Molecular underpinnings of dedifferentiation and aggressiveness in chromophobe renal cell carcinoma.

Sarcomatoid dedifferentiation is common to multiple renal cell carcinoma (RCC) subtypes, including chromophobe RCC (ChRCC), and is associated with increased aggressiveness, resistance to targeted therapies, and heightened sensitivity to immunotherapy. To study ChRCC dedifferentiation, we performed multiregion integrated paired pathological and genomic analyses. Interestingly, ChRCC dedifferentiates not only into sarcomatoid but also into anaplastic and glandular subtypes, which are similarly associated with increased aggressiveness and metastases. Dedifferentiated ChRCC shows loss of epithelial markers, convergent gene expression, and whole genome duplication from a hypodiploid state characteristic of classic ChRCC. We identified an intermediate state with atypia and increased mitosis but preserved epithelial markers. Our data suggest that dedifferentiation is initiated by hemizygous mutation of TP53, which can be observed in differentiated areas, as well as mutation of PTEN. Notably, these mutations become homozygous with duplication of preexisting monosomes (i.e., chromosomes 17 and 10), which characterizes the transition to dedifferentiated ChRCC. Serving as potential biomarkers, dedifferentiated areas become accentuated by mTORC1 activation (phospho-S6) and p53 stabilization. Notably, dedifferentiated ChRCC share gene enrichment and pathway activation features with other sarcomatoid RCC, suggesting convergent evolutionary trajectories. This study expands our understanding of aggressive ChRCC, provides insight into molecular mechanisms of tumor progression, and informs pathologic classification and diagnostics.

Coordinated wound responses in a regenerative animal-algal holobiont.

Animal regeneration involves coordinated responses across cell types throughout the animal body. In endosymbiotic animals, whether and how symbionts react to host injury and how cellular responses are integrated across species remain unexplored. Here, we study the acoel Convolutriloba longifissura, which hosts symbiotic Tetraselmis sp. green algae and can regenerate entire bodies from tissue fragments. We show that animal injury causes a decline in the photosynthetic efficiency of the symbiotic algae, alongside two distinct, sequential waves of transcriptional responses in acoel and algal cells. The initial algal response is characterized by the upregulation of a cohort of photosynthesis-related genes, though photosynthesis is not necessary for regeneration. A conserved animal transcription factor, runt, is induced after injury and required for acoel regeneration. Knockdown of Cl-runt dampens transcriptional responses in both species and further reduces algal photosynthetic efficiency post-injury. Our results suggest that the holobiont functions as an integrated unit of biological organization by coordinating molecular networks across species through the runt-dependent animal regeneration program.

i-shaped antibody engineering enables conformational tuning of biotherapeutic receptor agonists.

The ability to leverage antibodies to agonize disease relevant biological pathways has tremendous potential for clinical investigation. Yet while antibodies have been successful as antagonists, immune mediators, and targeting agents, they are not readily effective at recapitulating the biology of natural ligands. Among the important determinants of antibody agonist activity is the geometry of target receptor engagement. Here, we describe an engineering approach inspired by a naturally occurring Fab-Fab homotypic interaction that constrains IgG in a unique i-shaped conformation. i-shaped antibody (iAb) engineering enables potent intrinsic agonism of five tumor necrosis factor receptor superfamily (TNFRSF) targets. When applied to bispecific antibodies against the heterodimeric IL-2 receptor pair, constrained bispecific IgG formats recapitulate IL-2 agonist activity. iAb engineering provides a tool to tune agonist antibody function and this work provides a framework for the development of intrinsic antibody agonists with the potential for generalization across broad receptor classes.

The Perfect Med Bag is One that Doesn't Fall Off a Cliff: A Combat Mass Casualty Case.

Military trauma provides a unique pattern of injuries due to the high velocity, high kinetic energy ammunition utilized, and the high prevalence of blast injury. To further complicate this, military trauma often occurs in austere environments with limited logistical support. Therefore, military medical providers are forced to learn nonstandard techniques and when necessary, practice a level of improvisation not commonly seen in other medical fields. The case presented in this manuscript is a prime example of these challenges. At the onset of fighting both the medic's rucksack, carrying with it the primary source of medical gear and the precious supply of cold-stored blood products are lost. The scenario was further complicated by rough mountainous terrain and a prolonged evacuation time. The medical provider was forced to utilize nonstandard devices such as an improvised junctional tourniquet which used a rock to focus the devices pressure. They also adapted their basic understanding of surgical procedures to conduct a vascular cutdown procedure for wound exposure and effectively pack an otherwise non-compressible wound to a major artery. Despite a significant loss of equipment, the medic and their team were able to successfully care for a number of patients in this mass casualty scenario.

