A PIKfyve modulator combined with an integrated stress response inhibitor to treat lysosomal storage diseases.

Lysosomal degradation pathways coordinate the clearance of superfluous and damaged cellular components. Compromised lysosomal degradation is a hallmark of many degenerative diseases, including lysosomal storage diseases (LSDs), which are caused by loss-of-function mutations within both alleles of a lysosomal hydrolase, leading to lysosomal substrate accumulation. Gaucher's disease, characterized by <15% of normal glucocerebrosidase function, is the most common LSD and is a prominent risk factor for developing Parkinson's disease. Here, we show that either of two structurally distinct small molecules that modulate PIKfyve activity, identified in a high-throughput cellular lipid droplet clearance screen, can improve glucocerebrosidase function in Gaucher patient-derived fibroblasts through an MiT/TFE transcription factor that promotes lysosomal gene translation. An integrated stress response (ISR) antagonist used in combination with a PIKfyve modulator further improves cellular glucocerebrosidase activity, likely because ISR signaling appears to also be slightly activated by treatment by either small molecule at the higher doses employed. This strategy of combining a PIKfyve modulator with an ISR inhibitor improves mutant lysosomal hydrolase function in cellular models of additional LSD.

"That's My Girl; I love her": The Promise of Compassionate, Inclusive Healthcare for Black Transgender Women to Support PrEP Use.

There are significant disparities in HIV pre-exposure prophylaxis (PrEP) use that disproportionately impact Black transgender women. Medical mistrust and discriminatory experiences in healthcare settings have been identified as critical barriers to equitable PrEP implementation. This qualitative study examines Black transgender women's experiences in healthcare to better understand how patient-provider relationships can help overcome the challenges brought on by medical mistrust. We interviewed 42 Black transgender women about their experiences with healthcare and PrEP access. Data were analyzed using inductive thematic content analysis to develop the following themes: (1) historical and ongoing marginalization and exclusion from healthcare remains a barrier to PrEP use; (2) Many providers continue to be unprepared to prescribe PrEP; (3) Providers can act as important advocates and sources of support; and (4) Compassionate, trusting patient-provider relationships can facilitate PrEP use. Our results highlight the importance of supportive and positive patient-provider relationships and demonstrate how providers can build trusting relationships with Black transgender women to help overcome barriers to healthcare and PrEP use.

Stigma, serostatus disclosure, coping strategies, and the role of social capital resources among HIV care-nonadherent MSM in Russia: a qualitative analysis.

The HIV epidemic continues to expand in Russia, with suboptimal levels of care uptake. This qualitative study aimed to characterize social capital resources and lived stigma experiences, coping, and disclosure among care-nonadherent men who have sex with men (MSM) living with HIV in Russia. Twenty-five HIV-positive MSM - recruited online - completed in-depth interviews over Zoom, with data analyzed using MAXQDA software. Stigma was more likely to be encountered in interactions with persons with whom social ties were weaker such as medical providers and relatives, particularly males. Close friends - often other HIV-positive MSM and female relatives - were the most supportive and least stigmatizing. Similar persons were most often considered for HIV serostatus disclosure. Coping strategies to reduce the impact of stigma included ignoring stigmatizing experiences, seeking support from members of one's social circle, minimizing contact with stigmatizing persons, seeking new relationships with persons who are also HIV-positive, proactively reducing stigma through involvement in advocacy roles, and correcting myths and educating others about HIV infection. These findings underscore the need for interventions to assist HIV-positive MSM in building accepting social capital resources to reduce the impact of stigma and to build support within their social networks, often with other HIV-positive MSM.

Factors associated with PrEP use in a community sample of African American men who have sex with men (MSM) and transgender women (TGW) in the United States Midwest.

Black sexual minority men who have sex with men (MSM) in the United States are at disparate risk for contracting HIV infection, but pre-exposure prophylaxis (PrEP) use is suboptimal. Social network methods were used to recruit a community sample of racial minority MSM and transgender women (TGW) in two Midwestern US cities. 250 PrEP-eligible (HIV-negative) participants completed measures assessing current and intended PrEP use; demographic characteristics; PrEP knowledge, attitudes, norms, stigma, and self-efficacy; and structural barriers to PrEP. Multivariate analyses established predictors of current and intended PrEP use. Only 12% of participants reported currently using PrEP, which was associated with greater PrEP knowledge and not having a main partner, with trends for greater PrEP use by younger participants and those with partners living with HIV. Among participants not currently on PrEP, strength of PrEP use intentions was associated with higher PrEP knowledge, PrEP descriptive social norms, and PrEP use self-efficacy. This study is among few to directly compare Black who have adopted PrEP with those who have not. Its findings underscore the potential benefits of employing social network approaches for strengthening PrEP use peer norms, increasing PrEP knowledge and self-efficacy, and optimizing PrEP uptake among racial minority MSM and TGW.

