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OBJECTIVES: We assessed differences in HIV prevalence and sexual risk behavior among men who have sex with men (MSM) between 1997 and 2002 in San Francisco. METHODS: We used 2 population-based random-digit-dial telephone surveys of MSM households in San Francisco in 1997 (n=915) and 2002 (n=879). RESULTS: Estimated HIV prevalence increased from 19.6% in 1997 to 26.8% in 2002. Measures of sexual risk also increased. Unprotected anal intercourse with a partner of different or unknown HIV serostatus increased from 9.3% to 14.6%. Mean number of male partners increased from 10.7 to 13.8. The largest reported increase was 18.9% to 26.8% for 'serosorting,' or choosing unprotected anal intercourse partners believed to have the same HIV serostatus as oneself. Men aged 30 to 50 reported the largest increase in unprotected anal intercourse, whereas men aged 18 to 29 reported the largest increase in serosorting. Changes in the age distribution did not explain the increase in risky behavior. CONCLUSIONS: Both HIV prevalence and sexual risk increased substantially among MSM in San Francisco between 1997 and 2002. Serosorting is being adopted more frequently than condom use by young MSM, but its effectiveness as a harm reduction strategy is not known. [ABSTRACT FROM AUTHOR]

OBJECTIVES: This study investigated the limitations of probability samples of men who have sex with men (MSM), limited to single cities and to the areas of highest concentrations of MSM ('gay ghettos'). METHODS: A probability sample of 2881 MSM in 4 American cities completed interviews by telephone. RESULTS: MSM who resided in ghettos differed from other MSM, although in different ways in each city. Non-ghetto-dwelling MSM were less involved in the gay and lesbian community. They were also less likely to have only male sexual partners, to identify as gay, and to have been tested for HIV. CONCLUSIONS: These differences between MSM who live in gay ghettos and those who live elsewhere have clear implications for HIV prevention efforts and health care planning. [ABSTRACT FROM AUTHOR]

OBJECTIVES: This study characterized the AIDS epidemic among urban men who have sex with men (MSM). METHODS: A probability sample of MSM was obtained in 1997 (n = 2881; 18 years and older) from New York, Los Angeles, Chicago, and San Francisco, and HIV status was determined through self-report and biological measures. RESULTS: HIV prevalence was 17% (95% confidence interval = 15%, 19%) overall, with extremely high levels in African Americans (29%), MSM who used injection drugs (40%), 'ultraheavy' noninjection drug users (32%), and less educated men (< high school, 37%). City-level HIV differences were non-significant once these other factors were controlled for. In comparing the present findings with historical data based on public records and modeling, HIV prevalence appears to have declined as a result of high mortality (69%) and stable, but high, incidence rates (1%-2%). CONCLUSIONS: Although the findings suggest that HIV prevalence has declined significantly from the mid-1980s, current levels among urban MSM in the United States approximate those of sub-Saharan countries (e.g., 14%-25%) and are extremely high in many population subsegments. Despite years of progress, the AIDS epidemic continues unabated among subsegments of the MSM community. [ABSTRACT FROM AUTHOR]

This analysis was undertaken to identify (a) the level of HIV sexual risk behaviors of men who drop out of treatment and (b) baseline variables associated with later treatment dropout. A cross-sectional sample of 340 gay/bisexual men were recruited from an outpatient substance abuse treatment facility in San Francisco. We compared participants who completed less than 15 visits with participants who graduated from the program. Men who dropped out were more likely than treatment graduates to report injection drug use, social problems related to substance use, self-blaming coping strategies, and more recent substance use prior to entering treatment and less likely to have a college degree, report using sex for tension relief, and have previously attended Alcoholics Anonymous or Narcotics Anonymous. Given the strong link between the substance abuse and HIV epidemics, substance abuse treatment agencies have been forced into addressing the issues of HIV sexual risk taking with their clients. Strategies toward reducing substance use relapse and HIV risk reduction are offered. [ABSTRACT FROM AUTHOR]

