MST1 Negatively Regulates TNFα-Induced NF-κB Signaling through Modulating LUBAC Activity.

The nuclear factor (NF)-κB pathway plays a central role in inflammatory and immune responses, with aberrant activation of NF-κB signaling being implicated in various human disorders. Here, we show that mammalian ste20-like kinase 1 (MST1) is a previously unrecognized component of the tumor necrosis factor α (TNFα) receptor 1 signaling complex (TNF-RSC) and attenuates TNFα-induced NF-κB signaling. Genetic ablation of MST1 in mouse embryonic fibroblasts and bone marrow-derived macrophages potentiated the TNFα-induced increase in IκB kinase (IKK) activity, as well as the expression of NF-κB target genes. TNFα induced the recruitment of MST1 to TNF-RSC and its interaction with HOIP, the catalytic component of the E3 ligase linear ubiquitin assembly complex (LUBAC). Furthermore, MST1 activated in response to TNFα stimulation mediates the phosphorylation of HOIP and thereby inhibited LUBAC-dependent linear ubiquitination of NEMO/IKKγ. Together, our findings suggest that MST1 negatively regulates TNFα-induced NF-κB signaling by targeting LUBAC.

Elemental Diet as a Therapeutic Modality: A Comprehensive Review.

Elemental diets have been employed for the management of various diseases for over 50 years, with several mechanisms mediating their beneficial effects. Yet, they are underutilized due to poor palatability, access, cost, and lack of awareness regarding their clinical efficacy. Therefore, in this review, we aimed to systematically search and review the literature to summarize the formulation variability, mechanisms of action, clinical applications, and tolerability of the elemental diets in gastrointestinal diseases. While large prospective trials are lacking, elemental diets appear to exhibit objective and subjective clinical benefit in several diseases, including eosinophilic esophagitis, eosinophilic gastroenteritis, inflammatory bowel diseases, small intestinal bacterial overgrowth, intestinal methanogen overgrowth, chemoradiotherapy-associated mucositis, and celiac disease. Although some data support the long-term use of elemental diets as an add-on supplement for chronic pancreatitis and Crohn's disease, most of the literature on exclusive elemental diets focuses on inducing remission. Therefore, subsequent treatment strategies for maintaining remission need to be adopted in chronic/relapsing diseases. Several mechanistic pathways were identified to mediate the effects of elemental diets, including food additive and allergen-free content, high passive absorption rate, and anti-inflammatory properties. High rates of intolerance up to 40% are seen in the trials where exclusive elemental diets were administered orally due to poor organoleptic acceptability; however, when tolerated, adverse events were rare. Other limitations of elemental diets are cost, access, and lifestyle/social restrictions. Moreover, judicious use is advised in presence of a concomitant restrictive food intake disorders. Elemental diets offer a potentially highly efficacious dietary intervention with minor side effects. Palatability, cost, access, and social restrictions are common barriers of use. Prospective clinical trials are needed to elucidate the role of elemental formulas in the management of individual diseases.

The role of peer support in recovery among clients with mental illness attending the psychiatric service in a tertiary hospital in Malaysia: a qualitative study.

BACKGROUND: The understanding that mental health recovery is a personal and subjective experience informs mental health policies in many countries. However, most of the populations in these studies are from the West, limiting their applicability in Asia. Peer support in mental health refers to helping and mentoring people who have overcome similar obstacles. Despite being proven to be effective in promoting recovery, little is known about its use in Malaysian psychiatric patients. This study aims to explore the participants' perspectives on their concept of recovery and how the peer support group (PSG) aid them to achieve recovery. METHODOLOGY: This study was conducted on clients with mental illness who attended the PSG provided by the Community Psychiatry and Psychosocial Intervention Unit in National University Malaysia Medical Centre. A qualitative generic inductive approach was employed in this thematic exploratory study. Purposive sampling was the method used to collect the data for this thematic exploratory study. In-depth interviews of 11 study participants were audio recorded and transcribed verbatim. Data were analyzed using Braun and Clarke (2006) descriptive thematic analysis method. RESULTS: The findings of this study highlighted six key themes; three pertaining to the participants' perspectives on the meaning of recovery (1. Gaining self-reliance and social inclusion, 2. Personal growth and improved life circumstances in recovery, and 3. Symptoms improvement) and another three pertaining to how the peer support group aids recovery (1. Empowerment and growth through peer support, 2. Promoting well-being, 3. Social connection and support). CONCLUSION: The findings of this study provide valuable insights into the perspectives of psychiatry clinic patients enrolled in PSG on the concept of recovery and the role of such groups in their recovery journey. The findings demonstrated that the PSG complemented the participants' perspectives on recovery, reinforcing the notion that a comprehensive and person-centered approach to mental health services is essential for successful and sustained recovery outcomes.

