Open-Label, Multicenter, Phase I/II, First-in-Human Trial of TK216: A First-Generation EWS::FLI1 Fusion Protein Antagonist in Ewing Sarcoma.

PURPOSE: Ewing Sarcoma (ES), a rare cancer with a pathognomonic translocation resulting in the Ewing sarcoma gene (EWS)::FLI1 oncoprotein, has a poor prognosis in the relapsed/refractory (R/R) setting. Tokalas (TK)216 was designed to bind EWS::FLI1 proteins directly, disrupt protein-protein interactions, and inhibit transcription factor function. TK216 plus vincristine showed synergistic activity in preclinical tumor models. To our knowledge, we report the results of a first-in-class, first-in-human phase I/II trial of TK216 in R/R ES. PATIENTS AND METHODS: TK216 was administered intravenously as a continuous infusion to patients with R/R ES in 11 cohorts. The dosing duration of 7 days was later extended to 10, 14, and 28 days. Vincristine could be added on day 1 after cycle 2, per investigators' choice. The trial used a 3 + 3 design with an expansion cohort at the recommended phase II dose (RP2D). RESULTS: A total of 85 patients with a median age of 27 years (range, 11-77) were enrolled. The maximum tolerated dose for the 14-day infusion of TK216, 200 mg/m2 once daily, was determined in cohort 9 and selected as the RP2D. The median previous number of systemic therapies regimens was three (range, 1-10). The most frequent-related adverse events in patients treated at the RP2D included neutropenia (44.7%), anemia (29.4%), leukopenia (29.4%), febrile neutropenia (15.3%), thrombocytopenia (11.8%), and infections (17.6%). In cohorts 9 and 10, two patients had a complete response, one had a partial response, and 14 had stable disease; the 6-month progression-free survival was 11.9%. There were no responses among the eight patients in cohort 11. CONCLUSION: TK216 administered as 14-day continuous infusion with or without vincristine was well tolerated and showed limited activity at the RP2D in R/R ES.

Exit Strategy: Balancing the Risks and Rewards of Antiseizure Medication Withdrawal.

The majority of people with epilepsy achieves long-term seizure-freedom and may consider withdrawal of their anti-seizure medications (ASMs). Withdrawal of ASMs can yield substantial benefits but may be associated with potential risks. This review critically examines the existing literature on ASM withdrawal, emphasizing evidence-based recommendations, where available. Our focus encompasses deprescribing strategies for individuals who have attained seizure freedom through medical treatment, those who have undergone successful epilepsy surgery, and individuals initiated on ASMs following acute symptomatic seizures. We explore state-of-the-art prognostic models in these scenarios that could guide the decision-making process. The review underscores the importance of a collaborative shared-decision approach between patients, caregivers, and physicians. We describe the subjective and objective factors influencing these decisions and illustrate how trade-offs may be effectively managed in practice.

Self-initiated lifestyle changes during a fasting-mimicking diet programme in patients with type 2 diabetes: a mixed-methods study.

BACKGROUND: Lifestyle changes, especially regarding diet quality and physical activity, are important in the management of type 2 diabetes (T2D). This mixed-methods study explores self-initiated lifestyle changes in patients with T2D who followed a periodic fasting-mimicking diet (FMD). METHODS: Quantitative data were obtained from the Fasting In diabetes Treatment trial (November 2018 to August 2021) in which 100 participants with T2D, using metformin only or no medication, were randomised to receive a monthly 5-day FMD for twelve months next to usual care, or usual care only. Diet quality and physical activity questionnaires were completed at baseline, six and twelve months. Changes over time were analysed using linear mixed models. Focus groups were organized with FMD participants to explore experiences regarding self-initiated lifestyle changes. The qualitative data was analysed using the Theoretical Domains Framework. RESULTS: Questionnaires were available from 49 FMD participants and 43 controls. No differences in diet quality were found. Total physical activity in the FMD participants changed from 34.6 to 38.5 h per week (h/wk) from baseline to twelve months, while in controls it changed from 34.9 to 29.0 h/wk (between group difference, p = 0.03). In six focus groups with FMD participants (n = 20), individual participants perceived the FMD as an encouragement for (minor) lifestyle changes. There were no barriers to behaviour change related to the FMD. Important facilitators of healthy behaviour were an increase in awareness of the impact of lifestyle on health (knowledge), better physical fitness (physical) and health improvement (reinforcement). Facilitators unrelated to the FMD included family support (social influences) and opportunities in the neighbourhood (environmental context and resources), while barriers unrelated to the FMD were experiencing health problems (physical) and social events (social influences). CONCLUSIONS: Using an FMD for five consecutive days per month did not affect diet quality in between FMD periods in quantitative analysis, but increased the number of hours per week spent on physical activity. Qualitative analysis revealed self-initiated improvements in both diet quality and physical activity in individual participants using an FMD. Healthcare professionals could use an FMD programme as a 'teachable moment' to stimulate additional lifestyle changes. TRIAL REGISTRATION: ClinicalTrials.gov; NCT03811587. Registered 22 January 2019.