Systematic discovery of neoepitope-HLA pairs for neoantigens shared among patients and tumor types.

The broad application of precision cancer immunotherapies is limited by the number of validated neoepitopes that are common among patients or tumor types. To expand the known repertoire of shared neoantigen-human leukocyte antigen (HLA) complexes, we developed a high-throughput platform that coupled an in vitro peptide-HLA binding assay with engineered cellular models expressing individual HLA alleles in combination with a concatenated transgene harboring 47 common cancer neoantigens. From more than 24,000 possible neoepitope-HLA combinations, biochemical and computational assessment yielded 844 unique candidates, of which 86 were verified after immunoprecipitation mass spectrometry analyses of engineered, monoallelic cell lines. To evaluate the potential for immunogenicity, we identified T cell receptors that recognized select neoepitope-HLA pairs and elicited a response after introduction into human T cells. These cellular systems and our data on therapeutically relevant neoepitopes in their HLA contexts will aid researchers studying antigen processing as well as neoepitope targeting therapies.

Beyond the Brachial Plexus: Reapplication of the Thoracic Paravertebral Block for Upper Arm Fistula Surgery.

Patients requiring complex upper arm arteriovenous fistulas or grafts may not be suitable candidates for a single regional anesthesia technique and monitored anesthesia care because the necessary thoracic (T2) dermatomal area of the medial, upper arm remains spared by any solitary brachial plexus (C5-T1) technique. An infiltrative intercostobrachial nerve block can often be used in conjunction with a brachial plexus block; however, coverage may still be incomplete. This case report describes the use of a high thoracic paravertebral block in conjunction with a brachial plexus block to achieve adequate anesthetic coverage for an upper arm arteriovenous fistula creation procedure extending into the axilla. The result of this technique showed adequate coverage of the upper arm and demonstrates that paravertebral blocks are a reasonable adjunct for proximal upper arm arteriovenous fistula procedures.

Generation of Schwann cell derived melanocytes from hPSCs identifies pro-metastatic factors in melanoma.

The neural crest (NC) is highly multipotent and generates diverse lineages in the developing embryo. However, spatiotemporally distinct NC populations display differences in fate potential, such as increased gliogenic and parasympathetic potential from later migrating, nerve-associated Schwann cell precursors (SCPs). Interestingly, while melanogenic potential is shared by both early migrating NC and SCPs, differences in melanocyte identity resulting from differentiation through these temporally distinct progenitors have not been determined. Here, we leverage a human pluripotent stem cell (hPSC) model of NC temporal patterning to comprehensively characterize human NC heterogeneity, fate bias, and lineage development. We captured the transition of NC differentiation between temporally and transcriptionally distinct melanogenic progenitors and identified modules of candidate transcription factor and signaling activity associated with this transition. For the first time, we established a protocol for the directed differentiation of melanocytes from hPSCs through a SCP intermediate, termed trajectory 2 (T2) melanocytes. Leveraging an existing protocol for differentiating early NC-derived melanocytes, termed trajectory 1 (T1), we performed the first comprehensive comparison of transcriptional and functional differences between these distinct melanocyte populations, revealing differences in pigmentation and unique expression of transcription factors, ligands, receptors and surface markers. We found a significant link between the T2 melanocyte transcriptional signature and decreased survival in melanoma patients in the cancer genome atlas (TCGA). We performed an in vivo CRISPRi screen of T1 and T2 melanocyte signature genes in a human melanoma cell line and discovered several T2-specific markers that promote lung metastasis in mice. We further demonstrated that one of these factors, SNRPB, regulates the splicing of transcripts involved in metastasis relevant functions such as migration, cell adhesion and proliferation. Overall, this study identifies distinct developmental trajectories as a source of diversity in melanocytes and implicates the unique molecular signature of SCP-derived melanocytes in metastatic melanoma.