Quantifying long-term phenological patterns of aerial insectivores roosting in the Great Lakes region using weather surveillance radar.

Organisms have been shifting their timing of life history events (phenology) in response to changes in the emergence of resources induced by climate change. Yet understanding these patterns at large scales and across long time series is often challenging. Here we used the US weather surveillance radar network to collect data on the timing of communal swallow and martin roosts and evaluate the scale of phenological shifts and its potential association with temperature. The discrete morning departures of these aggregated aerial insectivores from ground-based roosting locations are detected by radars around sunrise. For the first time, we applied a machine learning algorithm to automatically detect and track these large-scale behaviors. We used 21 years of data from 12 weather surveillance radar stations in the Great Lakes region to quantify the phenology in roosting behavior of aerial insectivores at three spatial levels: local roost cluster, radar station, and across the Great Lakes region. We show that their peak roosting activity timing has advanced by 2.26 days per decade at the regional scale. Similar signals of advancement were found at the station scale, but not at the local roost cluster scale. Air temperature trends in the Great Lakes region during the active roosting period were predictive of later stages of roosting phenology trends (75% and 90% passage dates). Our study represents one of the longest-term broad-scale phenology examinations of avian aerial insectivore species responding to environmental change and provides a stepping stone for examining potential phenological mismatches across trophic levels at broad spatial scales.

Declines in an abundant aquatic insect, the burrowing mayfly, across major North American waterways.

Seasonal animal movement among disparate habitats is a fundamental mechanism by which energy, nutrients, and biomass are transported across ecotones. A dramatic example of such exchange is the annual emergence of mayfly swarms from freshwater benthic habitats, but their characterization at macroscales has remained impossible. We analyzed radar observations of mayfly emergence flights to quantify long-term changes in annual biomass transport along the Upper Mississippi River and Western Lake Erie Basin. A single emergence event can produce 87.9 billion mayflies, releasing 3,078.6 tons of biomass into the airspace over several hours, but in recent years, production across both waterways has declined by over 50%. As a primary prey source in aquatic and terrestrial ecosystems, these declines will impact higher trophic levels and environmental nutrient cycling.

Intersectional Resilience Among Black Gay, Bisexual, and Other Men Who Have Sex With Men, Wisconsin and Ohio, 2019.

Objectives. To investigate resilience strategies used by Black gay, bisexual, and other men who have sex with men (MSM) to navigate racism and heterosexism. Methods. In 2019, we conducted in-depth interviews with 46 Black MSM in Milwaukee, Wisconsin, and Cleveland, Ohio. Thematic analysis, informed by intersectionality, was used to identify intersectional resilience within the context of participants' lives. Results. Our analyses revealed ways in which Black MSM respond to stigma and oppression. We identified the following themes that capture these experiences: pride in intersectional identities, perseverance, community advocacy, and social support. Our analyses reveal how men draw on these assets and resources to positively adapt despite experiences of racism and heterosexism. Conclusions. Intersectional resilience can support Black MSM in navigating racism and heterosexism. However, public health interventions at the institutional and system levels are needed to directly target the root causes of oppression and support resources that facilitate intersectional resilience. (Am J Public Health. 2022;112(S4):S405-S412. https://doi.org/10.2105/AJPH.2021.306677).

Nocturnal city lighting elicits a macroscale response from an insect outbreak population.

Anthropogenic environmental change affects organisms by exposing them to enhanced sensory stimuli that can elicit novel behavioural responses. A pervasive feature of the built environment is artificial nocturnal lighting, and brightly lit urban areas can influence organism abundance, distribution and community structure within proximate landscapes. In some cases, the attractive or disorienting effect of artificial light at night can draw animals into highly unfavourable habitats, acting as a macroscale attractive ecological sink. Despite their significance for animal ecology, identifying cases of these phenomena and determining their effective scales and the number of organisms impacted remains challenging. Using an integrated set of remote-sensing observations, we quantify the effect of a large-scale attractive sink on nocturnal flights of an outbreak insect population in Las Vegas, USA. At the peak of the outbreak, over 45 million grasshoppers took flight across the region, with the greatest numbers concentrating over high-intensity city lighting. Patterns of dusk ascent from vegetated habitat toward urban areas suggest a daily pull toward a time-varying nocturnal attractive sink. The strength of this attractor varies with grasshopper density. These observations provide the first macroscale characterization of the effects of nocturnal urban lighting on the behaviour of regional insect populations and demonstrate the link between insect perception of the built environment and resulting changes in spatial and movement ecology. As human-induced environmental change continues to affect insect populations, understanding the impacts of nocturnal light on insect behaviour and fitness will be vital to developing robust large-scale management and conservation strategies.