A sample of San Francisco gay/bisexual men in substance-abuse treatment (N=314) was compared to the San Francisco Men's Health Study (SFMHS) cohort to compare levels of sexual behaviors that are high-risk for HIV transmission. Quantitative data were supplemented by analysis of transcripts of focus group discussions with gay men in treatment at the same agency. Sexual risk for HIV infection was significantly higher for gay/bisexual men in substance-abuse treatment than among the community-based (SFMHS) sample of gay/bisexual men. Among those entering outpatient alcohol/drug treatment, 21% reported unprotected insertive anal sex, 23% reported unprotected receptive anal sex, and 32% reported unprotected insertive and/or receptive anal sex during the previous 3 months. In comparison, in the SFMHS cohort, 17% reported unprotected insertive anal sex, 15% reported unprotected receptive anal sex, and 22% reported unprotected insertive and/or receptive anal sex during the previous 6 months. Substance abusers in focus groups identified a number of factors that made it difficult to reduce their sexual risk behavior, including the perceived disinhibiting effects of alcohol and other drugs, learned patterns of association between substance use and sex (especially methamphetamine use and anal sex), low self-esteem, lack of assertiveness and negotiating skills, and perceived powerlessness. [ABSTRACT FROM AUTHOR]

We explored the prevalence of childhood sexual abuse among adult gay and bisexual men and measured the association between childhood sexual abuse and high-risk sexual behavior in adulthood. Two separate population-based samples of gay and bisexual men (n = 1,941) residing in Portland and Tucson were surveyed. Over one quarter reported a history of childhood sexual abuse (sexual behavior with someone at least 5 years older prior to age 13, or with someone at least 10 years older when between ages 13 and 15). Men who were abused were more likely to engage in sexual risk behavior than men who were not abused (e.g., unprotected anal intercourse with non-primary partners in the previous 12 months: 21.4% vs. 15.0%, p < .001). Perception of having been coerced was associated with greater sexual risk. Furthermore, childhood sexual abuse and level of coercion were associated with reported levels of HIV infection among gay and bisexual men. It is recommended that existing programs for those at risk for HIV be modified to deal with these issues, and that efforts to bring about behavior change will require approaches that go beyond simply increasing knowledge and awareness. [ABSTRACT FROM AUTHOR]

Observations in the field of lower limb prosthetic rehabilitation have shown that several transfemoral prostheses show signs of wear on some components of the knee unit. This is thought to be a result of severe loading developed during activities associated with kneeling. Some prostheses may have failed due to repetitive action of such loading. In order to determine the nature and magnitude of the loads developed during kneeling by persons with transfemoral amputation, and to investigate the influence of various prosthetic parameters, an analysis of the results of 162 tests in prosthetic knee hyperflexion was undertaken. The services of four males with amputation were enlisted. The measurements involved simultaneous use of two Kistler force platforms, a six-channel strain gauge transducer mounted on the prosthetic shank, and a data acquisition system. The critical loads for this configuration were found to be the shear force on the knee hinge, the shear force imposed by the knee chassis on the shin, and the bending moment tending to hyperflex the knee. These loads ranged from 0.6 to 6.2 kN, 0.9 to 6.7 kN, and from 18.3 to 155.7 Nm, respectively. To achieve a comfortable kneeling position, some prostheses permit foot rotation about the pylon axis of 90 degrees to allow the shank to be approximately parallel to the ground. Tests were also conducted with the prostheses in this configuration and the most influential prosthetic parameter was found to be the external rotation of the foot (toe-out angle). During kneeling, it was found that the loading was dependent upon the position of the torso relative to the prosthesis, but loads were much higher than those developed during level walking. [ABSTRACT FROM AUTHOR]

Detecting H 2 S in oxygen-deficient conditions is vital for identifying leaks in SF 6 -insulated electrical equipment. Current infrared-based detection methods are expensive and sensitive to environmental conditions, highlighting the necessity for cost-effective and stable gas sensors. Existing gas sensors based on semiconducting metal oxides (SMOXs) are limited by redox reactions with oxygen and require high operating temperatures. Here, we introduce a room-temperature (RT) H 2 S sensor for oxygen-deficient environments using the intrinsic conducting two-dimensional (2D) metal-organic framework (MOF), Co 1.8 Ni 1.2 (hexaiminotriphenylene) 2 [Co 1.8 Ni 1.2 (HITP) 2 ], overcoming the limitations of SMOX gas sensors. Remarkably, Co 1.8 Ni 1.2 (HITP) 2 sensors exhibit exceptional selectivity for H 2 S with negligible cross-responses and a sensitivity drift of less than 4.13% in an SF 6 atmosphere over 60 days. The Co 1.8 Ni 1.2 (HITP) 2 gas sensor shows significant promise for real-time and stable monitoring of H 2 S gas in oxygen-deficient environments.