The Effects of the COVID-19 Pandemic on the Pattern of Fractures in Taif City, Saudi Arabia.

BACKGROUND:  The COVID-19 pandemic forced the world to take restricted orders to control the spread of SARS-CoV-2 by limiting and controlling people's movement inside their countries. According to previous studies, the shutdown and quarantine affected orthopedic trauma presentations and patterns in many countries. This study aimed to show the change in the pattern of fractures in Taif City, Saudi Arabia, during the curfew period during the COVID-19 pandemic in 2020 and compare it with the same period in 2019. METHODS:  A retrospective study of all patients with fractures who came to the emergency room and were treated by the orthopedic department at Alhada Armed Forces Hospital, King Abdulaziz Specialist Hospital, and King Faisal Medical Complex, Taif City. During partial and total lockdowns between March 23 and June 21, 2020, Data was collected from this period during September 2023. Demographics, fracture type and site, mechanism of injury, length of admission, if admitted, and the management plan were documented. These fracture cases were compared with those within the same period of March-June from the previous year. All statistical analysis was done using two-tailed tests. RESULTS:  There was a decrease in the number of fractures at the time of quarantine, with 69 cases in the three months of curfew in 2020, compared to 184 cases in the same three months in 2019. There was a significant difference in the anatomical site of fractures between the two years, with decreased radius/ulna fractures (P= 0.035) and foot fractures (P=0.010). Most fractures during the lockdown were due to home accidents, with a significant decrease in motor vehicle accidents (P=0.009). CONCLUSION:  The pattern of fractures in Taif City was affected by the movement restriction during the COVID-19 pandemic. The number of fractures decreased by 62.5% during the quarantine compared with the pre-pandemic period. A significant decrease was noted in the number of hospitalized patients (33%) during the COVID-19 lockdown compared to 65.8% in the pre-pandemic period.

Persistent Smell Disorders After COVID-19 Infection and Their Impact on Quality of Life.

Background The COVID-19 pandemic has led to various health challenges, including the disruption of people's sense of smell. Olfactory disorders have been reported as a lingering consequence of COVID-19, with diverse patterns of smell dysfunction experienced by patients. Objectives This study aimed to investigate the impact of persistent smell disorders on the quality of life of individuals who recovered from COVID-19 in Taif, Saudi Arabia. Methodology A descriptive cross-sectional study was conducted in Taif, Saudi Arabia, between October 2023 and January 2024. The study included adults with a history of PCR-confirmed COVID-19 infection in Taif city. Data were collected using a validated online survey employing a convenience sampling technique. Statistical analysis was carried out using IBM SPSS Statistics for Windows, Version 26.0 (Released 2019; IBM Corp., Armonk, New York, United States), and chi-squared tests were used to assess the relationships. Results The study included 429 participants. A total of 52.7% of the respondents reported a loss of smell after recovering from COVID-19, and 14.9% reported a persistent loss of their sense of smell. The most common types of smell disorders experienced were hyposmia, anosmia, and parosmia. The study revealed emotional distress, changes in eating habits, and social impact among participants with smell disorders. Conclusion This study highlights the high prevalence of persistent smell disorders among individuals who recovered from COVID-19 in Taif, Saudi Arabia. The findings emphasize the complex nature of these disorders and their impact on patients' quality of life. This study contributes valuable information that can inform healthcare practices and support services for individuals experiencing post-COVID-19 smell disorders.

HPTN 083-02: factors influencing adherence to injectable PrEP and retention in an injectable PrEP study.