Ultrasound biomicroscopy in the management of complex cataract and intraocular lens: A review.

Ultrasound biomicroscopy (UBM) is an invaluable investigation for imaging anterior segment structures. Although it is operator-dependent and time consuming, unlike optical-based imaging techniques, it is able to image structures posterior to the iris, such as the zonules, ciliary body and part of the pars plana. It is especially useful in advanced cataracts, traumatic cataracts, subluxed lenses, posterior polar cataracts, and congenital and developmental anomalies affecting the anterior segment. It provides diagnostic information in eyes with complex cataracts or intraocular lens (IOL)-related pathology, and aids in surgical planning in order to minimise complications. In this review, we describe the UBM features of various lenticular pathologies and demonstrate its application in the diagnosis and surgical management of lens and IOL-related pathologies.

The Use of E-Learning in Peyton's 4-Step Approach: Evaluation of Facial Computed Tomography Scans.

Imparting procedural skills is challenging. Peyton's approach is an effective face-to-face teaching technique increasingly used in complex skills training. Institutions are beginning to incorporate online training as part of their procedural curriculum. We developed E-Peyton's to employ Peyton's approach through an electronic learning platform. The efficacy of E-Peyton's approach in teaching the interpretation of facial computed tomography (CT) scans is evaluated in this study. Naïve learners (n=41) were randomized into 2 groups based on teaching techniques employed: E-Peyton's (n=20) and Peyton's (n=21) approaches. The distance between the infraorbital margin and the posterior ledge was measured using a 3-part standardized measuring protocol on OsiriX. Twenty measurements were assessed for accuracy against the benchmark (±2 mm) at week 0 and week 1. Training durations were compared. Questionnaires were administered before and after the study to identify learners' acceptance of teaching techniques and their confidence in interpreting facial CT scans. Learners in both teaching techniques had comparable skills retention. Gap scores indicate significant improvement in learner's confidence levels regardless of teaching technique (P<0.05). Both teaching techniques were well-accepted by learners. E-Peyton's and Peyton's approaches required a similar training duration. The COVID-19 pandemic highlights the importance of effective remote learning platforms. E-Peyton's approach is comparable to that of Peyton's in all areas of assessment. E-Peyton's approach effectively automates Peyton's approach, allowing for standardized, high-quality procedural skills training while reducing manpower burden.

Postoperative Scar Management Protocol for Asian Patients.

BACKGROUND: Postoperative scar formation remains a morbidity for patients even with the advent of minimally invasive techniques. Furthermore, the significant difference between the Asian and Caucasian skin results in poorer postoperative scar outcomes in Asians, supporting the need for an evidence-based scar management protocol. METHODS: Following a literature review of the PubMed and the Cochrane databases over the past 10 years, we constructed a novel postoperative scar management protocol for the Asian skin, utilized in a Singaporean tertiary healthcare institution. RESULTS: We describe a timeline-based scar protocol from the point of skin closure to a minimum of 1 year of follow-up. We support the use of intraoperative botulinum toxin for selected high-risk individuals upon skin closure with a follow-up regimen in the postoperative setting. For recalcitrant keloids, we have described a multimodal therapy comprising elements of intralesional steroids, botulinum toxin, lasers, surgery, and radiotherapy. CONCLUSIONS: A consolidated postoperative scar management protocol provides the necessary guidance for improved scar outcomes in the Asian skin. There is inherent potential in expanding the protocol to include post-traumatic and burn wounds or support other skin types including the Caucasian skin. NO LEVEL ASSIGNED: This journal requires that authors assign a level of evidence to each submission to which Evidence-Based Medicine rankings are applicable. This excludes Review Articles, Book Reviews, and manuscripts that concern Basic Science, Animal Studies, Cadaver Studies, and Experimental Studies. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

Irritable Bowel Syndrome-Like Symptoms in Quiescent Inflammatory Bowel Disease: A Practical Approach to Diagnosis and Treatment of Organic Causes.