Social network intervention to increase pre-exposure prophylaxis (PrEP) awareness, interest, and use among African American men who have sex with men.

In the U.S., HIV incidence is highest among Black men who have sex with men (MSM) but PrEP uptake is low, in part due to lack of normative support for using PrEP. This research pilot tested a social network-level intervention designed to increase PrEP use willingness, interest, and peer supports among Black MSM in Milwaukee. Five community social networks (n = 40 participants) of racial minority MSM were assessed at baseline with measures of PrEP knowledge, interest, attitudes, and action taking. Persons most interconnected with others in each network attended an intervention that provided training to increase knowledge about PrEPbenefits, address PrEP concerns, endorse PrEP use as a symbol of pride and health, and deliver these messages to others in their social networks. All network members were re-administered the same measures at 3-month followup. Significant increases over time were found in network members' PrEP knowledge, attitudes, norm perceptions, self-efficacy, and willingness to use PrEP. Participants more often talked with friends about HIV and with their health care providers about PrEP. The percentage of participants who reported using PrEP increased from 3% to 11%. Larger-scale evaluations of this intervention model are needed.

Mobilizing individual social capital resources for HIV care support: results of a pilot intervention in St. Petersburg, Russia.

Half of HIV-positive persons in Russia are on antiretroviral therapy (ART), and only 27% are virally suppressed. A feasibility pilot intervention to mobilize social capital resources for HIV care support was conducted in St. Petersburg. Out-of-care or ART-nonadherent HIV-positive persons (n = 24) attended a five-session intervention to increase access social capital resources (i.e., family, friends, or providers) to mobilize supports for entering care, initiating care, and adhering to ART. HIV care indicators were assessed at baseline, an immediate followup (FU-1), and 6-month followup (FU-2) points. At FU-1, participants more frequently discussed their care experiences with others, verifying the intervention's mechanism of action. Participants increased in scales of medication taking adherence (p = 0.002, FU-1; p = 0.011, FU-2), self-efficacy (p = 0.042; FU-1), and outcome expectancies (p = 0.016, FU-2). Among persons not on ART, HIV Medication Readiness scale scores increased at FU-1 (p = 0.032) but became attenuated at FU-2. Participants tended to more frequently keep care appointments (79%, baseline to 90%, FU-1, p = 0.077); to have undetectable viral load (54%, baseline to 74%, FU-2; p = 0.063); and to have fewer past-month days with delayed or incomplete medication doses (7.8, baseline to 4.2, FU-1; p = 0.084). This novel social capital intervention is promising for improving HIV care-related outcomes and warrants a full-scale evaluation.

The Influence of Peers on PrEP Perceptions and Use Among Young Black Gay, Bisexual, and Other Men Who Have Sex with Men: A Qualitative Examination.

Pre-exposure prophylaxis (PrEP) is a promising part of HIV prevention, yet racial disparities in PrEP uptake persist. Evidence indicates that Black gay, bisexual, and other men who have sex with men (GBM) face numerous social and structural barriers to PrEP, including stigma, medical mistrust, and exclusion from the healthcare system. However, little research has examined how social networks can influence PrEP use and help Black GBM overcome these identified barriers. To understand the influence of peers and social networks on Black GBM's perceptions of and decisions about PrEP use, we conducted in-depth interviews with 46 Black GBM in Milwaukee, WI and Cleveland, OH. Data were analyzed using multistage inductive coding and thematic content analysis, using MAXQDA software. Results indicate that participants' primary source of information on PrEP was other Black GBM in their communities. Peers and social networks served three primary functions with regard to PrEP: (1) filling informational gaps left by healthcare providers, (2) increasing trust of PrEP, and (3) reducing PrEP stigma. Participants described the "movers and shakers" in Black LGBT communities who have been influential in educating others and advocating for PrEP. Well-respected vocal advocates for PrEP have emerged in the Black LGBT community as PrEP champions who have successfully influenced young Black GBM's views on PrEP. Our results reveal the role social networks and peer groups can play in increasing PrEP use among Black GBM. Social network interventions may help overcome the stigma and mistrust that are contributing to PrEP disparities.