INTRODUCTION: HPTN 083 demonstrated the superiority of long-acting cabotegravir (CAB-LA) versus daily oral emtricitabine/tenofovir disoproxil fumarate (TDF/FTC) as pre-exposure prophylaxis (PrEP) among cisgender men and transgender women who have sex with men (MSM/TGW). HPTN 083 provided the first opportunity to understand experiences with injectable PrEP in a clinical trial. METHODS: Participants from two US sites (Chicago, IL and Atlanta, GA) and one international site (Rio de Janeiro, Brazil) were purposively sampled for individual qualitative interviews (N = 40), between November 2019 and March 2020, to explore trial experiences, barriers to adherence and other factors that may have impacted study implementation or outcomes. The blinded phase ended early due to efficacy; this analysis includes interviews conducted prior to unblinding with three groups defined by adherence (i.e. injection visit attendance): adherent (n = 27), non-adherent (n = 12) and early discontinuers (n = 1). Data were organized using NVivo software and analysed using content analysis. RESULTS: Participants (mean age: 27) were primarily cisgender MSM (90%) and Black/African American (60%). Reasons for trial enrolment and PrEP use included a preference for using HIV prevention medication versus treatment in the event of HIV acquisition; the ability to enhance health via study-related education and services; access to a novel, convenient HIV prevention product at no cost; and contributing to MSM/TGW communities through research. Participants contrasted positive experiences with study staff with their routine clinical care, and emphasized increased scheduling flexibility, thorough communication, non-judgemental counselling and open, affirming environments (e.g. compassion, less stigma) as adherence facilitators. Injection experiences were positive overall; some described early injection-related anxiety, which abated with time and when given some measure of control (e.g. pre-injection countdown), and minimal injection site discomfort. Some concerns and misperceptions about injectable PrEP were reported. Barriers to adherence, across all adherence categories, included structural factors (e.g. financial constraints, travel) and competing demands (e.g. work schedules). CONCLUSIONS: Respondents viewed injectable PrEP trial participation as a positive experience and a means of enhancing wellbeing. Study site flexibility and affirming clinic environments, inclusive of non-judgemental counselling, were key facilitators of adherence. To support injection persistence, interventions that address structural barriers and promote flexible means of injection delivery may be most effective.

AAV-delivered hepato-adrenal cooperativity in steroidogenesis: Implications for gene therapy for congenital adrenal hyperplasia.

Despite the availability of life-saving corticosteroids for 70 years, treatment for adrenal insufficiency is not able to recapitulate physiological diurnal cortisol secretion and results in numerous complications. Gene therapy is an attractive possibility for monogenic adrenocortical disorders such as congenital adrenal hyperplasia; however, requires further development of gene transfer/editing technologies and knowledge of the target progenitor cell populations. Vectors based on adeno-associated virus are the leading system for direct in vivo gene delivery but have limitations in targeting replicating cell populations such as in the adrenal cortex. One strategy to overcome this technological limitation is to deliver the relevant adrenocortical gene to a currently targetable organ outside of the adrenal cortex. To explore this possibility, we developed a vector encoding human 21-hydroxylase and directed expression to the liver in a mouse model of congenital adrenal hyperplasia. This extra-adrenal expression resulted in reconstitution of the steroidogenic pathway. Aldosterone and renin levels normalized, and corticosterone levels improved sufficiently to reduce adrenal hyperplasia. This strategy could provide an alternative treatment option for monogenic adrenal disorders, particularly for mineralocorticoid defects. These findings also demonstrate, when targeting the adrenal gland, that inadvertent liver transduction should be precluded as it may confound data interpretation.

Incidence and Predictors of Tuberculosis-associated IRIS in People With HIV Treated for Tuberculosis: Findings From Reflate TB2 Randomized Trial.

