarize prescription treatments of VMS and their secondary benefits for other common symptoms experienced by midlife women. The tools presented will help clinicians caring for midlife women provide individualized, comprehensive care with the goal of improving their quality of life during the menopause transition and beyond.

Infectivity of Plasmodium parasites to Aedes aegypti and Anopheles stephensi mosquitoes maintained on blood-free meals of SkitoSnack.

BACKGROUND: Aedes and Anopheles mosquitoes are responsible for tremendous global health burdens from their transmission of pathogens causing malaria, lymphatic filariasis, dengue, and yellow fever. Innovative vector control strategies will help to reduce the prevalence of these diseases. Mass rearing of mosquitoes for research and support of these strategies presently depends on meals of vertebrate blood, which is subject to acquisition, handling, and storage issues. Various blood-free replacements have been formulated for these mosquitoes, but none of these replacements are in wide use, and little is known about their potential impact on competence of the mosquitoes for Plasmodium infection. METHODS: Colonies of Aedes aegypti and Anopheles stephensi were continuously maintained on a blood-free replacement (SkitoSnack; SS) or bovine blood (BB) and monitored for engorgement and hatch rates. Infections of Ae. aegypti and An. stephensi were assessed with Plasmodium gallinaceum and P. falciparum, respectively. RESULTS: Replicate colonies of mosquitoes were maintained on BB or SS for 10 generations of Ae. aegypti and more than 63 generations of An. stephensi. The odds of engorgement by SS- relative to BB-maintained mosquitoes were higher for both Ae. aegypti (OR = 2.6, 95% CI 1.3-5.2) and An. stephensi (OR 2.7, 95% CI 1.4-5.5), while lower odds of hatching were found for eggs from the SS-maintained mosquitoes of both species (Ae. aegypti OR = 0.40, 95% CI 0.26-0.62; An. stephensi OR = 0.59, 95% CI 0.36-0.96). Oocyst counts were similar for P. gallinaceum infections of Ae. aegypti mosquitoes maintained on SS or BB (mean ratio = [mean on SS]/[mean on BB] = 1.11, 95% CI 0.85-1.49). Similar oocyst counts were also observed from the P. falciparum infections of SS- or BB-maintained An. stephensi (mean ratio = 0.76, 95% CI 0.44-1.37). The average counts of sporozoites/mosquito showed no evidence of reductions in the SS-maintained relative to BB-maintained mosquitoes of both species. CONCLUSIONS: Aedes aegypti and An. stephensi can be reliably maintained on SS over multiple generations and are as competent for Plasmodium infection as mosquitoes maintained on BB. Use of SS alleviates the need to acquire and preserve blood for mosquito husbandry and may support new initiatives in fundamental and applied research, including novel manipulations of midgut microbiota and factors important to the mosquito life cycle and pathogen susceptibility.

Sexual victimization among Royal Canadian Mounted Police.

OBJECTIVE: The present study was designed to provide the first in-depth, academically peer-reviewed assessment of sexual victimization among Royal Canadian Mounted Police (RCMP). METHOD: A representative sample of RCMP (n = 1,324; 76.5% men) completed the self-report survey. RESULTS: Participants reported a higher overall lifetime history of sexual assault than would be expected for the general population (p < .05). Women participants reported a higher prevalence of lifetime history of sexual assault (p < .05). Participants reported being sexually assaulted during the RCMP Cadet Training Program (CTP; n = 27), with comparable proportions of men and women. Participants reported being sexually assaulted while on duty (n = 168), with a greater proportion of women reporting being sexually assaulted than men (p < .05). Women more often reported being sexually assaulted while on duty by a superior, coworker or peer, or subordinate, whereas men more often reported being sexually assaulted by a civilian. Participants (n = 94) reported being sexually harassed during the CTP and while on duty (n = 282), with a greater proportion of women reporting being sexually harassed during the CTP and while on duty. CONCLUSIONS: RCMP cadets appear to be sexually assaulted and sexually harassed less frequently than Canadian university and military college students, whereas RCMP appear to be sexually assaulted more often while on duty than Canadian men and women in the general population while at work; however, direct comparisons are problematic because of differing frames for questions and time spans. The current results help quantify sexual victimization among RCMP, which can support ongoing and novel prevention and intervention strategies. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Synthesis and activity of benzimidazole N-Acylhydrazones against Trypanosoma cruzi, Leishmania amazonensis and Leishmania infantum.

In this study, we present the design, synthesis, and cytotoxic evaluation of a series of benzimidazole N-acylhydrazones against strains of T. cruzi (Y and Tulahuen) and Leishmania species (L. amazonensis and L. infantum). Compound (E)-N'-((5-Nitrofuran-2-yl)methylene)-1H-benzo[d]imidazole-2-carbohydrazide demonstrated significant activity against both trypomastigote and amastigote forms (Tulahuen strain), with an IC50/120 h of 0.033 µM and a selectivity index (SI) of 7680. This represents a potency 46 times greater than that of benznidazole (IC50/120 h = 1.520 µM, SI = 1390). Another compound (E)-N'-(2-Hydroxybenzylidene)-1H-benzo[d]imidazole-2-carbohydrazide showed promising activity against both trypomastigote and amastigote forms (Tulahuen strain), with an IC50/120 h of 3.600 µM and an SI of 14.70. However, its efficacy against L. infantum and L. amazonensis was comparatively lower. These findings provide valuable insights for the development of more effective treatments against Trypanosoma cruzi.