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BackgroundIncreasing HIV testing and treatment coverage among people living with HIV (PLHIV) is essential for achieving global HIV epidemic control. However, compared to women, cis-gender heterosexual men living with HIV are significantly less likely to know their HIV status, initiate anti-retroviral therapy (ART) and achieve viral suppression. This is particularly true in South Africa, where men are also at increased risk of mortality resulting from AIDS-related illnesses. While there is growing knowledge of Treatment as Prevention or the concept Undetectable = Untransmittable (U = U) among PLHIV in Western and high-income countries, the reach and penetration of the U = U message in sub-Saharan Africa remains limited, and few studies have evaluated the impact of accessible and relatable U = U messages on ART initiation and adherence. To address these gaps, rigorous evaluations of interventions that incorporate U = U messages are needed, especially among men in high prevalence settings.MethodsBuilding on our U = U messages that we previously developed for men using behavioral economics insights and a human-centered design, we will conduct two sequential hybrid type 1 effectiveness-implementation trials to evaluate the impact of U = U messages on men's uptake of community-based HIV testing and ART initiation (Trial 1), and retention in care and achievement of viral suppression (Trial 2). For trial 1, a cluster randomized trial will be implemented with HIV testing service site-days (each day at one testing site) randomized to U = U or standard-of-care (SoC) messages inviting men to test for HIV. For trial 2, an individual-level randomized control trial will be implemented, with men initiating ART at six government clinics randomized to receive U = U counselling or SoC treatment adherence messaging. We will incorporate a multi-method evaluation to inform future implementation of U = U messaging interventions. The study will be conducted in the Buffalo City Metro Health District of the Eastern Cape Province and in the Cape Town Metro Health District in the Western Cape Province in South Africa.DiscussionThese trials are the first to rigorously evaluate the impact of U = U messaging on HIV testing uptake, ART initiation and achievement of viral suppression among African men. If effective, these messaging interventions can shape global HIV testing, treatment and adherence counselling guidelines and practices.

Aims:: The working group (WG) initiated by the International Continence Society Standardization Steering Committee and supported by the Society of Urodynamics, Female Pelvic Medicine and Urogenital Reconstruction has revised the (1997) ICS Standard for pressure flow studies. Methods:: Based on the ICS standard for developing evidence-based standards, the WG developed this new ICS standard in the period from May 2020 to December 2022. A draft was posted on the ICS website in January 2023 to facilitate public discussion and the comments received have been incorporated into this final release. Results:: The WG summarizes the theory and recommends the practice and the terms used for the diagnosis of voiding dysfunction for adult female and male patients without relevant neurological abnormalities, in part 1 of this standard. The WG has also recommended standard principles and parameters for objective and continuous grading of urethral resistance and detrusor voiding contraction on the basis of pressure flow studies in part 2. The recommendations for practice in this part have also the aim to increase the understanding of the physiology as well as the psychology of voiding. The potential effects of the laboratory situation of the test on the voiding as well as the role of the urodynamicist in this regard are discussed. The WG has recommended to use for diagnosis only the voidings that are considered representative by the patient. Conclusion:: A pressure flow study is the gold standard to assess voiding function and to quantify dysfunction. This part of the standard explains the clinical background, gives recommendations for the execution of a pressure flow study and lists relevant terms, parameters, and units of measurements.