Isometric Knee Strength is Greater in Individuals Who Score Higher on Psychological Readiness to Return to Sport After Primary Anterior Cruciate Ligament Reconstruction.

Background: Anterior cruciate ligament (ACL) injury is extremely common among athletes. Rate of second ACL injury due to surgical graft rupture or contralateral limb ACL injury is approximately 15-32%. Psychological readiness to return to sport (RTS) may be an important predictor of successful RTS outcomes. Psychological readiness can be quantified using the ACL Return to Sport after Injury (ACL-RSI) questionnaire, with higher scores demonstrating greater psychological readiness. Purpose: The purpose of this study was to investigate differences in functional performance and psychological readiness to return to sport among athletes who have undergone primary ACL reconstruction (ACLR). Study Design: Descriptive cohort study. Methods: Eighteen athletes who had undergone primary ACLR were tested at time of RTS clearance. The cohort was divided into two groups, high score (HS) and low score (LS), based on median ACL-RSI score, and performance on static and dynamic postural stability testing, lower extremity isokinetic and isometric strength testing, and single leg hop testing was compared between the groups using an independent samples t-test. Results: The median ACL-RSI score was 74.17. The average ACL-RSI score was 83.1±6.2 for the HS group and 61.8±8.0 for the LS group. High scorers on the ACL-RSI performed significantly better on isometric knee flexion as measured via handheld dynamometry (22.61% ±6.01 vs. 12.12% ±4.88, p=0.001) than the low score group. Conclusion: The findings suggest that increased knee flexion strength may be important for psychological readiness to RTS after primary ACLR. Further research is indicated to explore this relationship, however, a continued emphasis on improving hamstring strength may be appropriate during rehabilitation following ACLR to positively impact psychological readiness for RTS. Level of Evidence: III.

Effect of Concussion on Reaction Time and Neurocognitive Factors: Implications for Subsequent Lower Extremity Injury.

Background: Recent evidence has demonstrated that athletes are at greater risk for a lower extremity injury following a return-to-sport (RTS) after sport-related concussion (SRC). The reason for this is not completely clear, but it has been hypothesized that persistent deficits in neurocognitive factors may be a contributing factor. Hypothesis/Purpose: This study assessed simple reaction time, processing speed, attention, and concentration in a group of athletes, post-concussion upon clearance for RTS for potential deficits that may result in slower reaction time, processing speed, attention, and concentration. The researchers hypothesized that the concussion group would demonstrate worse scores on both assessments compared to a sex-, age-, and sport-matched cohort. Study Design: Case-controlled study. Methods: Twelve participants who had suffered a SRC and eight healthy individuals who were matched to the concussed group by age, sex, and sport were evaluated. Those with a concussion had been cleared for RTS by a licensed healthcare provider. Each participant underwent neurocognitive tests that included a simple reaction time test (SRT) and the King-Devick Test (K-D). Independent t-tests were performed to compare the groups with significance set a priori at p<0.05. Results: There was a significant difference (p =0.024) between groups for SRT with the concussed group demonstrating a better SRT than the control group. There were no significant differences (p =0.939) between the groups for the K-D. Conclusion: With no significant differences between groups in the K-D assessment and, surprisingly, the concussed group having a better SRT compared to the healthy group, our hypothesis was not supported. Clinical Relevance: These specific measures, compounded with extensive post-concussion time lapse until RTS clearance, may have limited capacity in revealing potential persistent deficits in relevant neurocognitive characteristics. Level of Evidence: Level of Evidence 3.

Females have Lower Knee Strength and Vertical Ground Reaction Forces During Landing than Males Following Anterior Cruciate Ligament Reconstruction at the Time of Return to Sport.

