Improving vocational guidance through an expert system: Temporary decreasing and enhancing student self-awareness.

Background: The vocational guidance process in educational institutions faces important challenges in managing trials and errors in diagnoses. Technological tools are identified as an effective solution to address these problems. This research seeks to improve career guidance in educational institutions through the implementation of an expert system. The main objective is to reduce test processing time and achieve greater efficiency in students' self-knowledge regarding their interests, based on the personalities of the Holland Test. Methods: The development of the expert system followed a six-model approach. First, an organisational model was created to assess the scope and feasibility of the project. Next, a task and agent model was developed to investigate the impact and look for improvements. A knowledge model was then developed to analyse the relevant knowledge bases. A communication model was also developed to evaluate the communication interface of the system. Next, a design model was created to provide guidelines for the implementation of the system. Finally, the implementation of the knowledge system was carried out to ensure its correct functioning. Results: The implementation of the expert system has shown significant improvements in the vocational guidance process. It was possible to reduce the time needed to apply the test, thus optimising the psychologist's time and allowing a greater capacity for analysis. In addition, an improvement in the effectiveness of the students' self-knowledge in relation to their vocational interests based on the personalities of the Holland Test was observed. Conclusions: This study contributes to career guidance in educational institutions by introducing an innovative expert system. This technological solution optimizes the career guidance process, benefiting psychologists administering tests and students seeking self-knowledge about their career interests.

Myeloid-T cell interplay and cell state transitions associated with checkpoint inhibitor response in melanoma.

BACKGROUND: The treatment of melanoma, the deadliest form of skin cancer, has greatly benefited from immunotherapy. However, many patients do not show a durable response, which is only partially explained by known resistance mechanisms. METHODS: We performed single-cell RNA sequencing of tumor immune infiltrates and matched peripheral blood mononuclear cells of 22 checkpoint inhibitor (CPI)-naive stage III-IV metastatic melanoma patients. After sample collection, the same patients received CPI treatment, and their response was assessed. FINDINGS: CPI responders showed high levels of classical monocytes in peripheral blood, which preferentially transitioned toward CXCL9-expressing macrophages in tumors. Trajectories of tumor-infiltrating CD8+ T cells diverged at the level of effector memory/stem-like T cells, with non-responder cells progressing into a state characterized by cellular stress and apoptosis-related gene expression. Consistently, predicted non-responder-enriched myeloid-T/natural killer cell interactions were primarily immunosuppressive, while responder-enriched interactions were supportive of T cell priming and effector function. CONCLUSIONS: Our study illustrates that the tumor immune microenvironment prior to CPI treatment can be indicative of response. In perspective, modulating the myeloid and/or effector cell compartment by altering the described cell interactions and transitions could improve immunotherapy response. FUNDING: This research was funded by Roche Pharma Research and Early Development.

Real-World Data on Clinical Outcomes and Treatment Management of Advanced Melanoma Patients: Single-Center Study of a Tertiary Cancer Center in Switzerland.

BACKGROUND: Immune checkpoint inhibitors (ICIs) and BRAF/MEK inhibitors (BRAF/MEKi) have drastically changed the outcomes of advanced melanoma patients in both the resectable/adjuvant and unresectable/metastatic setting. In this follow-up analysis of real-world data, we aimed to investigate the clinical management and outcomes of advanced melanoma patients in a tertiary referral center in Switzerland approximately a decade after the introduction of ICIs and BRAF/MEKi into clinical use. Moreover, we aimed to compare the results with seminal phase 3 trials and to identify areas of high unmet clinical need. METHODS: This single-center retrospective cohort study analyzed the melanoma registry of the University Hospital Zurich, a tertiary cancer center in Switzerland, and included patients treated in the resectable/adjuvant (n = 331) or unresectable/metastatic setting (n = 375). RESULTS: In the resectable setting, adjuvant anti-PD1 or BRAF/MEKi showed a 3-year relapse-free survival (RFS) of 53% and 67.6%, respectively, and the overall median RFS was 50 months. Patients with lymph node plus in-transit metastases or with distant metastases prior to commencing adjuvant treatment had a significantly reduced overall survival (OS). In 10.9% of patients, the treatment was stopped due to toxicity, which did not affect RFS/OS, unless the duration of the treatment was <3 months. Following a relapse of the disease during the first adjuvant treatment, the median progression-free survival (PFS2) was only 6.6 months; outcomes were particularly poor for relapses that were unresectable (median PFS2 3.9 months) or occurred within the first 2 months (median PFS2 2.7 months). A second adjuvant treatment for patients with resectable relapses still showed efficacy (median RFS2 43.7 months). Elevated LDH levels in patients with an unresectable relapse was correlated with a strong reduction in OS2 (HR 9.84, p = 0.018). In the unresectable setting, first-line anti-PD1, anti-CTLA4/PD1 combination, or BRAF/MEKi showed a 5-year OS of 46.5%, 52.4%, and 49.2%, respectively. In a multivariate analysis, elevated LDH levels or the presence of brain metastases substantially shortened OS (HR > 1.78, p < 0.035). There was a non-significant trend for the improved survival of patients treated with anti-CTLA4/PD1 compared to anti-PD1 (HR 0.64, p = 0.15). After a progression on first-line therapy, the median OS2 was reduced to below two years. Elevated LDH (HR 4.65, p < 0.001) levels and widespread disease with at least three metastatic sites, particularly bone metastases (HR 2.62, p = 0.026), affected OS2. CONCLUSION: Our study offers real-world insights into the clinical management, treatment patterns, and outcomes of advanced melanoma patients in both the adjuvant and unresectable setting. Early relapses in patients undergoing adjuvant treatment pose a particular challenge but these patients are generally excluded from first-line trials. The approved first-line metastatic treatments are highly effective in the real-world setting with 5-year OS rates around 50%. However, outcomes remain poor for patients with brain metastases or who fail first-line treatment.