BACKGROUND: Despite achieving remission in inflammatory bowel disease (IBD), persistent gastrointestinal symptoms are common in quiescent IBD. While irritable bowel syndrome (IBS) is commonly diagnosed in IBD, IBS-like symptoms of recurrent abdominal pain and altered bowel habits can also be attributed to a wide range of overlapping gastrointestinal (GI) etiologies and systemic disorders with GI manifestations that often do not respond to conventional IBS therapies. Delay in diagnosis of these conditions can lead to ongoing patient suffering, reduced quality of life, repetition of invasive testing, increased healthcare utilization, and potentially unnecessary empirical escalation of IBD-related treatments. AIMS: This review provides a practical approach for the evaluation and diagnosis of IBS mimickers in IBD. We summarize the definition, pathophysiology, diagnosis and treatment of the potential etiologies causing unexplained GI symptoms. CONCLUSION: Overlapping conditions can co-exist with IBD and explain IBS-like symptoms. The diagnostic work-up in this population should be individualized and tailored to the predominant symptom pattern, associated clinical signs and symptoms and predisposing conditions that can be obtained from a detailed history and physical examination.

Estimating direct and spill-over impacts of political elections on COVID-19 transmission using synthetic control methods.

Mass gathering events have been identified as high-risk environments for community transmission of coronavirus disease 2019 (COVID-19). Empirical estimates of their direct and spill-over effects however remain challenging to identify. In this study, we propose the use of a novel synthetic control framework to obtain causal estimates for direct and spill-over impacts of these events. The Sabah state elections in Malaysia were used as an example for our proposed methodology and we investigate the event's spatial and temporal impacts on COVID-19 transmission. Results indicate an estimated (i) 70.0% of COVID-19 case counts within Sabah post-state election were attributable to the election's direct effect; (ii) 64.4% of COVID-19 cases in the rest of Malaysia post-state election were attributable to the election's spill-over effects. Sensitivity analysis was further conducted by examining epidemiological pre-trends, surveillance efforts, varying synthetic control matching characteristics and spill-over specifications. We demonstrate that our estimates are not due to pre-existing epidemiological trends, surveillance efforts, and/or preventive policies. These estimates highlight the potential of mass gatherings in one region to spill-over into an outbreak of national scale. Relaxations of mass gathering restrictions must therefore be carefully considered, even in the context of low community transmission and enforcement of safe distancing guidelines.

Novel technical and privacy-preserving technology for artificial intelligence in ophthalmology.

PURPOSE OF REVIEW: The application of artificial intelligence (AI) in medicine and ophthalmology has experienced exponential breakthroughs in recent years in diagnosis, prognosis, and aiding clinical decision-making. The use of digital data has also heralded the need for privacy-preserving technology to protect patient confidentiality and to guard against threats such as adversarial attacks. Hence, this review aims to outline novel AI-based systems for ophthalmology use, privacy-preserving measures, potential challenges, and future directions of each. RECENT FINDINGS: Several key AI algorithms used to improve disease detection and outcomes include: Data-driven, imagedriven, natural language processing (NLP)-driven, genomics-driven, and multimodality algorithms. However, deep learning systems are susceptible to adversarial attacks, and use of data for training models is associated with privacy concerns. Several data protection methods address these concerns in the form of blockchain technology, federated learning, and generative adversarial networks. SUMMARY: AI-applications have vast potential to meet many eyecare needs, consequently reducing burden on scarce healthcare resources. A pertinent challenge would be to maintain data privacy and confidentiality while supporting AI endeavors, where data protection methods would need to rapidly evolve with AI technology needs. Ultimately, for AI to succeed in medicine and ophthalmology, a balance would need to be found between innovation and privacy.

MST1 mediates the N-methyl-D-aspartate-induced excitotoxicity in mouse cortical neurons.

Excessive activation of the ionotropic N-methyl-D-aspartate (NMDA) receptor has been shown to cause abnormally high levels of Ca2+ influx, thereby leading to excitotoxic neuronal death. In this study, exposure of mouse primary cortical neurons to NMDA resulted in the cleavage and activation of mammalian sterile 20-like kinase-1 (MST1), both of which were mediated by calpain 1. In vitro cleavage assay data indicated that calpain 1 cleaves out the autoinhibitory domain of MST1 to generate an active form of the kinase. Furthermore, calpain 1 mediated the cleavage and activation of wild-type MST1, but not of MST1 (G339A). Intriguingly, NMDA/calpain-induced MST1 activation promoted the nuclear translocation of the kinase and the phosphorylation of histone H2B in mouse cortical neurons, leading to excitotoxicity. Thus, we propose a previously unrecognized mechanism of MST1 activation associated with NMDA-induced excitotoxic neuronal death.

Residential urban food environment profiles and diet outcomes among adults in Brooklyn, New York: a cross-sectional study.