Background: After antiretroviral therapy (ART) initiation, people with HIV (PWH) treated for tuberculosis (TB) may develop TB-associated immune reconstitution inflammatory syndrome (TB-IRIS). Integrase inhibitors, by providing a faster HIV-RNA decline than efavirenz, might increase the risk for this complication. We sought to assess incidence and determinants of TB-IRIS in PWH with TB on raltegravir- or efavirenz-based ART. Methods: We conducted a secondary analysis of the Reflate TB 2 trial, which randomized ART-naive PWH on standard TB treatment, to receive raltegravir- or efavirenz-based ART. The primary objective was to evaluate the incidence of TB-IRIS. Incidence rate ratio comparing TB-IRIS incidence in each arm was calculated. Kaplan-Meier curves were used to compare TB-IRIS-free survival probabilities by ART arm. Cox regression models were fitted to analyze baseline characteristics associated with TB-IRIS. Results: Of 460 trial participants, 453 from Brazil, Côte d'Ivoire, Mozambique, and Vietnam were included in this analysis. Baseline characteristics were median age 35 years (interquartile range [IQR], 29-43), 40% female, 69% pulmonary TB only, median CD4, 102 (IQR, 38-239) cells/mm³, and median HIV RNA, 5.5 (IQR, 5.0-5.8) log copies/mL. Forty-eight participants developed TB-IRIS (incidence rate, 24.7/100 PY), 19 cases in the raltegravir arm and 29 in the efavirenz arm (incidence rate ratio 0.62, 95% confidence interval .35-1.10). Factors associated with TB-IRIS were: CD4 ≤ 100 cells/µL, HIV RNA ≥500 000 copies/mL, and extrapulmonary/disseminated TB. Conclusions: We did not demonstrate that raltegravir-based ART increased the incidence of TB-IRIS compared with efavirenz-based ART. Low CD4 counts, high HIV RNA, and extrapulmonary/disseminated TB at ART initiation were associated with TB-IRIS.

A cultural script for suicide among White men in the Mountain West Region of the United States.

The states of the Mountain West region of the United States consistently have the highest rates of suicide in the country, a pattern particularly pronounced in older White men. Although multiple constructs have been proposed to explain this long-standing pattern, including social isolation, cultural values, and psychopathology, relatively little research has been conducted to directly examine the predictive role of these risk factors and how they interact. We review the extant research for these constructs to establish (a) whether the risk factor occurs at a higher rate or is otherwise more influential in this region compared to the rest of the country and (b) whether the risk factor may account for specific effects in older White men in order to determine whether the evidence supports the role of each risk factor in understanding the high rates of suicide among older White men in this region. Using the results of this review, we then present a possible cultural script for suicide based on cultural scripts of gender and suicide theory (Canetto, 1997, 2017, 2021) that describes who dies by suicide, the methods they use, their emotions and motives, and the cultural understanding of the causes and acceptability of their suicidal behaviors within the Mountain West. This cultural script can serve as a guide for researchers investigating the complex mechanisms that account for elevated rates of suicide in this region. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Knowledge of HIV transmission, prevention strategies and U = U among adult sexual and gender minorities in Brazil.

INTRODUCTION: Although strong scientific evidence of the efficacy and effectiveness of treatment-as-prevention (TasP) is available, full endorsement of the "Undetectable = Untransmittable" (U = U) and "zero-risk" messages could be improved. Increasing knowledge about HIV transmission, prevention and treatment is a critical component of care efforts. The study assessed knowledge of HIV transmission and prevention strategies, and the perceived accuracy of the slogan U = U among sexual and gender minorities (SGM) in Brazil. METHODS: Cross-sectional web-based survey targeting adult SGM living in Brazil (2021-2022) recruited on social media and dating apps. We used the 12-item HIV Knowledge Assessment (HIV-KA) questionnaire to assess HIV knowledge, three items of which address pre-exposure prophylaxis (PrEP), post-exposure prophylaxis and TasP. Perceived accuracy of the U = U slogan was assessed with the question: "With regards to HIV-positive individuals transmitting HIV through sexual contact, how accurate do you believe the slogan U = U is?". We a priori grouped the study population into three mutually exclusive groups: people living with HIV (PLHIV), HIV negative and HIV unknown. We used logistic regression models to assess factors associated with high HIV knowledge and perception of the U = U as completely accurate. RESULTS: Of 50,222 individuals accessing the questionnaire, 23,981 were included: 5071 (21.0%) PLHIV, 17,257 (71.5%) HIV negative and 1653 (6.9%) HIV unknown. The proportion of participants with high knowledge was significantly higher for PLHIV and HIV negative (48.1% and 45.5%, respectively) compared to 26.1% of HIV unknown. More PLHIV perceived U = U as completely accurate (80.4%), compared to 60.0% of HIV negative and 42.9% of HIV unknown. HIV knowledge correlates with perceived accuracy of the U = U slogan across all groups. Higher HIV knowledge was associated with higher income and education regardless of HIV status. Among HIV-negative participants, PrEP awareness and use were associated with higher knowledge and accurate perception of the U = U slogan. CONCLUSIONS: Our findings show that HIV knowledge and perceived accuracy of U = U are strongly correlated, that knowledge differs according to HIV status, and that poor socio-economic is linked to poor knowledge among SGM from Brazil. Educational strategies regarding TasP, U = U and zero risk targeting socio-economically vulnerable populations are urgent in Brazil.