Holding steady: Little change in intensity or timing of bird migration over the Gulf of Mexico.

Quantifying the timing and intensity of migratory movements is imperative for understanding impacts of changing landscapes and climates on migratory bird populations. Billions of birds migrate in the Western Hemisphere, but accurately estimating the population size of one migratory species, let alone hundreds, presents numerous obstacles. Here, we quantify the timing, intensity, and distribution of bird migration through one of the largest migration corridors in the Western Hemisphere, the Gulf of Mexico (the Gulf). We further assess whether there have been changes in migration timing or intensity through the Gulf. To achieve this, we integrate citizen science (eBird) observations with 21 years of weather surveillance radar data (1995-2015). We predicted no change in migration timing and a decline in migration intensity across the time series. We estimate that an average of 2.1 billion birds pass through this region each spring en route to Nearctic breeding grounds. Annually, half of these individuals pass through the region in just 18 days, between April 19 and May 7. The western region of the Gulf showed a mean rate of passage 5.4 times higher than the central and eastern regions. We did not detect an overall change in the annual numbers of migrants (2007-2015) or the annual timing of peak migration (1995-2015). However, we found that the earliest seasonal movements through the region occurred significantly earlier over time (1.6 days decade-1 ). Additionally, body mass and migration distance explained the magnitude of phenological changes, with the most rapid advances occurring with an assemblage of larger-bodied shorter-distance migrants. Our results provide baseline information that can be used to advance our understanding of the developing implications of climate change, urbanization, and energy development for migratory bird populations in North America.

Navigating north: how body mass and winds shape avian flight behaviours across a North American migratory flyway.

The migratory patterns of birds have been the focus of ecologists for millennia. What behavioural traits underlie these remarkably consistent movements? Addressing this question is central to advancing our understanding of migratory flight strategies and requires the integration of information across levels of biological organisation, e.g. species to communities. Here, we combine species-specific observations from the eBird citizen-science database with observations aggregated from weather surveillance radars during spring migration in central North America. Our results confirm a core prediction of migration theory at an unprecedented national scale: body mass predicts variation in flight strategies across latitudes, with larger-bodied species flying faster and compensating more for wind drift. We also find evidence that migrants travelling northward earlier in the spring increasingly compensate for wind drift at higher latitudes. This integration of information across biological scales provides new insight into patterns and determinants of broad-scale flight strategies of migratory birds.

The Health and Sociocultural Correlates of AIDS Genocidal Beliefs and Medical Mistrust Among African American MSM.

This study examined social and health-related correlates of AIDS conspiracy theories among 464 African American men who have sex with men (MSM). Exploratory factor analysis revealed two subscales within the AIDS conspiracy beliefs scale: medical mistrust and AIDS genocidal beliefs. Multiple regression analyses revealed medical mistrust and AIDS genocidal beliefs were both associated negative condom use attitudes and higher levels of internalized homonegativity. Medical mistrust was also associated with lower knowledge of HIV risk reduction strategies. Finally, we conducted bivariate regressions to examine the subsample of participants who reported being HIV-positive and currently taking HIV antiretroviral therapy (ART) to test associations between sexual behavior and HIV treatment and AIDS conspiracy theories. Among this subsample, medical mistrust was associated with having a detectable viral load and not disclosing HIV-status to all partners in the previous 3 months. Collectively, these findings have implications for HIV prevention and treatment for African American MSM.

Predictors of HIV Care Engagement, Antiretroviral Medication Adherence, and Viral Suppression Among People Living with HIV Infection in St. Petersburg, Russia.

Over 1 million HIV infections have been diagnosed in Russia, and HIV care uptake and viral suppression are very low. 241 HIV-positive individuals in St. Petersburg were enrolled through social networks, provided blood for viral load testing, and completed measures of medication-taking adherence, readiness, and self-efficacy; psychosocial well-being; and substance use. Outcomes included attending an HIV care appointment in the past 6 months, >90% ART adherence, and undetectable viral load. 26% of participants had no recent care appointment, 18% had suboptimal adherence, and 56% had detectable viral load. Alcohol use consistently predicted all adverse health outcomes. Having no recent care visit was additionally associated with being single and greater past-month drug injection frequency. Poor adherence was additionally predicted by lower medication-taking self-efficacy and lower anxiety. Detectable viral load was additionally related to younger age. Comprehensive interventions to improve HIV care in Russia must address substance abuse, anxiety, and medication-taking self-efficacy.