Size-exclusion chromatography combined with DIA-MS enables deep proteome profiling of extracellular vesicles from melanoma plasma and serum.

Extracellular vesicles (EVs) are important players in melanoma progression, but their use as clinical biomarkers has been limited by the difficulty of profiling blood-derived EV proteins with high depth of coverage, the requirement for large input amounts, and complex protocols. Here, we provide a streamlined and reproducible experimental workflow to identify plasma- and serum- derived EV proteins of healthy donors and melanoma patients using minimal amounts of sample input. SEC-DIA-MS couples size-exclusion chromatography to EV concentration and deep-proteomic profiling using data-independent acquisition. From as little as 200 µL of plasma per patient in a cohort of three healthy donors and six melanoma patients, we identified and quantified 2896 EV-associated proteins, achieving a 3.5-fold increase in depth compared to previously published melanoma studies. To compare the EV-proteome to unenriched blood, we employed an automated workflow to deplete the 14 most abundant proteins from plasma and serum and thereby approximately doubled protein group identifications versus native blood. The EV proteome diverged from corresponding unenriched plasma and serum, and unlike the latter, separated healthy donor and melanoma patient samples. Furthermore, known melanoma markers, such as MCAM, TNC, and TGFBI, were upregulated in melanoma EVs but not in depleted melanoma plasma, highlighting the specific information contained in EVs. Overall, EVs were significantly enriched in intact membrane proteins and proteins related to SNARE protein interactions and T-cell biology. Taken together, we demonstrated the increased sensitivity of an EV-based proteomic workflow that can be easily applied to larger melanoma cohorts and other indications.

"They make it too hard and too many hoops to jump": system and organizational barriers to drug treatment during epidemic rates of opioid overdose.

INTRODUCTION: The United States is currently facing an opioid overdose crisis. Research suggests that multiple interventions are needed to reduce overdose deaths including increasing access and retention to medications to treat opioid use disorders (MOUD, i.e., methadone, buprenorphine, and naltrexone) and increasing the distribution and use of naloxone, a medication that can reverse the respiratory depression that occurs during opioid overdoses. However, barriers to MOUD initiation and retention persist and discontinuations of MOUD carry a heightened risk of overdose. Many times, MOUD is not sought as a first line of treatment by people with opioid use disorder (OUD), many of whom seek treatment from medically managed withdrawal (detox) programs. Among those who do initiate MOUD, retention is generally low. The present study examines the treatment experiences of people who use opioids in three states, Connecticut, Kentucky, and Wisconsin. METHODS: We conducted in-depth interviews with people who use opioids in a rural, urban, and suburban area of three states: Connecticut, Kentucky and Wisconsin. Data analysis was collaborative and key themes were identified through multiple readings, coding of transcripts and discussion with all research team members. RESULTS: Results reveal a number of systemic issues that reduce the likelihood that people initiate and are retained on MOUD including the ubiquity of detox as a first step in drug treatment, abstinence requirements and requiring patients to attend group treatment. MOUD-related stigma was a significant factor in the kinds of treatment participants chose and their experiences in treatment. CONCLUSIONS: Interventions to reduce MOUD stigma are needed to encourage MOUD as a first course of treatment. Eliminating abstinence-based rules for MOUD treatment may improve treatment retention and decrease overdose risk.

INPP5A phosphatase is a synthetic lethal target in GNAQ and GNA11-mutant melanomas.