Safety of the yellow fever vaccine in people living with HIV: a longitudinal study exploring post-vaccination viremia and hematological and liver kinetics.

BACKGROUND: Safety data on the yellow fever vaccine 17DD in People Living with HIV (PLWH) are limited. This study explored the occurrence of post-vaccination 17DD viremia and the kinetics of hematological and liver laboratorial parameters in PLWH and HIV-uninfected participants [HIV(-) controls]. METHODS: We conducted a secondary analysis of a longitudinal interventional trial (NCT03132311) study that enrolled PLWH and HIV(-) controls to receive a single 17DD dose and were followed at 5, 30 and 365 days after vaccination in Rio de Janeiro, Brazil. 17DD viremia (obtained throughreal-time PCR and plaque forming units' assays), hematological (neutrophils, lymphocytes and platelets counts) and liver enzymes (ALT and AST) results were assessed at baseline and Days 5 and 30 post-vaccination. Logistic regression models explored factors associated with the odds of having positive 17DD viremia. Linear regression models explored variables associated with hematological and liver enzymes results at Day 5. RESULTS: A total of 202 PLWH with CD4 ≥ 200 cells/µL and 68 HIV(-) controls were included in the analyses. 17DD viremia was found in 20.0 % of the participants and was twice more frequent in PLWH than in HIV(-) controls (22.8% vs. 11.8 %, p-value < 0.001). Neutrophils, lymphocytes and platelets counts dropped at Day 5 and returned to baseline values at Day 30. 17DD viremia was associated with lower nadir of lymphocytes and platelets at Day 5. ALT levels did not increase post-vaccination and were not associated with 17DD viremia. CONCLUSIONS: 17DD was safe and well-tolerated in PLWH with CD4 ≥ 200 cells/µL. Post-vaccination viremia was more frequent in PLWH than in controls. Transient and self-limited decreases in lymphocytes and neutrophils occurred early after vaccination. 17DD viremia was associated with lower lymphocytes and platelets nadir after vaccination. We did not observe elevations in ALT after 17DD vaccination.

Antimicrobial activity of hydralazine against methicillin-resistant and methicillin-susceptible Staphylococcus aureus.

Background: Staphylococcus aureus is a human pathogen responsible for high mortality rates. The development of new antimicrobials is urgent. Materials & methods: The authors evaluated the activity of hydralazine along with its synergism with other drugs and action on biofilms. With regard to action mechanisms, the authors evaluated cell viability, DNA damage and molecular docking. Results: MIC and minimum bactericidal concentration values ranged from 128 to 2048 µg/ml. There was synergism with oxacillin (50%) and vancomycin (25%). Hydralazine reduced the viability of biofilms by 50%. After exposure to hydralazine 2× MIC, 58.78% of the cells were unviable, 62.07% were TUNEL positive and 27.03% presented damage in the comet assay (p < 0.05). Hydralazine showed affinity for DNA gyrase and TyrRS. Conclusion: Hydralazine is a potential antibacterial.

Staphylococcus aureus is a bacterium that can cause infection. Infections of S. aureus are becoming difficult to treat, but developing new drugs is a challenge. Repurposing them may be easier. This study looks at the possibility of using hydralazine, a type of medicine used to treat high blood pressure, against S. aureus. The authors found that hydralazine can kill S. aureus and can be used with other antibiotics, including oxacillin and vancomycin. Hydralazine interferes with important processes for the multiplication and survival of this bacterium. These results are preliminary but encouraging. Further studies are needed to confirm the use of hydralazine as a new treatment for S. aureus infections.

Does Including Facebook Training Improve the Effectiveness of Computerized Cognitive Training? A Randomized Controlled Trial.