Background: The present video article describes the revision of a bone-anchored prosthesis in patients who received an osseointegration implant after transfemoral amputation. Clinical follow-up studies have shown that approximately 5% of all patients who receive press-fit cobalt-chromium alloy femoral implants experience failure of the intramedullary stem component as a result of septic loosening or stem breakage. For stem breakage, stem diameter and the occurrence of infectious events were identified as risk factors. We began regularly utilizing the standard German press-fit endo-exo cast cobalt-chrome implant in 2009, but changed to the forged titanium version in 2014 (BADAL X, OTN Implants) because of the breakages associated with the former implant. No breakages have been reported since making the switch, and as such we currently still utilize the titanium implant. Current Commission Européenne-certified bone-anchored implants for transfemoral amputation include a screw-type stem and a press-fit stem. The revision technique demonstrated in the present article may apply to both types of implant system, but this video is limited to demonstrating the use of a press-fit implant. We describe the 3 stages of debridement, removal, and subsequent implantation of a bone-anchored prosthesis in a revision setting., Description: We perform this procedure in up to 3 stages, with 10 to 12 weeks between removal of the failed implant and implantation of the revision prosthesis. For stage 1, in case of mechanical failure, the broken remnants of the implant, which may dangle in the soft tissues, are removed. The stoma is debrided, after which spontaneous stoma healing is achieved. In cases of septic loosening, stage 1 includes removal of the implant by retrograde hammering, followed by multiple debridements with flexible reamers and jet lavage until negative cultures are obtained. In stage 2, the broken osseointegration implant is removed with use of a custom-made titanium water-cooled hollow drill. With the use of this drill, we have always been successful in removing the broken implant while maintaining sufficient bone stock for future implant revision. If the corer fails, a larger approach is needed to remove the implant. The corer drill should have a wall that is as thin but as robust as possible in order to avoid cortical perforation, and should be manufactured from a strong material in order to resist the usage against the implant. We utilized a steel corer when initially performing this procedure, which was frequently unsuccessful, necessitating a larger approach to remove the implant. We currently utilize a 3D-printed corer drill with integrated water-cooling system with greater success (Xilloc Medical). This corer is custom-made and needs about 6 weeks for designing and manufacturing. This tool is utilized in the present video article. Stage 3 includes revision implantation of an osseointegration prosthesis, utilizing similar templating as in the primary surgical procedure. The time needed for the bone to recover from explantation is arbitrary, but we allow around 2 to 3 months before implanting a new intramedullary component. In cases of poor bone stock, a bone impaction graft can be applied prior to insertion of revision implant., Alternatives: A return to the prior mobilization level is an alternative to revision of the failed implant., Rationale: Failure due to stem breakage can occur in cases utilizing small-diameter cobalt-chromium implants. Such cases can be revised with use of large-diameter titanium implants, provided there is sufficient bone stock. Failure due to septic loosening may occur in patients who are not properly indicated for this procedure, such as those with severe dysvascular disease or diabetes mellitus. A revised implant is also at increased risk for recurrent failure., Expected Outcomes: Revision of bone-anchored prostheses includes up to 3 stages depending on whether the revision is for septic loosening or stem breakage. Although we allow 10 to 12 weeks before implanting a new intramedullary component, the time needed for the bone to recover from the explantation is arbitrary. During this interval, a temporary socket can be manufactured to allow mobilization with use of an artificial limb; however, most patients use just crutches and/or a wheelchair during this interval., Important Tips: Be aware of the type of implant that needs to be removed.Prepare for long operative times, especially in cases in which implants need to be cut or when dense cortical bone is expected.Account for 1.5 to 2 mm of extra diameter of the coring drill on either side in order to allow for the curvature of the press-fit implant.Plan for and acquire the right tools. Make sure to have at least 2 corer drills present in case of damage or malfunction.Utilize a fluoroscope frequently during initial drilling around the stem remnant.In case of poor bone stock, prepare for future bone impaction grafting when planning for revision implantation of a bone-anchored prosthesis., Acronyms and Abbreviations: OI = osseointegration implantBAP = bone-anchored prosthesisBIG = bone impaction grafting., Competing Interests: Disclosure: The Disclosure of Potential Conflicts of Interest forms are provided with the online version of the article (http://links.lww.com/JBJSEST/A468)., (Copyright © 2024 by The Journal of Bone and Joint Surgery, Incorporated.)

