The clinical and geographical characteristics, health-seeking behaviours of ST-segment elevation myocardial infarction patients with their total ischaemic time and short-term cardiac mortality outcomes: a local geographical perspective from a developing country.

INTRODUCTION: Ischaemic heart disease including ST-segment elevation myocardial infarction (STEMI) is the leading cause of death among Malaysians. Total ischaemic time (TIT) which consists of patient delay and systemic delay is a strong predictor of cardiovascular outcome in STEMI. Primary percutaneous coronary intervention (PPCI) is superior to medical thrombolysis in improving STEMI patients' survival outcomes. Our study aims to provide an insight into the clinical and geographical characteristics of STEMI patients, their health-seeking behaviour, TIT, interventions received and short-term cardiac mortality outcomes in the effort to improve the existing coronary care service. MATERIALS AND METHODS: This is a descriptive study looking into patients who were diagnosed with STEMI and presented to or were referred to Sarawak Heart Centre between 1st July 2022 and 31st December 2022. RESULTS: A total of 183 patients were recruited and 33.3% were <50 years old. The majority were in a different division during symptom onset from where the local PPCI centre is located and some underwent one or two transits before arrival at the revascularisation centre. More presented outof- hour and they were more likely to present within the PPCI window. The median TIT for the study population was 3.3 hours. The short-term cardiac mortalities were 9.3% and only the Killip class was found to have a significant association. In this study, TIT was not significantly associated with short-term mortalities but those who died had a longer median TIT. CONCLUSION: A local STEMI network should be set up using the 'Hub-and-Spoke' model in a staged-wise approach to reduce TIT given that PPCI is now the gold standard of treatment alongside continuous effort in patient education.

Incidence of fragility hip fracture across the Asia-pacific region: A systematic review.

PURPOSE: This systematic review aimed to update fragility hip fracture incidences in the Asia Pacific, and compare rates between countries/regions. METHOD: A systematic search was conducted in four electronic databases. Studies reporting data between 2010 and 2023 on the geographical incidences of hip fractures in individuals aged ≥50 were included. Exclusion criteria were studies reporting solely on high-trauma, atypical, or periprosthetic fractures. We calculated the crude incidence, age- and sex-standardised incidence, and the female-to-male ratio. The systematic review was registered with PROSPERO (CRD42020162518). RESULTS: Thirty-eight studies were included across nine countries/regions (out of 41 countries/regions). The crude hip fracture incidence ranged from 89 to 341 per 100,000 people aged ≥50, with the highest observed in Australia, Taiwan, and Japan. Age- and sex-standardised rates ranged between 90 and 318 per 100,000 population and were highest in Korea and Japan. Temporal decreases in standardised rates were observed in Korea, China, and Japan. The female-to-male ratio was highest in Japan and lowest in China. CONCLUSION: Fragility hip fracture incidence varied substantially within the Asia-Pacific region. This observation may reflect actual incidence differences or stem from varying research methods and healthcare recording systems. Future research should use consistent measurement approaches to enhance international comparisons and service planning.

Impact of a novel pre-hospital stroke notification programme on acute stroke care key performance indicators in Hong Kong: a multicentre prospective cohort study with historical controls.

INTRODUCTION: Early identification and initiation of reperfusion therapy is essential for suspected acute ischaemic stroke. A pre-hospital stroke notification (PSN) protocol using FASE (facial drooping, arm weakness, speech difficulties, and eye palsy) was implemented to improve key performance indicators (KPIs) in acute stroke care delivery. We assessed KPIs and clinical outcomes before and after PSN implementation in Hong Kong. METHODS: This prospective cohort study with historical controls was conducted in the Accident and Emergency Departments of four public hospitals in Hong Kong. Patients were screened using the PSN protocol between August 2021 and February 2022. Suspected stroke patients between August 2020 and February 2021 were included as historical controls. Door-to-needle (DTN) and door-to-computed tomography (DTC) times before and after PSN implementation were compared. Clinical outcomes including National Institutes of Health Stroke Scale score at 24 hours and modified Rankin Scale score at 3 months after intravenous recombinant tissue-type plasminogen activator (IV-rtPA) were also assessed. RESULTS: Among the 715 patients (266 PSN and 449 non-PSN) included, 50.8% of PSN patients and 37.7% of non-PSN patients had a DTC time within 25 minutes (P<0.001). For the 58 PSN and 134 non-PSN patients given IV-rtPA, median DTN times were 67 and 75.5 minutes, respectively (P=0.007). The percentage of patients with a DTN time within 60 minutes was higher in the PSN group than in the non-PSN group (37.9% vs 21.6%; P=0.019). No statistically significant differences in clinical outcomes were observed. CONCLUSION: Although the PSN protocol shortened DTC and DTN times, clinical outcomes did not significantly differ.