OBJECTIVE: To determine whether implementing a Facebook training program improves the effectiveness of computerized cognitive training (CCT) in older adults. DESIGN: Randomized, controlled, double single-blind trial with parallel groups. SETTING: Community centers. SUBJECTS: Eighty-six adults between 60 and 90 years old. INTERVENTIONS: Nine face-to-face 60-min sessions of CCT with VIRTRAEL for all participants. The experimental group received an additional 30 min of Facebook training per session. MAIN MEASURES: Attention (d2 Test of Attention); learning and verbal memory (Hopkins Verbal Learning Test-Revised); working memory (Letter-Number Sequencing test), semantic and abstract reasoning (Similarities and Matrix Reasoning tests); and planning (Key Search test). RESULTS: There was a significant Group*Time interaction in the Hopkins Verbal Learning Test-Revised-Trial 3, Letter-Number sequencing, and Matrix tests. Between groups, post-hoc analyses showed a difference in Matrix reasoning (p < .001; d = 0.893) at post-intervention in favor of the experimental group. Significant main effects of time were found in the CCT group between baseline and 3-month follow-up for Concentration (F = 26.431, p ≤ .001), Letters and Numbers (F = 30.549, p ≤ .001), Learning (F = 38.678, p ≤ .001), Similarities (F = 69.885, p ≤ .001), Matrix (F = 90.342, p ≤ .001), and Key Search (F = 7.904, p = .006) tests. CONCLUSIONS: The utilization of CCT with VIRTRAEL, a freely accessible tool with broad applicability, resulted in enhanced attention, verbal learning, working memory, abstract and semantic reasoning, and planning among older adults. These improvements were sustained for at least three months post-training. Additional training in Facebook did not enhance the effectiveness of CCT.

Epigenetic disruption of the RARγ complex impairs its function to bookmark AR enhancer interactions required for enzalutamide sensitivity in prostate cancer.

The current study in prostate cancer (PCa) focused on the genomic mechanisms at the cross-roads of pro-differentiation signals and the emergence of lineage plasticity. We explored an understudied cistromic mechanism involving RARγ's ability to govern AR cistrome-transcriptome relationships, including those associated with more aggressive PCa features. The RARγ complex in PCa cell models was enriched for canonical cofactors, as well as proteins involved in RNA processing and bookmarking. Identifying the repertoire of miR-96 bound and regulated gene targets, including those recognition elements marked by m6A, revealed their significant enrichment in the RARγ complex. RARγ significantly enhanced the AR cistrome, particularly in active enhancers and super-enhancers, and overlapped with the binding of bookmarking factors. Furthermore, RARγ expression led to nucleosome-free chromatin enriched with H3K27ac, and significantly enhanced the AR cistrome in G2/M cells. RARγ functions also antagonized the transcriptional actions of the lineage master regulator ONECUT2. Similarly, gene programs regulated by either miR-96 or antagonized by RARγ were enriched in alternative lineages and more aggressive PCa phenotypes. Together these findings reveal an under-investigated role for RARγ, modulated by miR-96, to bookmark enhancer sites during mitosis. These sites are required by the AR to promote transcriptional competence, and emphasize luminal differentiation, while antagonizing ONECUT2.

Brief Report: HIV Pre-Exposure Prophylaxis Awareness and Use Among Adolescents in Kenya.

BACKGROUND: HIV pre-exposure prophylaxis (PrEP) is an effective prevention tool; however, use among adolescents is thought to be low. To determine the unmet need and opportunity to expand use, we assessed awareness, prior use, and willingness to take PrEP among Kenyan adolescents. METHODS: The Maneno Yetu study recruited a community-based sample of adolescents aged 15-19 years (N = 3061) in Kisumu for a survey using respondent-driven sampling. RESULTS: Overall, 50% of adolescents had heard of PrEP and 2% had used PrEP. Girls were more likely than boys to have heard of PrEP (53.4% vs. 45.1%; P < 0.001) and used PrEP (3.6% vs. 0.3%; P < 0.001). Among participants, 14% engaged in transactional sex and 21% experienced forced sexual contact. PrEP use was higher among adolescents who engaged in transactional sex (4.8% vs. 0.6%; P < 0.001) and experienced forced sexual contact (2.7% vs. 0.7%; P < 0.001) compared with those who did not. Among adolescents with no prior use, 53% were willing to consider using PrEP, although girls were less willing than boys (49.7% vs. 55.9%; P = 0.001). CONCLUSIONS: PrEP is an important prevention tool, especially for adolescents whose circumstances potentially expose them to HIV-positive or unknown status sexual partners, yet remains underused, particularly in resource-limited settings. Although many expressed willingness to use PrEP, low awareness and use highlight the need to expand HIV prevention education and services tailored for adolescents. Our finding that boys were more willing to use PrEP suggests campaigns should also be designed to reach male youth to narrow the gender gap and expand uptake in the adolescent population.