Background and Purpose: This study was undertaken to compare the performance of plasma p-tau181 with that of [ 18 F]fluorodeoxyglucose (FDG) positron emission tomography (PET) in the identification of early biological Alzheimer disease (AD)., Methods: We included 533 cognitively impaired participants from the Alzheimer's Disease Neuroimaging Initiative. Participants underwent PET scans, biofluid collection, and cognitive tests. Receiver operating characteristic analyses were used to determine the diagnostic accuracy of plasma p-tau181 and [ 18 F]FDG-PET using clinical diagnosis and core AD biomarkers ([ 18 F]florbetapir-PET and cerebrospinal fluid [CSF] p-tau181) as reference standards. Differences in the diagnostic accuracy between plasma p-tau181 and [ 18 F]FDG-PET were determined by bootstrap-based tests. Correlations of [ 18 F]FDG-PET and plasma p-tau181 with CSF p-tau181, amyloid β (Aβ) PET, and cognitive performance were evaluated to compare associations between measurements., Results: We observed that both plasma p-tau181 and [ 18 F]FDG-PET identified individuals with positive AD biomarkers in CSF or on Aβ-PET. In the MCI group, plasma p-tau181 outperformed [ 18 F]FDG-PET in identifying AD measured by CSF (p = 0.0007) and by Aβ-PET (p = 0.001). We also observed that both plasma p-tau181 and [ 18 F]FDG-PET metabolism were associated with core AD biomarkers. However, [ 18 F]FDG-PET uptake was more closely associated with cognitive outcomes (Montreal Cognitive Assessment, Mini-Mental State Examination, Clinical Dementia Rating Sum of Boxes, and logical memory delayed recall, p < 0.001) than plasma p-tau181., Conclusions: Overall, although both plasma p-tau181 and [ 18 F]FDG-PET were associated with core AD biomarkers, plasma p-tau181 outperformed [ 18 F]FDG-PET in identifying individuals with early AD pathophysiology. Taken together, our study suggests that plasma p-tau181 may aid in detecting individuals with underlying early AD., (© 2024 The Authors. European Journal of Neurology published by John Wiley & Sons Ltd on behalf of European Academy of Neurology.)

Background : Recent surgical innovations have increased treatment options for patients with facial nerve disorders (FNDs), leading to substantial improvements in functional and psychosocial outcomes. However, it is unclear whether sociodemographic factors are associated with the likelihood of undergoing dynamic facial reanimation procedures. Objective : In patients undergoing FND surgical treatment, what sociodemographic variables are associated with undergoing dynamic facial reanimation compared with static facial reanimation within a 16-year period? Methods : This was a retrospective study of adults undergoing surgical management for FND from 2007 to 2022 using the Merative ™ Marketscan ® Research Databases. Chi-squared and logistic regression analyses were performed. Results : Among 4,730 adults who underwent FND surgical intervention, 1,390 (34.2%) underwent dynamic facial reanimation. In multivariable regression analyses, more recent treatment year, younger age, and living in the Northeast United States were significant predictors of undergoing dynamic reanimation. Secondary analysis demonstrated that FND patients who were younger, female, and living in the Northeast United States were more likely to undergo concurrent selective neurectomy. Conclusions : These analyses demonstrate significant sociodemographic and temporal associations in the surgical management of FND. Future work is needed to evaluate how sociodemographic factors might influence access and decisions to pursue different types of reanimation procedures.