OBJECTIVE: To assess the clustering properties of residential urban food environment indicators across neighbourhoods and to determine if clustering profiles are associated with diet outcomes among adults in Brooklyn, New York. DESIGN: Cross-sectional. SETTING: Five neighbourhoods in Brooklyn, New York. PARTICIPANTS: Survey data (n 1493) were collected among adults in Brooklyn, New York between April 2019 and September 2019. Data for food environment indicators (fast-food restaurants, bodegas, supermarkets, farmer's markets, community kitchens, Supplemental Nutrition Assistance Program application centres, food pantries) were drawn from New York databases. Latent profile analysis (LPA) was used to identify individuals' food access-related profiles, based on food environments measured by the availability of each outlet within each participant's 800-m buffer. Profile memberships were associated with dietary outcomes using mixed linear regression. RESULTS: LPA identified four residential urban food environment profiles (with significant high clusters ranging from 17 to 57 across profiles): limited/low food access, (n 587), bodega-dense (n 140), food swamp (n 254) and high food access (n 512) profiles. Diet outcomes were not statistically different across identified profiles. Only participants in the limited/low food access profile were more likely to consume sugar-sweetened beverages (SSB) than those in the bodega-dense profile (b = 0·44, P < 0·05) in adjusted models. CONCLUSIONS: Individuals in limited and low food access neighbourhoods are vulnerable to consuming significant amounts of SSB compared with those in bodega-dense communities. Further research is warranted to elucidate strategies to improve fruit and vegetable consumption while reducing SSB intake within residential urban food environments.

COVID-19 and the shifting organisation of sex work markets in Singapore.

While past studies have sought to capture how the COVID-19 pandemic has impacted on the health and sexual lives of sex workers internationally, less attention has been paid to the reorganisation of sex markets as a result of COVID-19. We conducted a sequential exploratory mixed methods study using in-depth interviews, cyber ethnography and surveyor-administered structured surveys among sex workers. We report two key findings on how the pandemic has impacted sex markets in Singapore. First, the organisation of sex markets shifted as a result of lockdown and associated movement control measures. This shift was characterised by the out-migration of sex workers, the reduction in supply and demand for in-person sex work, and a shift towards online spaces. Second, we found that sex workers experienced greater economic hardship as a result of such changes. Given the potential shifts in sex markets as a result of the pandemic, we adopt a World Health Organisation Health Workplace Framework and Model to identify interventions to improve the occupational safety and health of sex workers in a post-COVID-19 era.

The Impact of the Coronavirus Disease (COVID-19) on the Health and Social Needs of Sex Workers in Singapore.

We evaluated the impact of the coronavirus disease (COVID-19) on the sex work industry and assessed how it has impacted the health and social conditions of sex workers in Singapore. We conducted a sequential exploratory mixed methods study amidst the COVID-19 pandemic from April to October 2020, including in-depth interviews with 24 stakeholders from the sex work industry and surveyor-administered structured surveys with 171 sex workers. COVID-19 had a substantial impact on sex workers' income. The illegality of sex work, stigma, and the lack of work documentation were cited as exclusionary factors for access to alternative jobs or government relief. Sex workers had experienced an increase in food insecurity (57.3%), housing insecurity (32.8%), and sexual compromise (8.2%), as well as a decrease in access to medical services (16.4%). Being transgender female was positively associated with increased food insecurity (aPR = 1.23, 95% CI [1.08, 1.41]), housing insecurity (aPR = 1.28, 95% CI [1.03, 1.60]), and decreased access to medical services (aPR = 1.74, 95% CI [1.23, 2.46]); being a venue-based sex worker was positively associated with increased food insecurity (aPR = 1.46, 95% CI [1.00, 2.13]), and being a non-Singaporean citizen or permanent resident was positively associated with increased housing insecurity (aPR = 2.59, 95% CI [1.73, 3.85]). Our findings suggest that COVID-19 has led to a loss of income for sex workers, greater food and housing insecurity, increased sexual compromise, and reduced access to medical services for sex workers. A lack of access to government relief among sex workers exacerbated such conditions. Efforts to address such population health inequities should be implemented.

Disinfection capabilities of a 222 nm wavelength ultraviolet lighting device: a pilot study.