Motor performance and functional connectivity between the posterior cingulate cortex and supplementary motor cortex in bipolar and unipolar depression.

Although implicated in unsuccessful treatment, psychomotor deficits and their neurobiological underpinnings in bipolar (BD) and unipolar (UD) depression remain poorly investigated. Here, we hypothesized that motor performance deficits in depressed patients would relate to basal functional coupling of the hand primary motor cortex (M1) and the posterior cingulate cortex (PCC) with the supplementary motor area (SMA). We performed a longitudinal, naturalistic study in BD, UD and matched healthy controls comprising of two resting-state functional MRI measurements five weeks apart and accompanying assessments of motor performance using a finger tapping task (FTT). A subject-specific seed-based analysis describing functional connectivity between PCC-SMA as well as M1-SMA was conducted. The basal relationships with motor performance were investigated using linear regression models and all measures were compared across groups. Performance in FTT was impaired in BD in comparison to HC in both sessions. Behavioral performance across groups correlated significantly with resting state functional coupling of PCC-SMA, but not of M1-SMA regions. This relationship was partially reflected in a reduced PCC-SMA connectivity in BD vs HC in the second session. Exploratory evaluation of large-scale networks coupling (SMN-DMN) exhibited no correlation to motor performance. Our results shed new light on the association between the degree of disruption in the SMA-PCC anticorrelation and the level of motor impairment in BD.

Safety of the yellow fever vaccine in people living with HIV: a longitudinal study exploring post-vaccination viremia and hematological and liver kinetics

ABSTRACT Background: Safety data on the yellow fever vaccine 17DD in People Living with HIV (PLWH) are limited. This study explored the occurrence of post-vaccination 17DD viremia and the kinetics of hematological and liver laboratorial parameters in PLWH and HIV-uninfected participants [HIV(-) controls]. Methods: We conducted a secondary analysis of a longitudinal interventional trial (NCT03132311) study that enrolled PLWH and HIV(-) controls to receive a single 17DD dose and were followed at 5, 30 and 365 days after vaccination in Rio de Janeiro, Brazil. 17DD viremia (obtained throughreal-time PCR and plaque forming units' assays), hematological (neutrophils, lymphocytes and platelets counts) and liver enzymes (ALT and AST) results were assessed at baseline and Days 5 and 30 post-vaccination. Logistic regression models explored factors associated with the odds of having positive 17DD viremia. Linear regression models explored variables associated with hematological and liver enzymes results at Day 5. Results: A total of 202 PLWH with CD4 > 200 cells/μL and 68 HIV(-) controls were included in the analyses. 17DD viremia was found in 20.0 % of the participants and was twice more frequent in PLWH than in HIV(-) controls (22.8% vs. 11.8 %, p-value < 0.001). Neutrophils, lymphocytes and platelets counts dropped at Day 5 and returned to baseline values at Day 30. 17DD viremia was associated with lower nadir of lymphocytes and platelets at Day 5. ALT levels did not increase post-vaccination and were not associated with 17DD viremia. Conclusions: 17DD was safe and well-tolerated in PLWH with CD4 > 200 cells/μL. Post-vaccination viremia was more frequent in PLWH than in controls. Transient and self-limited decreases in lymphocytes and neutrophils occurred early after vaccination. 17DD viremia was associated with lower lymphocytes and platelets nadir after vaccination. We did not observe elevations in ALT after 17DD vaccination.

Travessia na Terceira Margem - Um dispositivo clínico fora do padrão / Travessia on the Third Bank - A non-standard clinical device

Apresentamos o Projeto Travessia, analisando uma situação clínica grupal de elaboração-luto, em que foram utilizados diversos dispositivos estéticos, tendo como centro do trabalho o conto A terceira margem do rio, de Guimarães Rosa. São abordadas as características técnicas e conceituais deste trabalho. Compreendemos que o desenvolvimento de dispositivos sob medida para cada realidade clínica é importante para a prática psicanalítica em situações sociais traumáticas.(AU)

We present the Travessia Project, analyzing a clinical case of grief elaboration in a group intervention, in which several aesthetic devices were used, having as the center the short story A terceira margem do rio, by Guimarães Rosa. The technical and conceptual characteristics of this intervention are addressed. We understand that the development of tailor-made devices for each clinical reality is important for psychoanalytic practice in traumatic social situations.(AU)