Neurostimulation delivers electrical pulses to modulate neuromuscular activity. Commonly used in medical interventions from pain relief to rehabilitation, neurostimulation typically uses manually placed hydrogel electrodes over the treated region. However, this method limits interventions requiring frequent, long-term daily use. To address this, novel fully textile electrodes are developed using industrial programmable knitting machines. These electrodes are designed to be washable, reusable, flexible, and breathable, with embedded interconnects. Textile electrodes are made of yarns with stainless steel and PEDOT-coated stainless steel conductive components. The electrodes' performance are compared with gel electrodes, characterizing impedance, sensorimotor stimulation thresholds, recruitment of induced movements, sensation levels, and perceived sensations. The effects of residential wash cycles and continuous use duration are also investigated. The proposed electrodes are found to perform similarly to hydrogel electrodes in all characterized metrics. No degradation in electrode performance is found after at least 30 wash cycles. Electrodes remained functionally intact after 1000 cycles of stretch loading at 50% of break strain. The textile electrodes consistently induced comfortable sensorimotor responses for at least six hours after donning. The proposed textile electrodes offer a novel and effective solution for neurostimulation interventions, paving the way for integration into smart garments and long-term wearable health technologies., (© 2024 Wiley‐VCH GmbH.)

Adult-onset asthma, notably prevalent among healthcare professionals, especially nurses, is often attributed to occupational factors such as exposure to cleaning agents. Studies consistently underscore the substantial role of such exposure in work-related asthma among hospital staff. We aimed to (a) identify and characterize current practices in cleaning and aerosolized medication administration; (b) assess changes in practices since a similar 2003 study of Texas healthcare workers; and (c) identify factors contributing to diverse exposures within healthcare job categories. We conducted focus groups with 38 participants in 6 healthcare settings, analyzing current practices, changes since 2003, and factors contributing to exposure diversity. We used a three-step approach for data analysis, including sociodemographic characterization, a scissor-and-sort technique for exposure description, and qualitative content analysis. Participants were primarily healthcare providers (76%) and housekeepers/cleaners (11%) who reported exposure to aerosolized medications, cleaning products, adhesives, and solvents. Participants reported transitioning from cleaning practices to new formulas with reduced odors and shifting from spray cleansers to wipes. Personal protective equipment (PPE) used during cleaning tasks varied, with training differing among job categories. Aerosolized medication administration varied among facilities, with reported medication types and protocol changes over time. The results emphasized the significance of maintaining uniform protection, disseminating knowledge, and consistently adhering to PPE protocols in the healthcare environment. Addressing the identified gaps in comprehension and potential sources of exposure variability requires additional focus on occupational health and safety initiatives., Competing Interests: Conflict of InterestThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Distal anterior cerebral artery (ACA) aneurysms comprise 4-5% of all intracranial aneurysms. 1-3 Rarely, these aneurysms can be complex and less amenable to conventional clipping or endovascular techniques, requiring alternative treatment strategies. 4,5 Surgical modalities employed in these situations may involve trapping and flow replacement techniques to exclude the aneurysm while maintaining normal perfusion to the affected territories. 4-7 In this video, we describe the Modified Trapping Technique for cases where two branches arise from the aneurysm and cannot be sacrificed. This technique involves the transposition of one of the branches and its reimplantation distally to the lesion. The aneurysm is then clipped, trapping the segment from which the disconnected branch originated, while preserving anterograde blood flow to both non-occluded and reimplanted branches. Compared to complete trapping in similar situations, this technique prevents the formation of a dead-end in the parent artery that could lead to thrombosis,8 poses no risk to uninvolved arteries and requires only one anastomosis. This technique was applied in a 54-year-old female patient who presented at our institution with an incidental fusiform distal ACA aneurysm diagnosed after head trauma. Imaging demonstrated that the aneurysm originated from a bihemispheric ACA with two pericallosal arteries arising from it. The patient tolerated the procedure well, and postoperative imaging showed complete aneurysm occlusion and patency of both the non-occluded and reimplanted pericallosal arteries. The patient consented to the procedure and the publication of her images. Institutional review board approval was deemed unnecessary., (Copyright © 2024. Published by Elsevier Inc.)