Designing an App to Support Measurement-Based Peer Supervision of Frontline Health Workers Delivering Brief Psychosocial Interventions in Texas: Multimethod Study.

BACKGROUND: The unmet need for mental health care affects millions of Americans. A growing body of evidence in implementation science supports the effectiveness of task sharing in the delivery of brief psychosocial interventions. The digitization of training and processes supporting supervision can rapidly scale up task-shared interventions and enable frontline health workers (FLWs) to learn, master, and deliver interventions with quality and support. OBJECTIVE: We aimed to assess the perceived feasibility and acceptability of a novel mobile and web app designed and adapted to support the supervision, training, and quality assurance of FLWs delivering brief psychosocial interventions. METHODS: We followed human-centered design principles to adapt a prototype app for FLWs delivering brief psychosocial interventions for depression, drawing from an app previously designed for use in rural India. Using a multimethod approach, we conducted focus group sessions comprising usability testing and group interviews with FLWs recruited from a large health system in Texas to assess the feasibility and acceptability of the app. The positive System Usability Scale was used to determine the app's overall usability. We also calculated the participants' likelihood of recommending the app to others using ratings of 0 to 10 from least to most likely (net promoter score). Focus group transcripts were coded and analyzed thematically, and recommendations were summarized across 4 key domains. RESULTS: A total of 18 FLWs varying in role and experience with client care participated in the study. Participants found the app to be usable, with an average System Usability Scale score of 72.5 (SD 18.1), consistent with the industry benchmark of 68. Participants' likelihood of recommending the app ranged from 5 to 10, yielding a net promoter score of 0, indicating medium acceptability. Overall impressions of the app from participants were positive. Most participants (15/18, 83%) found the app easy to access and navigate. The app was considered important to support FLWs in delivering high-quality mental health care services. Participants felt that the app could provide more structure to FLW training and supervision processes through the systematic collection and facilitation of performance-related feedback. Key concerns included privacy-related and time constraints regarding implementing a separate peer supervision mechanism that may add to FLWs' workloads. CONCLUSIONS: We designed, built, and tested a usable, functional mobile and web app prototype that supports FLW-delivered psychosocial interventions in the United States through a structured supervision mechanism and systematic collection and review of performance measures. The app has the potential to scale the work of FLWs tasked with delivering these interventions to the hardest-to-reach communities they serve. The results of this project will inform future work to evaluate the app's use and efficacy in real-world settings to support task-shared mental health programs across the United States.

Factors associated with in-hospital mortality among infective endocarditis patients.

INTRODUCTION: Despite recent advancements in the diagnosis and management of infective endocarditis (IE), it is associated with substantial morbidity and mortality. Our study objective is to determine the factors associated with in-hospital mortality in IE patients among the local population. MATERIALS AND METHODS: All IE patients who were diagnosed with definite or possible IE and were treated at Sarawak Heart Centre from 1st January 2020 to 31st December 2022 were recruited. We examined the demographic features of the subjects and the factors that contributed to in-hospital mortality. Multivariate logistic regression was used to analyse the associated factors and in-hospital mortality. RESULTS: Our study population comprised a total of 37 patients with a mean age of 46.4 years and male predominance. The in-hospital mortality rate of IE in this study was 44.4%. Haemodynamic instability and anaemia were found to be strong predictors of IE survival outcome, with an odds ratio of 51.5 and 35.7 respectively. Patients with vascular phenomenon and heart failure were at 10.5- and 6.0-times higher odds of dying, however, these two associations were found to be not statistically significant. CONCLUSION: The in-hospital mortality due to IE in our study was among the highest in developing countries. Factors of hypotension and optimal response to individual hemodynamic parameters may confer lower mortality. While anaemia is demonstrable as a risk factor for inpatient mortality, a target has yet to be reasonably established.