Activating mutations in GNAQ/GNA11 occur in over 90% of uveal melanomas (UMs), the most lethal melanoma subtype; however, targeting these oncogenes has proven challenging and inhibiting their downstream effectors show limited clinical efficacy. Here, we performed genome-scale CRISPR screens along with computational analyses of cancer dependency and gene expression datasets to identify the inositol-metabolizing phosphatase INPP5A as a selective dependency in GNAQ/11-mutant UM cells in vitro and in vivo. Mutant cells intrinsically produce high levels of the second messenger inositol 1,4,5 trisphosphate (IP3) that accumulate upon suppression of INPP5A, resulting in hyperactivation of IP3-receptor signaling, increased cytosolic calcium and p53-dependent apoptosis. Finally, we show that GNAQ/11-mutant UM cells and patients' tumors exhibit elevated levels of IP4, a biomarker of enhanced IP3 production; these high levels are abolished by GNAQ/11 inhibition and correlate with sensitivity to INPP5A depletion. Our findings uncover INPP5A as a synthetic lethal vulnerability and a potential therapeutic target for GNAQ/11-mutant-driven cancers.

The Relative Influence of Perceived Immigration Laws and Consequences on HIV Testing Among US Latino Immigrants.

The CDC recommends that persons aged 13-64 receive an HIV test at least once in their lifetime and that some groups test annually or more frequently. Nearly one-half of US Latino immigrants have never been tested for HIV. To the extent that immigration-related laws deter documented and undocumented immigrants from engaging in communicable disease control measures, these laws undermine public health efforts. 1750 noncitizen adult, sexually active, Spanish-speaking Latino immigrants across four cities in the US completed a cross-sectional survey assessing perceptions of immigration-related laws and immigration consequences related to HIV testing and diagnosis. Participants were recruited in-person by staff in community settings, through flyers posted in places frequented by Latino immigrants, and by word-of-mouth through snowball sampling. Outcomes were whether participants had ever received an HIV test and whether they tested in the previous 12 months. Multivariable analyses examined the relative contribution of perceived immigration laws and consequences on HIV testing behaviors when considering established predictors of HIV testing. Perceptions of HIV-related immigration laws and immigration consequences was a significant predictor of never having had an HIV test even when considered relative to common predictors of HIV testing. The influence of perceived immigration laws and consequences on testing in the previous 12 months was not significant in multivariable analysis. Perceived HIV-related immigration laws and consequences appear to be a substantial contributor to reluctance to be tested for HIV among Latino immigrants who have never been tested. Effective interventions should be developed to address these.

RESUMEN: El CDC recomienda que las personas de 13 a 64 años se hagan una prueba del VIH al menos una vez en la vida y que algunos grupos se hagan la prueba anualmente o con mayor frecuencia. Casi la mitad de los inmigrantes latinos de los Estados Unidos nunca se han hecho la prueba del VIH. En la medida en que las leyes relacionadas con la inmigración disuadan a los inmigrantes documentados e indocumentados de participar en medidas de control de enfermedades transmisibles, estas leyes socavan los esfuerzos de salud pública. 1750 inmigrantes latinos adultos no ciudadanos, sexualmente activos y de habla hispana en cuatro ciudades de EE. UU. completaron una encuesta transversal que evaluó las percepciones de las leyes relacionadas con la inmigración y de las consecuencias de la inmigración relacionadas con las pruebas y el diagnóstico del VIH. Los participantes fueron reclutados en persona en contextos comunitarios, a través de volantes publicados en lugares frecuentados por inmigrantes latinos y de boca en boca a través de muestras de bola de nieve. Las variables dependientes fueron si los participantes se habían hecho una prueba del VIH alguna vez y si se habían hecho la prueba en los últimos 12 meses. Los análisis multivariados examinaron la contribución relativa de la percepción de las leyes de inmigración y de las consecuencias de inmigración sobre los comportamientos relativo a las pruebas del VIH, controlando por predictores conocidos de las pruebas del VIH. Las percepciones de las leyes de inmigración relacionadas con el VIH y las consecuencias de la inmigración fueron un predictor significativo de nunca haberse realizado una prueba del VIH, aun considerando los predictores comunes de la prueba del VIH. La influencia de la percepción de las leyes de inmigración y de las consecuencias de la inmigración sobre la prueba en los últimos 12 meses no fue significativa en el análisis multivariado. Las leyes de inmigración y las consecuencias percibidas relacionadas con el VIH parecen contribuir sustancialmente a la renuencia a hacerse la prueba del VIH entre los inmigrantes latinos que nunca se han hecho la prueba. Deben desarrollarse intervenciones efectivas para abordar esta renuencia.