Background: Podoconiosis is a stigmatising neglected tropical condition, but the nature of podoconiosis stigma has not been fully explored. There is a growing understanding that the experience of stigma is intersectional, yet no research has been done on this matter in relation to podoconiosis. The aim of this paper is to contribute to the understanding of podoconiosis-related stigma by illustrating how multiple individuals' positionalities intersect to shape the experience of stigma due to podoconiosis., Methods: We used qualitative research to explore the experience of stigma among people affected by podoconiosis. Data were gathered using participant observation, interviews, focus group discussions and participatory methods. A total of 59 participants, including patients, local leaders, community health workers, and family members, were purposively selected to participate in this study., Findings: We identified three features in which stigma related to podoconiosis was grounded. These were bodily deformation, illness contamination and bodily weakness. The experience of stigma was shaped by the convergence of multiple individual positionalities and identities. Social positionalities and identities based on socio-economic, gender, age and illness status intersected to shape podoconiosis stigma., Conclusion: Our study demonstrates that the experience of stigma due to podoconiosis is intersectional, going beyond biological features of podoconiosis. The stigma experienced by affected individuals is complex, and shaped by the convergence of social structures and many individual identities such as socio-economic status, gender, disability and age. This understanding is crucial to analysing stigma related to podoconiosis, or other NTDs, and for designing interventions that address stigma that arise from biological aspects of disease and social factors simultaneously. Such holistic interventions can significantly improve the well-being of those affected by podoconiosis., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Bikorimana et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Ghanaians with perinatally acquired human immunodeficiency virus (HIV) infection now live into adulthood. It is known that adolescents and young adults living with HIV have a high risk of mental health comorbidity. Despite increasing global attention on HIV-mental health interactions, the field remains understudied in Ghana, with an attendant lack of national integrated care solutions. This study aimed to measure the burden and explore the context of depression, anxiety and stress symptoms among young people living with HIV receiving care at a tertiary care hospital in Ghana. This was an explanatory sequential mixed-methods study. Depression, anxiety and stress symptoms were measured using the Depression, Anxiety and Stress Scale, and their associations with quality of life (QoL), socioeconomic status, internalised stigma, disease stage and HIV-related risk-taking behaviours were explored. After preliminary quantitative data analysis, semi-structured interviews were conducted for those who screened positive for depression and/or anxiety to explore their experience with this comorbidity. This study found a low prevalence of depression and anxiety symptoms, which were associated with higher stigma scores and lower QoL. We believe this low prevalence to be attributable to the effect of several psychosocial interventional programmes, which were previously piloted with the study cohort that have gradually normalised mental health discussions. Participants also showed marked resilience and knowledge about their condition. The results of this study present an opportunity to advocate and scale up effective locally adapted and strength-based solutions to address the mental illness-HIV syndemic in Ghanaian young people living with HIV.

Introduction: Salivary carcinomas of the tongue represent a therapeutic challenge as their radical excision is particularly mutilating. We aimed to study the oncologic and functional outcomes of advanced stages salivary carcinomas of the tongue., Materials and Methods: This retrospective multicentric study, based on the French national network on rare head and neck cancers (REFCOR), included all patients with a T3-T4 salivary carcinoma of the tongue, diagnosed between January 2009 and December 2018., Results: In total, 47 patients were included, of which 44.7 % underwent surgery. Histologies were mostly adenoid cystic carcinomas (61.7 %), followed by other adenocarcinomas (27.7 %) and mucoepidermoid carcinomas (10.6 %). Median follow-up duration was 63.9 months. In multivariable analysis, surgery was significantly associated with better Recurrence-Free Survival (HR = 0.23, 95 %CI [0.09;0.55]) and Local/Regional Recurrence-Free Survival (HR = 0.31, 95 %CI [0.10;0.95]). The rate of distant metastasis at the end of follow-up was 61.9 % in the surgical group and 57.7 % in the non-surgical group. The Distant Metastasis Free Survival was 54.9 % [38.3;68.7], without statistical difference between both groups. There were similar rates of definitive gastrostomies but the rate of normal oral diet at the last follow-up seemed higher in the surgery group (38.1 % vs 15.4 %)., Conclusion: Radical surgery in that population mainly aims to improve local/regional control, which may result in better long-term swallowing functions. About half of these tumors may be associated with occult distant metastasis at initial presentation. More studies are warranted to establish the role of postoperative RT and non-surgical treatment with concurrent CRT., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Relapse after immunosuppression (IS) treatment withdrawal is frequent in patients with Autoimmune Hepatitis (AIH), and non-invasive biomarkers predictive of this risk are lacking. We assessed the frequency of circulating T cell subsets as potential biomarkers of disease activity and predictor of the risk of relapse after IS withdrawal. Serum levels of the cytokine B-cell Activating Factor (BAFF) were also investigated. Blood samples from 58 patients with active AIH, 56 AIH patients in remission, and 31 patients with NASH were analyzed. The frequency of activated CD4+ T peripheral helper (TPH) cells (CD4+CD45RA-CXCR5-PD1+CD38+) and of activated CD8+ T cells (CD8+CD45RA-PD1+CD38+) were assessed by flow cytometry. BAFF levels were determined by ELISA. Activated TPH and CD8+ T cell frequencies were significantly increased in patients with active AIH compared to remission AIH or NASH (TPH: 0.88% of total CD3+ vs. 0.42% and 0.39% respectively, p < 0.0001; CD8+ subset: 1.42% vs. 0.09% and 0.11% p < 0.0001). Among patients in remission undergoing treatment withdrawal (n = 18), those with increased frequencies of activated TPH (> 0.5% of total CD3+) and/or activated CD8+ T cells (> 0.18% total CD3+) had a higher risk of relapse (80% vs. 15% after 2 years, p = 0.0071). High BAFF serum concentration (> 213pg/ml) was also associated to a higher risk of relapse (57% vs. 11%, p = 0.0452). In conclusion, high frequency of activated TPH and of activated CD8+, as well as high levels of BAFF, before IS discontinuation, were significantly associated to a greater risk of relapse during the first two years. Thus, they represent promising biomarkers to provide personalized clinical follow-up for patients with AIH., (© 2024. The Author(s).)