Not always an innocent bystander: the impact of stabilised phosphopantetheine moieties when studying nonribosomal peptide biosynthesis.

Nonribosomal peptide synthetases produce many important peptide natural products and are centred around carrier proteins (CPs) that deliver intermediates to various catalytic domains. We show that the replacement of CP substrate thioesters by stabilised ester analogues leads to active condensation domain complexes, whereas amide stabilisation generates non-functional complexes.

A Chemoenzymatic Approach to Investigate Cytochrome P450 Cross-Linking in Glycopeptide Antibiotic Biosynthesis.

Glycopeptide antibiotics (GPAs) are important and medically relevant peptide natural products. In the context of antimicrobial resistance (AMR), understanding and manipulating GPA biosynthesis is essential to discover new bioactive derivatives of these peptides. Among all the enzymatic steps in GPA biosynthesis, the most complex occurs during the maturation (cross-linking) of the peptide aglycone. This is achieved-while the peptide remains attached to the nonribosomal peptide synthetase (NRPS) machinery-through the action of a cytochrome P450 (CYP450 or Oxy)-mediated cyclization cascade. There is great interest in understanding the formation of the cross-links between the aromatic side chains in GPAs as this process leads to the cup-shaped aglycone, which is itself a requirement for antibiotic activity. In this regard, the use of in vitro experiments is crucial to study this process. To address the process of peptide cyclization during GPA biosynthesis, a series of peptide substrates and different Oxy enzymes are required. In this chapter, we describe a practical and efficient route for the synthesis of peptidyl-CoAs, the expression of proteins/enzymes involved in the in vitro cyclization assay, the loading of the PCP with peptidyl-CoAs, an optimized CYP450-mediated cyclization cascade and assay workup followed by mass spectrometry (MS) characterization. This in vitro assay affords high conversion to cyclic peptides and demonstrates the tolerance of the P450s for novel GPA precursor peptide substrates.

Highlights from the Tenth International Workshop on HIV Persistence during Therapy, December 13-16, 2022, Miami, Florida-USA.

The International Workshop on HIV Persistence during Therapy provides a forum in which HIV/AIDS researchers gather to share the latest research findings related to viral reservoirs and cure. The Tenth Workshop, which was attended by over 400 delegates, extended over 4 days and comprised eight sessions covering topics from the basic science of viral persistence to therapeutic approaches to HIV cure. Furthermore, satellite sessions on the first day of the Conference featuring cure research endeavours being pursued by the Bill and Melinda Gates Foundation as well as those being coordinated under the National Institutes of Health Martin Delaney Collaboratory program, provided important updates on research advances being made in these initiatives. As with previous conferences, the International Workshop on HIV Persistence during Therapy is primarily abstract-driven with only one invited talk for each of the sessions. This format, therefore, increases the number of presentations from early-stage investigators. Furthermore, presentations by Community representatives illustrated approaches to creating cure research literacy with effective messaging for the Community. The following article offers a synopsis of the meeting sessions. Due to space constraints, some presentations may have only been briefly discussed. Nevertheless, the Workshop abstracts can be found online (https://www/sciencedirect.com/journal/journal-of-virus-eradication/vol/8/suppl/S).

Anti-methicillin resistance Staphylococcus aureus and in vitro toxicology evaluation of corilagin-loaded gelatin/agar microspheres with potential biotextile applications.