An Exploration of Syndemic Factors That Influence Engagement in HIV Care Among Black Men.

Syndemic theory seeks to understand the interactions and clustering of disease and social conditions and explain racial disparities in HIV. Traditionally applied to HIV risk, this study characterizes the syndemic challenges of engagement in care among Black men living with HIV and provides insight into potential HIV treatment interventions to retain vulnerable individuals in care. Interviews were conducted with 23 HIV-positive men who were either out-of-care or nonadherent to antiretroviral therapy (ART). Interviews were audio recorded, transcribed verbatim, and coded using MAXQDA qualitative software. Researchers analyzed data using thematic content analysis to identify syndemic factors associated with disengagement in care or suboptimal ART adherence among Black men. Analyses revealed the syndemic nature of four themes: intersectional stigma, depression, substance use, and poverty. Findings from this study offer numerous opportunities for intervention including social and structural-level interventions to address syndemic processes and the influence of stigma and poverty on engagement in care.

From Agricultural Benefits to Aviation Safety: Realizing the Potential of Continent-Wide Radar Networks.

Migratory animals provide a multitude of services and disservices-with benefits or costs in the order of billions of dollars annually. Monitoring, quantifying, and forecasting migrations across continents could assist diverse stakeholders in utilizing migrant services, reducing disservices, or mitigating human-wildlife conflicts. Radars are powerful tools for such monitoring as they can assess directional intensities, such as migration traffic rates, and biomass transported. Currently, however, most radar applications are local or small scale and therefore substantially limited in their ability to address large-scale phenomena. As weather radars are organized into continent-wide networks and also detect "biological targets," they could routinely monitor aerial migrations over the relevant spatial scales and over the timescales required for detecting responses to environmental perturbations. To tap these unexploited resources, a concerted effort is needed among diverse fields of expertise and among stakeholders to recognize the value of the existing infrastructure and data beyond weather forecasting.

PrEP Awareness, Familiarity, Comfort, and Prescribing Experience among US Primary Care Providers and HIV Specialists.

HIV pre-exposure prophylaxis (PrEP) was FDA approved in 2012, but uptake remains low. To characterize what would facilitate health care providers' increased PrEP prescribing, we conducted a 10-city, online survey of 525 primary care providers (PCPs) and HIV providers (HIVPs) to assess awareness, knowledge, and experience with prescribing PrEP; and, comfort with and barriers to PrEP-related activities. Fewer PCPs than HIVPs had heard of PrEP (76 vs 98%), felt familiar with prescribing PrEP (28 vs. 76%), or had prescribed it (17 vs. 64%). PCPs were less comfortable than HIVPs with PrEP-related activities such as discussing sexual activities (75 vs. 94%), testing for acute HIV (83 vs. 98%), or delivering a new HIV diagnosis (80 vs. 95%). PCPs most frequently identified limited knowledge about PrEP and concerns about insurance coverage as prescribing barriers. PCPs and HIVPs differ in needs that will facilitate their PrEP prescribing. Efforts to increase PrEP uptake will require interventions to increase the knowledge, comfort, and skills of providers to prescribe PrEP.

Correlates of Sexual HIV Risk Among African American Men Who Have Sex With Men.

OBJECTIVES: We examined correlates of condomless anal intercourse with nonmain sexual partners among African American men who have sex with men (MSM). METHODS: We recruited social networks composed of 445 Black MSM from 2012 to 2014 in Milwaukee, Wisconsin; Cleveland, Ohio; and Miami Beach, Florida. Participants reported past-3-month sexual behavior, substance use, and background, psychosocial, and HIV-related characteristics. RESULTS: Condomless anal intercourse outside main concordant partnerships, reported by 34.4% of MSM, was less likely in the case of no alcohol and marijuana use in the past 30 days, and higher risk-reduction behavioral intentions. High frequency of condomless anal intercourse acts with nonmain partners was associated with high gay community participation, weak risk-reduction intentions, safer sex not being perceived as a peer norm, low condom-use self-efficacy, and longer time since most recent HIV testing. CONCLUSIONS: Condomless anal intercourse with nonmain partners among Black MSM was primarily associated with gay community participation, alcohol and marijuana use, and risk-reduction behavioral intentions.