Proteomic Profiling of Advanced Melanoma Patients to Predict Therapeutic Response to Anti-PD-1 Therapy.

PURPOSE: Despite high clinical need, there are no biomarkers that accurately predict the response of patients with metastatic melanoma to anti-PD-1 therapy. EXPERIMENTAL DESIGN: In this multicenter study, we applied protein depletion and enrichment methods prior to various proteomic techniques to analyze a serum discovery cohort (n = 56) and three independent serum validation cohorts (n = 80, n = 12, n = 17). Further validation analyses by literature and survival analysis followed. RESULTS: We identified several significantly regulated proteins as well as biological processes such as neutrophil degranulation, cell-substrate adhesion, and extracellular matrix organization. Analysis of the three independent serum validation cohorts confirmed the significant differences between responders (R) and nonresponders (NR) observed in the initial discovery cohort. In addition, literature-based validation highlighted 30 markers overlapping with previously published signatures. Survival analysis using the TCGA database showed that overexpression of 17 of the markers we identified correlated with lower overall survival in patients with melanoma. CONCLUSIONS: Ultimately, this multilayered serum analysis led to a potential marker signature with 10 key markers significantly altered in at least two independent serum cohorts: CRP, LYVE1, SAA2, C1RL, CFHR3, LBP, LDHB, S100A8, S100A9, and SAA1, which will serve as the basis for further investigation. In addition to patient serum, we analyzed primary melanoma tumor cells from NR and found a potential marker signature with four key markers: LAMC1, PXDN, SERPINE1, and VCAN.

Total recovery of visual acuity in a pediatric patient with compressive optic neuropathy secondary to sphenoid sinus mucocele / Recuperação total da acuidade visual na neuropatia óptica compressiva secundária à mucocele do seio esfenoidal em paciente pediátrico

ABSTRACT We present an unusual case of a 13-year-old male pediatric patient with a diagnosis of sphenoid sinus mucocele. The patient suffered a progressive loss of visual acuity over three months followed by a total recovery of his visual acuity after surgery. The patient presented at the emergency room complaining of progressive loss of visual acuity in his left eye which decreased to hand motion over the preceding months. Imaging studies revealed a cystic mass, suggestive of sphenoid sinus mucocele, which was causing compressive optic neuropathy and proptosis. The patient was scheduled for a sphenoidectomy and resection of the mass. Three days after surgery, the patient's visual acuity in the left eye was 20/20, indicating complete recovery from his symptoms. We suggest that the excellent outcome in this patient may be attributable to his age. His ongoing physical development might have been the decisive factor in the recovery of his visual acuity following compressive optic neuropathy secondary to sphenoid sinus mucocele. Further research is needed to verify this proposed explanation.

RESUMO Apresentamos um caso incomum de paciente pediátrico com diagnóstico de mucocele de seio esfenoidal, que apresentou perda progressiva da acuidade visual ao longo de três meses, resultando em recuperação total da acuidade visual após a cirurgia. Paciente do sexo masculino, 13 anos, procurou o pronto-socorro, queixando-se de perda progressiva da acuidade visual do olho esquerdo nos últimos três meses. Exames de imagem revelaram uma massa cística sugestiva de mucocele de seio esfenoidal, causando neuropatia óptica compressiva e proptose. O paciente foi agendado para esfenoidectomia e ressecção da massa. Três dias após a cirurgia, a acuidade visual do paciente no olho esquerdo era de 20/20, apresentando recuperação completa dos sintomas. Diante dos resultados de nosso paciente, sugerimos que a idade do paciente pode ser decisiva na recuperação da acuidade visual de uma neuropatia óptica compressiva secundária à mucocele de seio esfenoidal. Mais pesquisas são necessárias para verificação desses dados.

Fight COVID Milwaukee protective behaviors and risk communications associated with the COVID-19 pandemic.

The COVID-19 pandemic has had a major impact on society, causing significant disruptions to everyday life. Risk communication strategies can play an important role in risk management as they allow individuals to prepare for and respond to public health emergencies appropriately. The aim of this study is to investigate public risk behaviors, perceptions of risk and risk communication, and experiences with COVID-19 to better understand the impact of COVID-19 on our community and to better inform public health decisions about communicating and reducing personal risk. Nine virtual focus groups were conducted with 79 residents of Milwaukee County. Audio transcripts of focus group recordings were qualitatively analyzed using MAXQDA. Predominant themes identified include public risk protective behaviors, the emotional toll associated with lockdown measures, and risk communication. Our findings provide a better understanding of how adults, African American and Hispanic groups in particular, viewed the risk communications and protective behaviors associated with COVID-19, how their lives were impacted by the pandemic, and how to effectively communicate public information about personal risk. These findings can help guide risk communication efforts and public health policy interventions for potential infection outbreaks in the future.