Methicillin-resistant Staphylococcus aureus (MRSA) has emerged since the early 1960s. The increasing resistance of pathogens to currently used antibiotics requires the urgent discovery of new antimicrobials effective in combating drug-resistant bacteria. From past to present, medicinal plants are useful to cure human diseases. Corilagin (ß-1-O-galloyl-3,6-(R)-hexahydroxydiphenoyl-d-glucose), commonly found in Phyllanthus species, exerts potentiating effect on ß-lactams against MRSA. However, its biological effect may not be fully utilized. Therefore, incorporating microencapsulation technology with the delivery of corilagin would be more effective in utilizing the potential effect on biomedical applications. This work reports the development of a safe micro-particulate system which combined agar with gelatin as wall matrix materials for topical delivery of corilagin in order to eliminate the potential toxicity of the crosslinker formaldehyde. The optimal parameters for microsphere preparation were identified and the particle size of optimal microspheres was 20.11 µm ± 3.58. Antibacterial studies revealed that micro-trapped corilagin (minimum bactericidal concentration, MBC = 0.5 mg/mL) possessed a higher potency against MRSA than free corilagin (MBC = 1 mg/mL). The in vitro skin cytotoxicity showed the safety of the corilagin-loaded microspheres for topical applications, with approximately 90 % of HaCaT cell viability. Our results demonstrated the potential of corilagin-loaded gelatin/agar microspheres for the applicable bio-textile products to treat drug-resistant bacterial infections.

Characteristics of patients with tuberculosis and the associated factors with TB-related mortality in a rural setting in Sarawak, Malaysia: A single-centre study.

INTRODUCTION: Tuberculosis (TB) in Malaysia has estimated incidence and mortality rates of 81 cases per 100,000 people-year and 4.9 per 100,000 populations, respectively. This study aimed to study the characteristics of rural TB patients and their mortality outcomes. MATERIALS AND METHODS: This is a retrospective observational study involving real-world data analysis, looking into TB patients in Lubok Antu Health Clinic by obtaining data through clinic cards, from 1 January 2019 till 31 December 2020. Statistical significance was p < 0.05. RESULTS: Eighty-four patients were included. Fifty-two (61.9%) were male. Median age was 58.5 (39-67). Forty-six (54.8%) had smear-positive TB. Seventy-eight (92.9%) were alive at treatment completion. Fifteen (17.9%) experienced adverse drug reactions. Estimated prevalence and mortality rate were 7.1% and 10.7 per 100,000 populations, respectively. Regression analyses revealed that drug reaction was significantly associated with compliance [OR = 8.38 (95% CI: 1.26, 55.53), p = 0.029]. Patients compliant with treatment were more likely to survive [OR = 12.5 (95% CI: 1.61, 97.34), p = 0.028]. CONCLUSION: Compliance with TB treatment should be emphasised to reduce TB-related mortality.

"I Have to Ask": A Mixed-Methods Study on the Collection of Sexual Orientation and Gender Identity Data Within the San Francisco County COVID-19 Case Investigation and Contact Tracing Program.

OBJECTIVE: To understand how the San Francisco (SF) COVID-19 case investigation and contact tracing (CICT) workforce documented sexual orientation and gender identity (SOGI) data, as well as a qualitative assessment of the workforce's capacity to successfully collect that data. METHODS: This mixed-methods project analyzed data from 2 sources: SOGI item completeness among adult completed/partially completed interviews in the SF digital CICT COVID-19 database, and a secondary data analysis of qualitative data from 16 semistructured 90-minute virtual interviews with the SF CICT workforce, between November 14, 2020, and April 14, 2021. RESULTS: Among 15 416 COVID-19 cases and 7836 close contacts, sexual orientation data are missing from 20% of cases and 17% of contacts. The proportion of transgender/nonbinary individuals was 0.32% and 0.5%, respectively. The SF CICTs participants discussed challenges in collecting SOGI data, not understanding SOGI measure rationale, and feeling uncomfortable asking the questions. CONCLUSION: Qualitative interviews with the COVID-19 CICT workforce and quantitative data on SOGI parameters in COVID-19 surveillance suggest that these data may have been underreported. Our results strongly suggest that comprehensive training is crucial in the collection of SOGI data among COVID-19 cases and their close contacts. If SOGI data are not collected accurately, the true impact of COVID-19 among lesbian, gay, bisexual, transgender, and queer populations remains unknown, preventing data-driven allocation of COVID-19 funds to lesbian, gay, bisexual, transgender, and queer communities.