Background: Colorectal cancer is a public health issue and was the third leading cause of cancer-related death worldwide in 2022. Early diagnosis can improve prognosis, making screening a central part of colorectal cancer management. Blood-based screening, diagnosis and follow-up of colorectal cancer patients are possible with the study of cell-free circulating tumor DNA. This study aimed to identify novel DNA methylation biomarkers of colorectal cancer that can be used for the follow-up of patients with colorectal cancer., Methods: A DNA methylation profile was established in the Gene Expression Omnibus (GEO) database (n = 507) using bioinformatics analysis and subsequently confirmed using The Cancer Genome Atlas (TCGA) database (n = 348). The in silico profile was then validated on local tissue and cell-free DNA samples using methylation-specific digital PCR in colorectal cancer patients (n = 35) and healthy donors (n = 35)., Results: The DNA methylation of COL25A1 and METAP1D was predicted to be a colorectal cancer biomarker by bioinformatics analysis (ROC AUC = 1, 95% CI [0.999-1]). The two biomarkers were confirmed with tissue samples, and the combination of COL25A1 and METAP1D yielded 49% sensitivity and 100% specificity for cell-free DNA., Conclusion: Bioinformatics analysis of public databases revealed COL25A1 and METAP1D DNA methylation as clinically applicable liquid biopsies DNA methylation biomarkers. The specificity implies an excellent positive predictive value for follow-up, and the high sensitivity and relative noninvasiveness of a blood-based test make these biomarkers compatible with colorectal cancer screening. However, the clinical impact of these biomarkers in colorectal cancer screening and follow-up needs to be established in further prospective studies., (© 2024. The Author(s).)

Competing Interests: Disclosure of interest: The authors completed the ICMJE Disclosure of Interest Form (available upon request from the corresponding author) and disclose no relevant interests.

DNA double-strand breaks (DSBs) must be properly repaired within diverse chromatin domains to maintain genome stability. Whereas euchromatin has an open structure and is associated with transcription, facultative heterochromatin is essential to silence developmental genes and forms compact nuclear condensates, called polycomb bodies. Whether the specific chromatin properties of facultative heterochromatin require distinct DSB repair mechanisms remains unknown. Here, we integrate single DSB systems in euchromatin and facultative heterochromatin in Drosophila melanogaster and find that heterochromatic DSBs rapidly move outside polycomb bodies. These DSB movements coincide with a break-proximal reduction in the canonical heterochromatin mark histone H3 Lysine 27 trimethylation (H3K27me3). We demonstrate that DSB movement and loss of H3K27me3 at heterochromatic DSBs depend on the histone demethylase dUtx. Moreover, loss of dUtx specifically disrupts completion of homologous recombination at heterochromatic DSBs. We conclude that DSBs in facultative heterochromatin require dUtx-mediated loss of H3K27me3 to promote DSB movement and repair., (© 2024. The Author(s).)