Purpose: There is a high rate of second anterior cruciate ligament (ACL) injury (ipsilateral graft or contralateral ACL) upon return-to-sport (RTS) following ACL reconstruction (ACLR). While a significant amount of epidemiological data exists demonstrating sex differences as risk factors for primary ACL injury, less is known about sex differences as potential risk factors for second ACL injury. The purpose of this study is to determine if there are sex-specific differences in potential risk factors for second ACL injury at the time of clearance for RTS. Methods: Ten male and eight female athletes (age: 20.8 years ±6.3, height: 173.2 cm ±10.1, mass: 76.6 kg ±18.3) participated in the study following ACLR at time of RTS (mean 10.2 months). Performance in lower extremity isokinetic and isometric strength testing, static and dynamic postural stability testing, and a single leg stop-jump task was compared between the sexes. Results: Normalized for body weight, males had significantly greater isokinetic knee flexion (141±14.1 Nm/kg vs. 78±27.4 Nm/kg, p=0.001) and extension strength (216±45.5 Nm/kg vs. 159±53.9 Nm/kg, p=0.013) as well as isometric flexion (21.1±6.87% body weight vs. 12.5±5.57% body weight, p=0.013) and extension (41.1±7.34% body weight vs. 27.3±11.0% body weight, p=0.016) strength compared to females. In the single-leg stop jump task, males had a greater maximum vertical ground reaction force during landing (332±85.5% vs. 259±27.4% body weight, p=0.027) compared to females. Conclusions: Based on these results, there are significant differences between sexes following ACLR at the time of RTS. Lower knee flexion and extension strength may be a potential risk factor for second ACL injury among females. Alternatively, the increased maximum vertical force observed in males may be a potential risk factor of second ACL injury in males. Although these results should be interpreted with some caution, they support that rehabilitation programs in the post-ACLR population should be individualized based on the sex of the individual. Level of Evidence: Level 3.

Effect of a Popular Web Drama Video Series on HIV and Other Sexually Transmitted Infection Testing Among Gay, Bisexual, and Other Men Who Have Sex With Men in Singapore: Community-Based, Pragmatic, Randomized Controlled Trial.

BACKGROUND: Gay, bisexual, and other men who have sex with men (GBMSM) are at disproportionately higher risk of acquiring HIV and other sexually transmitted infections (STI). While HIV/STI testing rates among GBMSM are increasing worldwide, they remain suboptimal in a variety of settings. While many studies have attempted to evaluate the efficacy of a variety of community-based campaigns, including peer and reminder-based interventions on HIV/STI testing, however few have attempted to do so for a web drama series. OBJECTIVE: This study evaluates the effectiveness of a popular web drama video series developed by a community-based organization in Singapore for GBMSM on HIV and other STI testing behaviors. METHODS: The study is a pragmatic, randomized controlled trial to evaluate a popular web drama video series developed by a community-based organization in Singapore for GBMSM. A total of 300 HIV-negative, GBMSM men in Singapore aged 18 to 29 years old were recruited and block-randomized into the intervention (n=150) and control arms (n=150). Primary outcomes included changes in self-reported intention to test for, actual testing for, and regularity of testing for HIV, syphilis, chlamydia or gonorrhea, while secondary outcomes include changes in a variety of other knowledge-based and psychosocial measures at the end of the study period. RESULTS: Overall, 83.3% (125/150) of participants in the intervention arm completed the proof of completion survey, compared to 88.7% (133/150) in the control arm. We found improvements in self-reporting as a regular (at least yearly) tester for HIV (15.9% difference, 95% CI, 3.2% to 28.6%; P=.02), as well as chlamydia or gonorrhea (15.5% difference, 95% CI, 4.2% to 26.9%; P=.009), indicating that the intervention had positively impacted these outcomes compared to the control condition. We also found improvements in participants' intentions to test for HIV (16.6% difference, 95% CI, 4.3% to 28.9%; P=.009), syphilis (14.8% difference, 95% CI, 3.2% to 26.4%; P=.01), as well as chlamydia or gonorrhea (15.4% difference, 95% CI, 4.2% to 26.6%; P=.008), in the next 3 months, indicating that the intervention was effective in positively impacting intention for HIV and other STI testing among participants. CONCLUSIONS: There are clear benefits for promoting intentions to test regularly and prospectively on a broad scale through this intervention. This intervention also has potential to reach GBMSM who may not have access to conventional HIV and other STI prevention messaging, which have typically been implemented at sex-on-premises venues, bars, clubs, and in sexual health settings frequented by GBMSM. When coupled with community or population-wide structural interventions, the overall impact on testing will likely be significant. TRIAL REGISTRATION: ClinicalTrials.gov NCT04021953; https://clinicaltrials.gov/ct2/show/NCT04021953. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): RR2-10.1136/bmjopen-2019-033855.

Hepatitis B Screening, Vaccination, and Linkage to Care: Lessons Learned from a Mississippi Vietnamese Community.