Chemoselective Methionine Labelling of Recombinant Trastuzumab Shows High In Vitro and In Vivo Tumour Targeting.

A highly effective 2-step system for site-specific antibody modification and conjugation of the monoclonal antibody Herceptin (commercially available under Trastuzumab) in a cysteine-independent manner was used to generate labelled antibodies for in vivo imaging. The first step contains redox-activated chemical tagging (ReACT) of thioethers via engineered methionine residues to introduce specific alkyne moieties, thereby offering a novel easy way to fundamentally change the process of antibody bioconjugation. The second step involves modification of the introduced alkyne via azide-alkyne cycloaddition 'click' conjugation. The versatility of this 2-step approach is demonstrated here by the selective incorporation of a fluorescent dye but can also be applied to a wide variety of different conjugation partners depending on the desired application in a facile manner. Methionine-modified antibodies were characterised in vitro, and the diagnostic potential of the most promising variant was further analysed in an in vivo xenograft animal model using a fluorescence imaging modality. This study demonstrates how methionine-mediated antibody conjugation offers an orthogonal and versatile route to the generation of tailored antibody conjugates with in vivo applicability.

Exploring the Flexibility of the Glycopeptide Antibiotic Crosslinking Cascade for Extended Peptide Backbones.

The glycopeptide antibiotics (GPAs) are a clinically approved class of antimicrobial agents that classically function through the inhibition of bacterial cell-wall biosynthesis by sequestration of the precursor lipid II. The oxidative crosslinking of the core peptide by cytochrome P450 (Oxy) enzymes during GPA biosynthesis is both essential to their function and the source of their synthetic challenge. Thus, understanding the activity and selectivity of these Oxy enzymes is of key importance for the future engineering of this important compound class. Recent reports of GPAs that display an alternative mode of action and a wider range of core peptide structures compared to classic lipid II-binding GPAs raises the question of the tolerance of Oxy enzymes for larger changes in their peptide substrates. In this work, we explore the ability of Oxy enzymes from the biosynthesis pathways of lipid II-binding GPAs to accept altered peptide substrates based on a vancomycin template. Our results show that Oxy enzymes are more tolerant of changes at the N terminus of their substrates, whilst C-terminal extension of the peptide substrates is deleterious to the activity of all Oxy enzymes. Thus, future studies should prioritise the study of Oxy enzymes from atypical GPA biosynthesis pathways bearing C-terminal peptide extension to increase the substrate scope of these important cyclisation enzymes.

Charge Stability and Charge-State-Based Spin Readout of Shallow Nitrogen-Vacancy Centers in Diamond.

Spin-based applications of the negatively charged nitrogen-vacancy (NV) center in diamonds require an efficient spin readout. One approach is the spin-to-charge conversion (SCC), relying on mapping the spin states onto the neutral (NV0) and negative (NV-) charge states followed by a subsequent charge readout. With high charge-state stability, SCC enables extended measurement times, increasing precision and minimizing noise in the readout compared to the commonly used fluorescence detection. Nanoscale sensing applications, however, require shallow NV centers within a few nanometers distance from the surface where surface related effects might degrade the NV charge state. In this article, we investigate the charge state initialization and stability of single NV centers implanted ≈5 nm below the surface of a flat diamond plate. We demonstrate the SCC protocol on four shallow NV centers suitable for nanoscale sensing, obtaining a reduced readout noise of 5-6 times the spin-projection noise limit. We investigate the general applicability of the SCC for shallow NV centers and observe a correlation between the NV charge-state stability and readout noise. Coating the diamond with glycerol improves both the charge initialization and stability. Our results reveal the influence of the surface-related charge environment on the NV charge properties and motivate further investigations to functionalize the diamond surface with glycerol or other materials for charge-state stabilization and efficient spin-state readout of shallow NV centers suitable for nanoscale sensing.