Latino migrants' healthcare use in the US and perceived immigration laws and consequences: A multivariable analysis.

BACKGROUND: Using healthcare, whether for routine preventative examinations, chronic condition management, or emergent conditions, is an essential element of achieving and maintaining health. Over 44 million migrants live in the US today and nearly half (44.6 %) are Latino. To the extent that immigration law-related concerns deter US Latino migrants from using healthcare, they jeopardize the health of a substantial though marginalized US subpopulation. METHODS: A multistate sample (N = 1750) of noncitizen adult, Spanish speaking Latino migrants (both undocumented and documented) living in the US completed a cross-sectional survey comprising a scale assessing perceptions of immigration laws and consequences related to healthcare use and whether they had received and/or needed but did not receive healthcare in the previous 12-months. Participants were recruited in community settings and by word-of-mouth. Univariate analyses examined associations among study outcomes and common predictors of healthcare use. Multivariable analyses examined the relative contribution of perceived immigration laws and consequences on healthcare use and unmet need. RESULTS: Perceptions of immigration laws and immigration consequences were a significant predictor of not having received healthcare in the previous 12-months and having needed and not received healthcare in the same period, even when considered relative to common predictors of healthcare use. Immigration documentation status and preferred language predicted healthcare use in univariate analyses but not in the multivariable model. CONCLUSIONS: Perceived immigration laws and consequences related to healthcare use may influence migrants' healthcare use. Effective interventions should be developed to address immigration-related concerns.

Spatial accessibility to health facilities among pregnant women with and without exposure to intimate partner violence in Uganda.

BACKGROUND: Poor physical access to health facilities could increase the likelihood of undetected intimate partner violence (IPV) during pregnancy. We aimed to determine sub-regional differences and associations between spatial accessibility to health facilities and IPV among pregnant women in Uganda. METHOD: Weighted cross-sectional analyses were conducted using merged 2016 Uganda Demographic and Health Survey and 2014 Uganda Bureau of Statistics health facility datasets. Our study population were 986 women who self-reported being currently pregnant and responded to IPV items. Outcome was spatial accessibility computed as the near point linear distance [< 5 km (optimal) vs. ≥ 5 km (low)] between women's enumeration area and health facility according to government reference cutoffs. Primary independent variable (any IPV) was defined as exposure to at least one of physical, emotional, and sexual IPV forms. Logistic regression models were sequentially adjusted for covariates in blocks based on Andersen's behavioral model of healthcare utilization. Covariates included predisposing (maternal age, parity, residence, partner controlling behavior), enabling (wealth index, occupation, education, economic empowerment, ANC visit frequency), and need (wanted current pregnancy, difficulty getting treatment money, afraid of partner, and accepted partner abuse) factors. RESULTS: Respondents' mean age was 26.1 years with ± 9.4 standard deviations (SD), mean number of ANC visits was 3.8 (± 1.5 SD) and 492/986 (49.9%) pregnant women experienced IPV. Median spatial accessibility to the nearest health facility was 4.1 km with interquartile range (IQR) from 0.2 to 329.1 km. Southwestern, and Teso subregions had the highest average percentage of pregnant women experiencing IPV (63.8-66.6%) while Karamoja subregion had the highest median spatial accessibility (7.0 to 9.3 km). In the adjusted analysis, pregnant women exposed to IPV had significantly higher odds of low spatial accessibility to nearest health facilities when compared to pregnant women without IPV exposure after controlling for enabling factors in Model 2 (aOR 1.6; 95%CI 1.2, 2.3) and need factors in Model 3 (aOR 1.5; 95%CI 1.1, 3.8). CONCLUSIONS: Spatial accessibility to health facilities were significantly lower among pregnant women with IPV exposure when compared to those no IPV exposure. Improving proximity to the nearest health facilities with ANC presents an opportunity to intervene among pregnant women experiencing IPV. Focused response and prevention interventions for violence against pregnant women should target enabling and need factors.

Healthcare provider experiences interacting with survivors of intimate partner violence: a qualitative study to inform survivor-centered approaches.