BACKGROUND: Asian-Americans and Pacific Islanders are disproportionately impacted by chronic hepatitis B infection (CHBI). The long-term effects of untreated CHBI include cirrhosis of the liver, hepatocellular carcinoma, and liver failure. Approximately two-thirds of those living with CHBI are unaware of their HBV status. OBJECTIVES: Plan, implement, and evaluate a culturally and linguistically appropriate screening, vaccination, and linkage-to-care initiative that used Vietnamese-speaking community health workers for care navigation among Vietnamese-Americans residing in the Mississippi coastal counties of Hancock, Harrison, and Jackson. METHODS: The initiative employed a community-based participatory framework to plan and implement the program. An active community advisory board was established and was representative of all the partners that worked together to make the initiative a success.Results and Lessons Learned: Before program implantation, results from focus groups indicated that the Vietnamese community had low knowledge about the risk of CHBI. Additionally, there were no Vietnamese-speaking health care providers, nor primary care providers treating CHBI in the prioritized counties. A total of 505 Vietnamese individuals were screened. One-half were immune by infection (n = 235 [46.5%]), 83 (16.4%) were immune by vaccination, 46 (9.1%) had CHBI, 130 (25.7%) were vaccine naïve, and 40 (7.9%) were undetermined, (n = 130), 101 (77.7%) received the complete three-injection vaccine series. Five new primary care providers now provide treatment for those with CHBI. Cultural competency and community/medical interpreter training were also provided to reduce language barriers during medical encounters. CONCLUSIONS: To ensure success, it is paramount that community input is not only solicited but that partnerships provide a space where the input informs all aspects of the program.

Altered lower extremity biomechanics following anterior cruciate ligament reconstruction during single-leg and double-leg stop-jump tasks: A bilateral total support moment analysis.

BACKGROUND: Injury to the anterior cruciate ligament (ACL) can lead to long-lasting biomechanical alterations that put individuals at risk of a second ACL injury. Examining the total support moment may reveal between- and within-limb compensatory strategies. METHODS: Twenty-six participants who were cleared to return to sport following ACL reconstruction were recruited. Each participant completed the single-leg and double-leg stop jump tasks. These tasks were analyzed using force plates and a 3D motion analysis system. The total support moment was calculated by summing the internal moments of the hip, knee and ankle at peak vertical ground reaction force. FINDINGS: Internal knee extensor moment was lower in the involved limb compared to the uninvolved for both tasks (17.6%, P = 0.022; 18.4%, P = 0.008). No significant between-limb differences were found for the total support moment. The involved limb exhibited an 18.2% decrease in knee joint contribution (P = 0.01) and a 21.6% increase in ankle joint contribution (P = 0.016) to the total support moment compared to the uninvolved limb in the single-leg stop jump task. INTERPRETATION: Compensation for the involved knee is likely due to altered biomechanics that redistributes load to the uninvolved knee or to adjacent joints of the same limb. A partial shift in joint contribution from the knee to the ankle during the single-leg stop jump task demonstrates a tendency to decrease load to the knee. Further studies are needed to investigate how these adaptations impact the prevalence of subsequent injury and poor joint health.

Human melanocyte development and melanoma dedifferentiation at single-cell resolution.

In humans, epidermal melanocytes are responsible for skin pigmentation, defence against ultraviolet radiation and the deadliest common skin cancer, melanoma. Although there is substantial overlap in melanocyte development pathways between different model organisms, species-dependent differences are frequent and the conservation of these processes in human skin remains unresolved. Here, we used a single-cell enrichment and RNA-sequencing pipeline to study human epidermal melanocytes directly from the skin, capturing transcriptomes across different anatomical sites, developmental age, sexes and multiple skin tones. We uncovered subpopulations of melanocytes that exhibit anatomical site-specific enrichment that occurs during gestation and persists through adulthood. The transcriptional signature of the volar-enriched subpopulation is retained in acral melanomas. Furthermore, we identified human melanocyte differentiation transcriptional programs that are distinct from gene signatures generated from model systems. Finally, we used these programs to define patterns of dedifferentiation that are predictive of melanoma prognosis and response to immune checkpoint inhibitor therapy.

Experienced Homophobia and Suicide Among Young Gay, Bisexual, Transgender, and Queer Men in Singapore: Exploring the Mediating Role of Depression Severity, Self-Esteem, and Outness in the Pink Carpet Y Cohort Study.