A Digital Platform to Support HIV Case Management for Youth and Young Adults: Mixed Methods Feasibility Study.

BACKGROUND: Advances in medical treatments in recent years have contributed to an overall decline in HIV-related opportunistic infections and deaths in youth; however, mortality and morbidity rates in perinatally and nonperinatally infected adolescents and young adults (AYA) living with HIV remain relatively high today. OBJECTIVE: The goal of this project was to assess the use, utility, and cost-effectiveness of PlusCare, a digital app for HIV case management in AYA living with HIV. The app supports routine case management tasks, such as scheduling follow-up visits, sharing documents for review and signature, laboratory test results, and between-visit communications (eg, encouraging messages). METHODS: We conducted a single-group mixed methods pre-post study with HIV case management programs in 2 large urban hospitals in the Boston metro area. Case management staff (case managers [CMs], N=20) and AYA living with HIV participants (N=45) took part in the study with access to PlusCare for up to 15 and 12 months, respectively. RESULTS: The CMs and AYA living with HIV reported mean System Usability Scale scores of 51 (SD 7.9) and 63 (SD 10.6), respectively. Although marginally significant, total charges billed at 1 of the 2 sites compared with the 12 months before app use (including emergency, inpatient, and outpatient charges) decreased by 41% (P=.046). We also observed slight increases in AYA living with HIV self-reported self-efficacy in chronic disease management and quality of life (Health-Related Quality of Life-4) from baseline to the 12-month follow-up (P=.02 and P=.03, respectively) and increased self-efficacy from the 6- to 12-month follow-up (P=.02). There was no significant change in HIV viral suppression, appointment adherence, or medication adherence in this small-sample pilot study. CONCLUSIONS: Although perceived usability was low, qualitative feedback from CMs and use patterns suggested that direct messaging and timely, remote, and secure sharing of laboratory results and documents (including electronic signatures) between CMs and AYA living with HIV can be particularly useful and have potential value in supporting care coordination and promoting patient self-efficacy and quality of life. TRIAL REGISTRATION: ClinicalTrials.gov NCT03758066; https://clinicaltrials.gov/ct2/show/NCT03758066.

IgG fractions from patients with antiphospholipid syndrome and systemic lupus erythematosus bind to platelets, but do not affect collagen-induced platelet activation.

Anti-beta-2 glycoprotein 1 (anti-ß2GP1) is an antiphospholipid antibody found in patients with antiphospholipid syndrome (APS) and systemic lupus erythematosus (SLE). Its presence commonly is associated with thrombosis; however, the mechanisms of interaction of anti-ß2GP1 antibodies and platelets remain unclear. We investigated the effects of APS and SLE patient-derived IgG fractions on collagen-mediated platelet aggregation and examined the binding of patient-derived IgG to platelets before and after activation by collagen. IgG fractions, 150, 200, 300 or 350 µg/ml, isolated from 11 patients with APS and SLE were incubated with two sets of platelet-rich plasma (PRP) in the incubation wells of an aggregometer. The first set was activated by collagen and the other set was incubated for an additional 10 min. All platelets were collected by centrifugation and fixed in cell blocks. We assessed binding of IgG to platelets using immunocytochemistry (ICC). Patient-derived IgG fractions did not affect collagen-induced platelet aggregation. ICC staining using anti-human IgG antibodies demonstrated that patient-derived IgG fractions had greater affinity for non-activated platelets than those activated by 0.75 µg/ml collagen. Patient-derived IgG fractions bound to the surface of platelets and potentially could be internalized by platelets. IgG fractions from APS and SLE patients may sensitize non-activated platelets, which could increase platelet reactivity and thrombotic risk in patients. We did not detect secondary effects of patient-derived IgG fractions.