BACKGROUND: Intimate partner violence (IPV) remains a pervasive form of gender-based violence (GBV) that is largely undisclosed, especially among women seeking healthcare services in Uganda. Prioritizing survivor needs may improve IPV disclosure. This study explores healthcare worker experiences from provider-patient interactions with survivors seeking antenatal care services (ANC) in Uganda. METHODS: In-depth interviews were conducted among twenty-eight experienced healthcare providers in a rural and an urban-based ANC clinic in Eastern and Central Uganda. Providers were asked what they viewed as the needs and fears of women identified as having experienced any form of IPV. Iterative, inductive/deductive thematic analysis was conducted to discover themes regarding perceived needs, fears, and normalizing violence experienced by IPV survivors. RESULTS: According to healthcare providers, IPV survivors are unaware of available support services, and have need for support services. Providers reported that some survivors were afraid of the consequences of IPV disclosure namely, community stigma, worries about personal and their children's safety, retaliatory abuse, fear of losing their marriage, and partners' financial support. Women survivors also blamed themselves for IPV. Contextual factors underlying survivor concerns included the socio-economic environment that 'normalizes' violence, namely, some cultural norms condoning violence, and survivors' unawareness of their human rights due to self-blame and shame for abuse. CONCLUSIONS: We underscore a need to empower IPV survivors by prioritizing their needs. Results highlight opportunities to create a responsive healthcare environment that fosters IPV disclosure while addressing survivors' immediate medical and psychosocial needs, and safety concerns. Our findings will inform GBV prevention and response strategies that integrate survivor-centered approaches in Uganda.

Intimate partner violence and antenatal care utilization predictors in Uganda: an analysis applying Andersen's behavioral model of healthcare utilization.

BACKGROUND: Optimal utilization of antenatal care (ANC) services improves positive pregnancy experiences and birth outcomes. However, paucity of evidence exists on which factors should be targeted to increase ANC utilization among women experiencing intimate partner violence (IPV) in Uganda. OBJECTIVE: To determine the independent association between IPV exposure and ANC utilization as well as the predictors of ANC utilization informed by Andersen's Behavioral Model of Healthcare Utilization. METHODS: We analyzed 2016 Uganda Demographic and Health Survey data that included a sample of 1,768 women with children aged 12 to 18 months and responded to both ANC utilization and IPV items. Our outcome was ANC utilization, a count variable assessed as the number of ANC visits in the last 12 months preceding the survey. The key independent variable was exposure to any IPV form defined as self-report of having experienced physical, sexual and/or emotional IPV. Covariates were grouped into predisposing (age, formal education, religion, problem paying treatment costs), enabling (women's autonomy, mass media exposure), need (unintended pregnancy, parity, history of pregnancy termination), and healthcare system/environmental factors (rural/urban residence, spatial accessibility to health facility). Poisson regression models tested the independent association between IPV and ANC utilization, and the predictors of ANC utilization after controlling for potential confounders. RESULTS: Mean number of ANC visits (ANC utilization) was 3.71 visits with standard deviation (SD) of ± 1.5 respectively. Overall, 60.8% of our sample reported experiencing any form of IPV. Any IPV exposure was associated with lower number of ANC visits (3.64, SD ± 1.41) when compared to women without IPV exposure (3.82, SD ± 1.64) at p = 0.013. In the adjusted models, any IPV exposure was negatively associated with ANC utilization when compared to women with no IPV exposure after controlling for enabling factors (Coef. -0.03; 95%CI -0.06,-0.01), and healthcare system/environmental factors (Coef. -0.06; 95%CI -0.11,-0.04). Predictors of ANC utilization were higher education (Coef. 0.27; 95%CI 0.15,0.39) compared with no education, high autonomy (Coef. 0.12; 95%CI 0.02,0.23) compared to low autonomy, and partial media exposure (Coef. 0.06; 95%CI 0.01,0.12) compared to low media exposure. CONCLUSION: Addressing enabling and healthcare system/environmental factors may increase ANC utilization among Ugandan women experiencing IPV. Prevention and response interventions for IPV should include strategies to increase girls' higher education completion rates, improve women's financial autonomy, and mass media exposure to improve ANC utilization in similar populations in Uganda.

Community focus groups about a COVID-19 individual risk assessment tool: access, understanding and usefulness.

To make informed COVID-19 related decisions, individuals need information about their personal risks and how those risks may vary with specific demographic and health characteristics. The Fight COVID Milwaukee web-based risk assessment tool allows for assessment of COVID-19 mortality risk as a function of personal and neighborhood characteristics. The purpose of this study is to explore public understanding of this risk assessment tool and risk perception through community focus groups. Individuals were recruited from the general adult population in Milwaukee County, Wisconsin, USA, to participate in nine online focus groups where the risk assessment tool was presented for feedback. Three main themes were identified in the focus groups regarding the web-based risk assessment tool: some challenges in accessibility, variable ease of understanding, and personal usefulness but uncertain value for others. This paper explores how members of the community interpret individual risk assessments and life expectancy estimations, and how these vary with age, gender, race/ethnicity, socioeconomic status, and pre-existing comorbidities.