The use of microextraction or sequestration offers a promising method for removing chemicals from polluted water. Simple coacervates, which are water-in-water droplets, present the advantage of being formed at a given pH while being destroyed upon pH-change. Theoretically, such stimuli-responsiveness could be leveraged to recover the pollutant. Coacervates have shown exceptional capability in sequestering diverse chemicals and colloids. In this paper, we seek to understand more in-depth the sequestration mechanisms occurring with a variety of usual ionic pollutants, both qualitatively and quantitatively, since the presence of ions can affect the coacervate formation. By combining microscopy observations with spectroscopic analysis, we have precisely defined the nature and strength of the interactions between coacervates and chemicals. Our findings indicate that polluted solutions treated with coacervates show removal efficiencies ranging from 30% to 90%. We highlight that factors such as charge, concentration, solubility, and process play critical roles in the sequestration efficiency of these coacervates. Understanding these interactions is crucial for advancing several fields, particularly in water purification processes.

Circulating vaccine-derived polioviruses (cVDPVs) can emerge and lead to outbreaks of paralytic polio as well as asymptomatic transmission in communities with a high percentage of undervaccinated children. Using data from the World Health Organization Polio Information System and Global Polio Laboratory Network, this report describes global polio outbreaks due to cVDPVs during January 2023-June 2024 and updates previous reports. During the reporting period, 74 cVDPV outbreaks were detected in 39 countries or areas (countries), predominantly in Africa. Among these 74 cVDPV outbreaks, 47 (64%) were new outbreaks, detected in 30 (77%) of the 39 countries. Three countries reported cVDPV type 1 (cVDPV1) outbreaks and 38 countries reported cVDPV type 2 (cVDPV2) outbreaks; two of these countries reported cocirculating cVDPV1 and cVDPV2. In the 38 countries with cVDPV2 transmission, 70 distinct outbreaks were reported. In 15 countries, cVDPV transmission has lasted >1 year into 2024. In Nigeria and Somalia, both countries with security-compromised areas, persistent cVDPV2 transmission has spread to neighboring countries. Delayed implementation of outbreak response campaigns and low-quality campaigns have resulted in further international spread. Countries can control cVDPV outbreaks with timely allocation of resources to implement prompt, high-quality responses after outbreak confirmation. Stopping all cVDPV transmission requires effectively increasing population immunity by overcoming barriers to reaching children., Competing Interests: All authors have completed and submitted the International Committee of Medical Journal Editors form for disclosure of potential conflicts of interest. No potential conflicts of interest were disclosed.

Background: Vaptans were developed at the end of the previous century as V2R antagonists. Tolvaptan is the most prescribed vaptan for hyponatremia and the autosomal polycystic kidney disease (ADPKD). However, its use is not as widespread as it should be due to price issues, a narrow therapeutic window and some side effects. With the aim of discovering new efficient and safer V2R antagonists, we screened animal venoms and identified several interesting peptide toxins. Among them, MQ1 displayed such unique biological properties in that regard that it was the starting point for the development of a potential drug candidate., Methods: Human T-cell assays and bioinformatics was used to mitigate MQ1 immunogenicity risk. The MQ232 biodistribution in mice was done by positron emission tomography (PET). Pharmacodynamics, pharmacokinetics, acute and chronic toxicity tests were performed on control rats. A rat experimental model of dDAVP-induced hyponatremia, an ex vivo mice model of renal cysts and a mice orthologous model of ADPKD were used to validate MQ232 efficacy in these pathologies., Results: Three mutations were introduced in MQ1 to mitigate its immunogenicity risk. A fourth gain-of-function mutation was added to generate MQ232. MQ232's safety was demonstrated by a first toxic dose as high as 3,000 nmol/kg and a strong kidney organ selectivity by PET imaging, while showing almost no interaction with the liver. MQ232's efficacy was first demonstrated with an effective dose of 3 nmol/kg in a hyponatremic model, and then in polycystic kidney models on which MQ232 significantly reduced cyst growth., Conclusions: We demonstrated, employing diverse translational techniques and minimizing animal use, MQ232's safety and efficacy in several rodent models of hyponatremia and ADPKD., (Copyright © 2024 by the American Society of Nephrology.)