Aims:: The Working Group (WG), initiated by the International Continence Society (ICS) Standardisation Steering Committee and supported by the Society of Urodynamics, Female Pelvic Medicine and Urogenital Reconstruction, has revised the ICS Standard for pressure-flow studies of 1997. Methods:: Based on the ICS standard for developing evidence-based standards, the WG developed this new ICS standard in the period from May 2020 to December 2022. A draft was posted on the ICS website in December 2022 to facilitate public discussion and the comments received have been incorporated into this final release. Results:: The WG has recommended analysis principles for the diagnosis of voiding dysfunction for adult men and women without relevant neurological abnormalities. New standard terms and parameters for objective and continuous grading of urethral resistance (UR), bladder outflow obstruction (BOO) and detrusor voiding contraction (DVC) are introduced in this part 2 of the standard. The WG has summarized the theory and recommendations for the practice of pressure-flow study (PFS) for patients in part 1. A pressure-flow plot is recommended for the diagnosis of every patient, in addition to time-based graphs. Voided percentage and post void residual volume should always be included in PFS analysis and diagnosis. Only parameters that represent the ratio or subtraction of pressure and synchronous flow are recommended to quantify UR and only parameters that combine pressure and flow in a product or sum are recommended to quantify DVC. The ICS BOO index and the ICS detrusor contraction index are introduced in this part 2 as the standard. The WG has suggested clinical PFS dysfunction classes for male and female patients. A pressure-flow scatter graph including every patient’s pdet at maximum flow (pdetQmax) with maximum flow rate (Qmax) point should be included in all scientific reports considering voiding dysfunction. Conclusion:: PFS is the gold standard used to objectively assess voiding function. Quantifying the dysfunction and grading of abnormalities are standardized for adult males and females.

E-cycling is a growing area of cycling appealing to competitive cyclists and fitness enthusiasts. Zwift is the most popular e-cycling platform, with approx. 1 million subscribers and is a virtual environment that hosts regular races, including the UCI e-cycling world championships. The popularity of Zwift has given rise to cases of cheating and hacking the system to gain an advantage in e-racing. As a result, some high-profile professional riders have faced bans. We set out to understand the thoughts and concerns e-cyclists have about cheating, hacking, and doping in e-cycling. A total of 337 females and 1130 males were recruited over a 7-week period via social networking sites to complete an online survey. Forty-four per cent had experienced cheating during e-racing, which made them feel angry, annoyed, disappointed, and cheated. However, 15% of those who experienced cheating said they did not care, possibly because many see e-racing as a game or training tool rather than a competitive event. Eighty-seven per cent of participants were in favour of enforcing a ban on cheaters in e-cycling, while 34% wanted cheaters to be banned during in-person cycling events too. Results indicate that many e-cyclists have experienced cheating and would like clearer rules and bans for cheaters during e-races.

Consumption of broccoli mediates numerous chemo-protective benefits through the intake of phytochemicals, some of which modulate aryl hydrocarbon receptor (AHR) activity. Whether AHR activation is a critical aspect of the therapeutic potential of dietary broccoli is not known. Here we administered isocaloric diets, with or without supplementation of whole broccoli (15% w/w), to congenic mice expressing the high-affinity Ahrb/b or low-affinity Ahrd/d alleles, for 24 days and examined the effects on AHR activity, intestinal microbial community structure, inflammatory status, and response to chemically induced colitis. Cecal microbial community structure and metabolic potential were segregated according to host dietary and AHR status. Dietary broccoli associated with heightened intestinal AHR activity, decreased microbial abundance of the family Erysipelotrichaceae, and attenuation of colitis. In summary, broccoli consumption elicited an enhanced response in ligand-sensitive Ahrb/b mice, demonstrating that in part the beneficial aspects of dietary broccoli upon intestinal health are associated with heightened AHR activity.

Objective This study aimed to explore the potential for the Waterlow score (WS) to be used as a predictor of 30-day mortality and length of hospital stay (LHS) in acutely admitted medical patients aged 65 years and older.Design Prospective observational cohort study.Setting UK District General Hospital.Subjects 834 consecutive patients aged 65 years and older admitted acutely to medical specialties between 30 May and 22 July 2014.Methods Admission WS (range 4–64) assessment paired with the patient’s status at 30 days in terms of mortality and their LHS.Primary outcomes 30-day mortality and length of inpatient stay.Results 834 consecutive acute medical admissions had their WS recorded. 30-day mortality was 13.1% (109 deaths). A significant difference in the distribution of WS (p