Dynamic thresholding and tissue dissociation optimization for CITE-seq identifies differential surface protein abundance in metastatic melanoma.

Multi-omics profiling by CITE-seq bridges the RNA-protein gap in single-cell analysis but has been largely applied to liquid biopsies. Applying CITE-seq to clinically relevant solid biopsies to characterize healthy tissue and the tumor microenvironment is an essential next step in single-cell translational studies. In this study, gating of cell populations based on their transcriptome signatures for use in cell type-specific ridge plots allowed identification of positive antibody signals and setting of manual thresholds. Next, we compare five skin dissociation protocols by taking into account dissociation efficiency, captured cell type heterogeneity and recovered surface proteome. To assess the effect of enzymatic digestion on transcriptome and epitope expression in immune cell populations, we analyze peripheral blood mononuclear cells (PBMCs) with and without dissociation. To further assess the RNA-protein gap, RNA-protein we perform codetection and correlation analyses on thresholded protein values. Finally, in a proof-of-concept study, using protein abundance analysis on selected surface markers in a cohort of healthy skin, primary, and metastatic melanoma we identify CD56 surface marker expression on metastatic melanoma cells, which was further confirmed by multiplex immunohistochemistry. This work provides practical guidelines for processing and analysis of clinically relevant solid tissue biopsies for biomarker discovery.

Institutional violence from police militarization and drug cartel wars as a 'Big Event' and its influence on drug use harms and HIV risk in people who inject drugs on the U.S.-Mexico border.

BACKGROUND: Globally, the US-Mexico Border is one of the largest drug trafficking regions, with Ciudad Juarez (CJ) and El Paso (EP) making up the second-largest border crossing in the world. Border communities are places where the risk of drug use harm and infectious diseases such as HIV are augmented due to the confluence of factors operating across the physical, social, economic and policy environment. Although the two cities are economically, culturally, and socially intertwined, each has distinct criminal justice systems and policy practices aimed at curtailing substance use. Between 2008 and 2011, the CJ/EP region experienced an unprecedented level of violence that stemmed from the intersection of police militarization and drug cartel wars, which profoundly shaped every aspect of life. Little research has documented the impact of drug cartel wars on the drug use and health harms of people who inject drugs (PWID) living in CJ and EP. The purpose of the study is to understand the effect that the drug cartel war had on the drug use harms and HIV risk of PWID. METHODS: We conducted 40 in-depth interviews with people who inject drugs who resided in CJ or EP and had used heroin or crack cocaine in the last 30 days, and asked how police militarization and drug cartel war affected their daily lives. The risk environment framework informed the analysis and interpretation of findings. RESULTS: Findings indicated that the risk environment was profoundly altered as PWID residing in CJ experienced profound changes in their daily lives that promoted engagement in behaviors that increased drug use and health harms including HIV risk, exacerbated trauma, and prevented use of substance use treatment and harm reduction services. The risk environment was also altered in EP, where PWID experienced drug supply shortages, violent policing practices, and reduced availability of harm reduction services. Findings underscore the permeability of risk environments across geographical borders. CONCLUSION: The intersection of law enforcement militarization and drug cartel wars can be conceptualized as a 'big event' because it disrupts the drug market economy, leads to drug shortages, promotes entrance into the drug market economy by people who use drugs, reshapes drug use sites, and constrains the provision of harm reduction services. The stability of the harm reduction system in CJ was negatively impacted and limited the ability of individuals to reduce harm. Our findings show that drug cartel wars render the CJ/EP region extremely susceptible to drug use and health harms, while also creating vulnerability by severely restricting its ability to respond. Traditional recommendations to intervene to limit the impact of risk environments on the drug use harms of PWID need to be reconsidered in the context of drug cartel wars.

Water, Sanitation, and Hygiene Challenges in Informal Settlements in Kampala, Uganda: A Qualitative Study.

Diarrhea causes 1.6 million deaths annually, including 525,000 children. Further, chronic diarrhea puts children at risk for mineral deficiencies, malnutrition, and stunting which, in turn, can result in cognitive deficits, poor performance in school, and decreased disease immunity in adulthood. Most diarrhea is caused by water contaminated by fecal matter. Interventions to improve clean water and sanitation can save lives; however, challenges persist in informal settlements. In this study, we explored the views of residents of informal settlements regarding water and sanitation in their communities. Focus group interviews were conducted with residents of 6 informal settlements in Kampala, Uganda (n = 165 people), and 6 key informant interviews were conducted with governmental and nongovernmental organizations that work to improve informal settlements or provide services to them. The results from this study demonstrate that, although these informal settlements had many infrastructure "upgrades" such as latrines and toilets, water taps, wells, and garbage collection and drainage systems, the water, sanitation, and hygiene (WASH) system and its components largely failed due to point-of-use charges of water taps and toilets and the difficulty of emptying cesspits. Our results suggest that WASH must be considered a system and that multiple upgrading efforts are needed for WASH systems to work, including road construction and better oversight of fecal sludge disposal.