Purpose: No prior study has been published on suicide-related behaviors among gay, bisexual, transgender, and queer (GBTQ) men in Singapore, where sexual relations between men are criminalized. This study explores the association and mediational pathways between experienced homophobia and suicidal ideation or suicide attempts among young GBTQ men in Singapore. Methods: Results of this study were derived from baseline data of the Pink Carpet Y Cohort Study, Singapore's first prospective cohort study among young GBTQ men. The sample comprised 570 young GBTQ men 18 to 25 years of age who were HIV negative or unsure of their HIV status. Statistical analyses were conducted through descriptive statistics, multivariable logistic regression, and structural equation modeling techniques. Results: Of 570 participants, 58.9% (n = 308) reported ever contemplating suicide, whereas 14.2% (n = 76) had ever attempted suicide. Controlling for key demographic variables, multivariable logistic regression revealed that experienced homophobia and depression severity were positively associated with a history of suicidal ideation, whereas depression severity and outness were positively associated with a history of suicide attempts. Mediation analyses revealed that depression severity and self-esteem partially accounted for the relationship between experienced homophobia and suicidal ideation, whereas depression severity and outness partially accounted for the relationship with suicide attempts. Conclusions: The prevalence of suicidal ideation and past suicide attempts was found to be high in a sample of young GBTQ men in Singapore. Interventions to address experienced homophobia and discrimination among young GBTQ men are needed urgently in Singapore.

Delineating patterns of sexualized substance use and its association with sexual and mental health outcomes among young gay, bisexual and other men who have sex with men in Singapore: a latent class analysis.

BACKGROUND: Young gay, bisexual, and other men who have sex with men (YMSM) are vulnerable to the risks associated with sexualized substance use. This is a novel study in Singapore that aims to classify patterns of sexualized substance use among YMSM, and investigate its association with sexual and mental health outcomes. METHODS: In this cross-sectional study among 570 YMSM aged 18 to 25 years old, latent class analysis (LCA) conducted to identify classes with similar patterns of sexualized substance use, across which measures of inconsistent condom use, recent STI diagnoses, past suicide ideation and depression severity were compared. RESULTS: LCA revealed three classes of YMSM based on types of substances ever used in sexualized contexts, which we labelled as 'substance-naive', 'substance-novice', and 'chemsex'. Substance-naive participants (n = 404) had only ever used alcohol, while substance-novice participants (n = 143) were primarily amyl nitrite users with a small proportion who reported using chemsex-related drugs. Chemsex participants (n = 23) comprised individuals who had mostly used such drugs. Those in the chemsex group were more likely to report recent unprotected anal sex with casual partners (aPR = 3.28, 95%CI [1.85, 5.79]), depression severity (aß = 3.69, 95%CI [0.87, 6.51]) and a history of suicide ideation (aPR = 1.64, 95%CI [1.33, 2.03]). CONCLUSIONS: Findings of this study highlight how the use of varying substances in sexualized contexts may be classified and characterized by different sexual and mental health outcomes. Health promotion efforts should be differentiated accordingly to address the risks associated with sexualized substance use among YMSM.

Two year follow up of supercapsular percutaneously assisted total hip arthroplasty.

BACKGROUND: Dislocation after primary total hip arthroplasty (THA) has an incidence of 2-3%. Approximately 77% of dislocations occur within the first year after surgery. The SuperPATH technique is a minimally invasive approach for THA that preserves soft tissue attachments. The purpose of this study is to describe the dislocation rate at 1 year after SuperPATH primary THA. METHODS: All elective primary THAs performed by the senior author using the SuperPATH approach. Exclusion criteria were acute femoral neck fracture, revision surgery, or malignancy. There were 214 of 279 eligible patients available for telephone interviews (76.7%). Medical records were reviewed for secondary outcomes including early and late complications, cup positioning, distance ambulated on postoperative day one, discharge destination, and blood transfusions. RESULTS: Mean age at surgery was 64 ± 10.8 years and mean time to telephone follow up was 773 ± 269.7 days. There were 104 female and 110 male patients. There were zero dislocations reported. Blood transfusions were performed in 3.7% of patients, and 75.7% were discharged to home at an average of 2.3 ± 1.0 days. Cup position averaged 43.6 ± 5.2° abduction and 20.9 ± 6.2° anteversion, with an average leg length discrepancy of 3.6 ± 3.32 mm. Complications included three intraoperative calcar fractures, one periprosthetic femur fracture, one early femoral revision, three superficial infections, and one instance of wound necrosis. CONCLUSION: SuperPATH approach is safe for use in primary THA resulting in a low dislocation rate.