Transaminases are pyridoxal-5′-phosphate (PLP) binding enzymes, broadly studied for their potential industrial application. Their affinity for PLP has been related to their performance and operational stability and while significant differences in PLP requirements have been reported, the environment of the PLP-binding pocket is highly conserved. In this study, thorough analysis of the residue interaction network of three homologous transaminases Halomonas elongata (HeTA), Chromobacterium violaceum (CvTA), and Pseudomonas fluorescens (PfTA) revealed a single residue difference in their PLP binding pocket: an asparagine at position 120 in HeTA. N120 is suitably positioned to interact with an aspartic acid known to protonate the PLP pyridinium nitrogen, while the equivalent position is occupied by a valine in the other two enzymes. Three different mutants were constructed (HeTA-N120V, CvTA-V124N, and PfTA-V129N) and functionally analyzed. Notably, in HeTA and CvTA, the asparagine variants, consistently exhibited a higher thermal stability and a significant decrease in the dissociation constant (Kd) for PLP, confirming the important role of N120 in PLP binding. Moreover, the reaction intermediate pyridoxamine-5′-phosphate (PMP) was released more slowly into the bulk, indicating that the mutation also enhances their PMP binding capacity. The crystal structure of PfTA, elucidated in this work, revealed a tetrameric arrangement with the PLP binding sites near the subunit interface. In this case, the V129N mutation had a negligible effect on PLP-binding, but it reduced its temperature stability possibly destabilizing the quaternary structure.

Introduction Primary healthcare records are used for studies within large data repositories. One of the limitations of using these routinely collected data for epilepsy research is the possibility of including incorrectly recorded diagnoses. To our knowledge, the accuracy of UK GP diagnosis codes for epilepsy has only partially been validated. Objectives and Approach We aimed to validate the accuracy of case ascertainment algorithms in identifying people with epilepsy in routinely collected Welsh healthcare data. A reference population of 150 people with definite epilepsy and 150 people without epilepsy was ascertained from hospital records and linked to records held within the Secure Anonymised Information Linkage (SAIL) databank in Wales. We used three different algorithms to identify the reference population: a) individuals with an epilepsy diagnosis code and two consecutive AED prescription codes; b) individuals with an epilepsy diagnosis code only; c) individuals with two consecutive AED prescription codes only. Results We applied the algorithms to all patients and to adults and children separately. For all patients, combining diagnosis and AED prescription codes had a sensitivity of 84% (95% ci 77–90) and specificity of 98% (95–100) in identifying people with epilepsy; diagnosis codes alone had a sensitivity of 86% (80–91) and a specificity of 97% (92–99); and AED prescription codes alone achieved a sensitivity of 92% (70–83) and a specificity of 73% (65–80). Using AED codes only was more accurate in children, achieving a sensitivity of 88% (75–95) and specificity of 98% (88–100). This can be explained by the widespread use of AEDs for indications other than epilepsy in adults, which is not the case for children. Conclusion/Implications GP epilepsy diagnosis and AED prescription codes can be used to identify people with epilepsy using anonymised healthcare records in Wales. In children using AED prescription codes alone is an accurate way to identify epilepsy cases. These results are generalizable to other studies that use UK primary care records.

This study aimed to address two queries: firstly, the relationship between two cataract surgical feedback tools for training, one human and one software based, and, secondly, evaluating microscope control during phacoemulsification using the software. Videos of surgeons with varying experience were enrolled and independently scored with the validated PhacoTrack motion capture software and the Objective Structured Assessment of Cataract Surgical Skill (OSACCS) human scoring tool. Microscope centration and path length travelled were also evaluated with the PhacoTrack software. Twenty-two videos correlated PhacoTrack motion capture with OSACCS. The PhacoTrack path length, number of movements, and total procedure time were found to have high levels of Spearman’s rank correlation of -0.6792619 (p=0.001), -0.6652021 (p=0.002), and -0.771529 (p=0001), respectively, with OSACCS. Sixty-two videos evaluated microscope camera control. Novice surgeons had their camera off the pupil centre at a far greater mean distance (SD) of 6.9 (3.3) mm, compared with experts of 3.6 (1.6) mm (p≪0.05). The expert surgeons maintained good microscope camera control and limited total pupil path length travelled 2512 (1031) mm compared with novices of 4049 (2709) mm (p≪0.05). Good agreement between human and machine quantified measurements of surgical skill exists. Our results demonstrate that surrogate markers for camera control are predictors of surgical skills.