Shoulder problems after percutaneous antegrade intramedullary nailing in humeral diaphyseal fractures using contemporary straight third-generation nail.

BACKGROUND: Antegrade intramedullary nailing in humeral shaft fracture has been abandoned by certain orthopedic surgeons because of rotator cuff injury caused by first- and second-generation intramedullary nails (IMNs). However, only a few studies have specifically addressed the results of antegrade nailing for the treatment of humeral shaft fractures with a straight third-generation IMN; thus, complications need to be re-evaluated. We hypothesized that fixation of displaced humeral shaft fractures with a straight third-generation antegrade IMN with the percutaneous technique avoid shoulder problems (stiffness and pain) incurred by first- and second-generation IMNs. METHODS: This was a retrospective, single-center, nonrandomized study of 110 patients with a displaced humeral shaft fracture between 2012 and 2019 treated surgically with a long third-generation straight IMN. Mean follow-up was 35.6 months (range, 15-44 months). RESULTS: There were 73 women and 37 men with a mean age of 64.7 ± 19 years. All fractures were closed (37.3% 12A1, 13.6% 12B2, and 13.6% 12B3 AO/OTA classification). Mean Constant score was 82 ± 19, Mayo Elbow Performance Score 96 ± 11 and the mean EQ-5D visual analog scale score was 69.7 ± 21.5. Mean forward elevation 150° ± 40°, abduction 148° ± 45°, and external rotation 38° ± 15°. Symptoms associated with rotator cuff disease were present in 6.4%. Evidence of radiographic fracture healing was detected in all but 1 case. One postoperative nerve injury and 1 adhesive capsulitis were present. Overall, 6.3% underwent second surgeries (4.5% were minor surgeries like hardware removal). CONCLUSION: Percutaneous antegrade intramedullary nailing of humeral shaft fractures with a straight third-generation nail considerably reduced complications related to shoulder problems and achieved good functional results.

Efficacy and Safety of Two-Drug Regimens with Dolutegravir plus Rilpivirine or Lamivudine in HIV-1 Virologically Suppressed People Living with HIV.

BACKGROUND: The high effectiveness and safety of the two-drug (2DRs) strategy using dolutegravir (DTG) plus lamivudine (3TC) have led to international guidelines recommending their use for treatment-naive HIV patients. In virologically suppressed patients, de-escalating from 3DRs to DTG plus either rilpivirine (RPV) or 3TC has shown high rates of virological suppression. OBJECTIVES: This study aimed to compare the real-life data of two multicenter Spanish cohorts of PLWHIV treated with DTG plus 3TC (SPADE-3) or RPV (DORIPEX) as a switch strategy, not only in terms of virological suppression, safety, and durability but also in terms of immune restoration. The primary endpoint was the percentage of patients with virological suppression on DTG plus 3TC and DTG plus RPV at weeks 24 and 48. The secondary outcomes included the proportion of patients who experienced the protocol-defined loss of virological control by week 48; changes in immune status in terms of CD4+ and CD8+ T lymphocyte counts and the CD4+/CD8+ ratio; the rate, incidence, and reasons for discontinuation of treatment over the 48-week study period; and safety profiles at weeks 24 and 48. METHODS: We conducted a retrospective, observational, multicenter study of 638 and 943 virologically suppressed HIV-1-infected patients in two cohorts who switched to 2DRs with DTG plus RPV or DTG plus 3TC. RESULTS: The most frequent reasons for starting DTG-based 2DRs were treatment simplification/pill burden or drug decrease. The virological suppression rates were 96.9%, 97.4%, and 99.1% at weeks 24, 48, and 96, respectively. The proportion of patients with virological failure over the 48-week study period was 0.01%. Adverse drug reactions were uncommon. Patients treated with DTG+3TC increased CD4, CD8, and CD4/CD8 parameters at 24 and 48 weeks. CONCLUSIONS: We conclude that DTG-based 2DRs (combined with 3TC or RPV) in clinical practice were effective and safe as a switching strategy, with a low VF and high viral suppression rates. Both regimens were well tolerated, and ADR rates were low, including neurotoxicity and induced treatment discontinuations.