OBJECTIVE: To demonstrate the efficacy of the SafeZone UVC (Ushio Inc., Japan) 222 nm ultraviolet C (UVC) light to reduce bacterial burden in pressure ulcers (PUs) in human patients. This research is the first human clinical trial using 222 nm UVC in eradicating bacteria in human wounds. METHOD: Patients with Stage 2 or 3 (as defined by the revised National Pressure Ulcer Advisory Panel Pressure Injury Staging System) sacral or gluteal pressure ulcers (PUs) were subjected to four sessions of 222 nm UVC light therapy over two weeks. Pre- and post-UVC therapy, wound cultures were taken and quantitative analysis of bacterial colony forming units (CFU) were performed. RESULTS: A total of 68 UV light sessions across 16 different patients were conducted. Of these sessions, 59 (87.0%) sessions showed a reduction in CFU counts, with 20 (29.4%) showing complete eradication of bacteria. Bacteria identified included meticillin-resistant Staphylococcus aureus, Pseudomonas aeruginosa and Klebsiella Pneumoniae. The overall median reduction in CFU of the 68 sessions was 78.9%. No adverse events were reported in any of the UV sessions. CONCLUSION: In this study, 222 nm UVC light was safe and effective in reducing bacterial CFU counts in sacral and gluteal PUs across numerous different species of bacteria.

Impact of national interventions to promote responsible antibiotic use: a systematic review.

BACKGROUND: Global recognition of antimicrobial resistance (AMR) as an urgent public health problem has galvanized national and international efforts. Chief among these are interventions to curb the overuse and misuse of antibiotics. However, the impact of these initiatives is not fully understood, making it difficult to assess the expected effectiveness and sustainability of further policy interventions. We conducted a systematic review to summarize existing evidence for the impact of nationally enforced interventions to reduce inappropriate antibiotic use in humans. METHODS: We searched seven databases and examined reference lists of retrieved articles. To be included, articles had to evaluate the impact of national responsible use initiatives. We excluded studies that only described policy implementations. RESULTS: We identified 34 articles detailing interventions in 21 high- and upper-middle-income countries. Interventions addressing inappropriate antibiotic access included antibiotic committees, clinical guidelines and prescribing restrictions. There was consistent evidence that these were effective at reducing antibiotic consumption and prescription. Interventions targeting inappropriate antibiotic demand consisted of education campaigns for healthcare professionals and the general public. Evidence for this was mixed, with several studies showing no impact on overall antibiotic consumption. CONCLUSIONS: National-level interventions to reduce inappropriate access to antibiotics can be effective. However, evidence is limited to high- and upper-middle-income countries, and more evidence is needed on the long-term sustained impact of interventions. There should also be a simultaneous push towards standardized outcome measures to enable comparisons of interventions in different settings.

"Do I need to or do I want to?" A typology of HIV status disclosure among gay, bisexual, and other men who have sex with men.

Gay, bisexual, and other men who have sex with men (GBMSM) are a key population that is disproportionately affected by HIV. However, few studies have explored how and why disclosure of HIV status occurs in this population. To understand disclosure in the context of other socioecological factors, we conducted a qualitative study among 24 self-identified HIV-positive GBMSM, aged 21 and above, and who were Singaporean residents. Analysis of participants' interviews revealed that disclosure of HIV status was not a binary event; rather, each type of disclosure held varying degrees of positive and negative ramifications. Disclosure and self-acknowledgement of HIV status at each time point also had different consequences for participants' quality of life. Suggested potential interventions include increasing training for medical professionals and public awareness surrounding issues relating to HIV. Findings from this study provide a framework to describe the complexities that accompany serostatus disclosure in a setting where there are prevalent "shame-based", negative attitudes towards HIV. As such, this framework can also be utilized in the future planning and organization of services for this target population in similar contexts.

"Not a walking piece of meat with disease": meanings of becoming undetectable among HIV-positive gay, bisexual and other men who have sex with men in the U = U era.

Gay, bisexual and other men who have sex with men (GBMSM) represent a key population disproportionately affected by HIV in various settings. While past studies have investigated how individuals negotiated their identities following their diagnoses of HIV, an emerging area of inquiry considers the implications of viral suppression, or becoming undetectable, on identity and well-being in an undetectable = untransmittable (U = U) era. We conducted 24 in-depth interviews with a purposively recruited sample of GBMSM living with HIV in Singapore. Interviews were analyzed through inductive thematic analysis. Participants viewed viral suppression as a clinical objective, and contrasted this with becoming undetectable as an identity and aspiration. Many participants saw becoming undetectable as a turning point for them post-diagnosis, and expressed a sense of achievement upon attaining the status. Participants shared that being undetectable was associated with several positive outcomes in coming to terms with their HIV-positive diagnoses that signified achievements in health, personal and social responsibilities, as well as equity in romantic and sexual relationships. The results of this study highlight the importance of becoming undetectable and its potential impact on the quality of life for GBMSM living with HIV.