Association between sexual orientation acceptance and suicidal ideation, substance use, and internalised homophobia amongst the pink carpet Y cohort study of young gay, bisexual, and queer men in Singapore.

BACKGROUND: Gay, bisexual and queer (GBQ) men are frequently subjected to minority stressors that have negative impacts on their health. Milestones that include the acceptance and disclosure of sexual identity amongst GBQ men are hence key instruments in understanding the prevalence of internalised homophobia and predicting health outcomes. As such, this work takes a novel approach to deduce the correlates of delayed acceptance of sexual orientation in young GBQ men as a measure of internalised homophobia through retrospective self-reporting and age-based analysis. METHODS: Participants were recruited as part of a cohort study exploring the syndemic risks associated with HIV acquisition among young GBQ men in Singapore. We examined their levels of internalised, perceived, experienced homophobia, as well as their health behaviours and suicidal tendencies. Two separate variables were also self-reported by the participants - the age of questioning of sexual orientation and the age of acceptance of sexual orientation. We subsequently recoded a new variable, delayed acceptance of sexual orientation, by taking the difference between these two variables, regressing it as an independent and dependent variable to deduce its psychosocial correlates, as well as its association with other measured instruments of health. RESULTS: As a dependent variable, delayed acceptance of sexual orientation is positively associated with an increase of age and internalised homophobia, while being negatively associated with reporting as being gay, compared to being bisexual or queer. As an independent variable, delayed acceptance of sexual orientation was associated with a delayed age of coming out to siblings and parents, suicide ideation, historical use of substances including smoking tobacco cigarettes and consuming marijuana, as well as reporting higher levels of experienced, internalised and perceived homophobia. CONCLUSION: Greater levels of early intervention and efforts are required to reduce the heightened experience of minority stress resulting from communal and institutional hostilities. Areas of improvement may include community-based counselling and psychological support for GBQ men, while not forsaking greater education of the social and healthcare sectors. Most importantly, disrupting the stigma narrative of a GBQ 'lifestyle' is paramount in establishing an accepting social environment that reduces the health disparity faced by GBQ men.

Social capital and chemsex initiation in young gay, bisexual, and other men who have sex with men: the pink carpet Y cohort study.

BACKGROUND: Young gay, bisexual, and other men who have sex with men (YMSM) are especially vulnerable to the risks associated with sexualized substance use, or 'chemsex'. Engaging in chemsex established as a major risk factor for Human Immunodeficiency Virus (HIV) acquisition, and is thus a public health issue of increasing urgency. This paper attempts to explore the association between measures of social capital and patterns of sexualized substance use among a sample of YMSM in Singapore. METHODS: Results of this study were derived from baseline data of the Pink Carpet Y Cohort Study in Singapore, comprising a sample of 570 HIV-negative YMSM aged 18 to 25 years old. Latent class analysis was employed to identify classes with similar patterns of sexualized substance use, and multinomial logistic regression was employed to examine associations between class membership and proxy measures of social capital, including age of sexual debut, bonding and bridging social capital, connectedness to the lesbian, gay, bisexual and transgender community, and outness. RESULTS: Latent class analysis revealed three classes of YMSM based on their histories of sexualized substance use, which we labelled as 'alcohol', 'poppers', and 'chemsex'. Multivariable analyses revealed that participants who were older (aOR = 1.19, p = 0.002) and who identified as gay (aOR = 2.43, p = 0.002) were more likely to be in the poppers class compared to the alcohol class. Participants with a later age of sexual debut were increasingly less likely to be in the poppers (aOR = 0.93, p = 0.039) and chemsex classes (aOR = 0.85, p = 0.018), compared to the alcohol class. CONCLUSIONS: Varying measures of social capital such as an earlier age of exposure to sexual networks may predispose YMSM to greater opportunities for sexualized substance use. Future interventions should target YMSM who become sexually active at an earlier age to reduce the risks associated with sexualized substance use.