Bombesin receptor subtype-3 (BRS3) is an orphan G protein-coupled receptor (GPCR) that plays critical roles in energy homeostasis, glucose metabolism, and insulin secretion. Recent structural studies have elucidated BRS3 signaling mechanisms using synthetic ligands, including BA1 and MK-5046. However, the molecular basis of BRS3 activation by bioactive natural compounds and their derivatives, particularly those derived from traditional Chinese medicine, remains unclear. Here, we present high-resolution cryogenic electron microscopy (cryo-EM) structures of the human BRS3-G_q complex in both unliganded and active states bound by two herb-derived compounds (DSO-5a and oridonin), at resolutions of 2.9, 2.8, and 2.9 Å, respectively. These structures display distinct ligand recognition patterns between DSO-5a and oridonin. Although both compounds bind to the orthosteric pocket, they differentially engage the interaction network of BRS3, as demonstrated by mutagenesis studies assessing calcium mobilization and inositol phosphate 1 (IP1) accumulation. These findings enhance our understanding of BRS3 activation and provide valuable insights into the development of small-molecule BRS3 modulators with therapeutic potential.

INTRODUCTION

The sudden designation as a COVID-19 Referral Center at the beginning of the pandemic brought about immense change to the Cardiac Catheterization Laboratory (CCL) services of a National Referral Center for tertiary care. As a proactive strategy to determine actions that can be undertaken should an unforeseen event ever happen again, this study was done to explore the impact of COVID-19 to the institution’s CCL caseload, and to review the challenges, innovations and adjustments made by the CCL to become pandemic-capable and crisis-ready.

A qualitative cross-sectional study was conducted, with the first phase describing the CCL census starting from the baseline pre-COVID year of 2019 to the pandemic years of 2020-2022, and the second phase involving Key Informant Interviews (KII) and Focus Group Discussion (FGD) with the hospital and CCL healthcare staff.

The study revealed a large reduction in the urgent, elective and overall number of cases of the CCL in the first year, but has seen a steady increase in subsequent years. Surges of COVID variants were also seen to affect the CCL caseload. The following were noted to be the key elements in the CCL’s transformation to become COVID-19 capable: (a) changes in operations and patient selection, (b) appropriate use of PPE, (c) strict adherence to an infection control protocol, and (d) staffing modifications to reduce infectivity and protect staff availability.

The preparation of the hospital’s CCL to become a pandemic capable laboratory has been difficult and faced many challenges. However, the innovations and adjustments done through efforts and ingenuity of the CCL healthcare team allowed continuous delivery of the highest level of care to patients in spite of the changing pandemic landscape. These changes were duly documented as a basis for response to possible future global and/or national healthcare crises.

Background: and Purpose Intracranial arterial stenosis (ICAS)-related stroke occurs due to three primary mechanisms with distinct infarct patterns: (1) borderzone infarcts (BZI) due to impaired distal perfusion, (2) territorial infarcts due to distal plaque/thrombus embolization, and (3) plaque progression occluding perforators. The objective of the systematic review is to determine whether BZI secondary to ICAS is associated with a higher risk of recurrent stroke or neurological deterioration. Methods: As part of this registered systematic review (CRD42021265230), a comprehensive search was performed to identify relevant papers and conference abstracts (with ≥20 patients) reporting initial infarct patterns and recurrence rates in patients with symptomatic ICAS. Subgroup analyses were performed for studies including any BZI versus isolated BZI and those excluding posterior circulation stroke. The study outcome included neurological deterioration or recurrent stroke during follow-up. For all outcome events, corresponding risk ratios (RRs) and 95% confidence intervals (95% CI) were calculated. Results: A literature search yielded 4,478 records with 32 selected during the title/abstract triage for full text; 11 met inclusion criteria and 8 studies were included in the analysis (n=1,219 patients; 341 with BZI). The meta-analysis demonstrated that the RR of outcome in the BZI group compared to the no BZI group was 2.10 (95% CI 1.52–2.90). Limiting the analysis to studies including any BZI, the RR was 2.10 (95% CI 1.38–3.18). For isolated BZI, RR was 2.59 (95% CI 1.24–5.41). RR was 2.96 (95% CI 1.71–5.12) for studies only including anterior circulation stroke patients. Conclusion This systematic review and meta-analysis suggests that the presence of BZI secondary to ICAS may be an imaging biomarker that predicts neurological deterioration and/or stroke recurrence.

Background and Objectives: The daily interactions of teachers with students allow the former to observe behavioral changes in the latter. This can serve as an opportunity to emphasize teachers' role in mental health interventions in the school setting. This study aimed to provide baseline information regarding high school teachers' mental health literacy specifically on the recognition and referral of students with depression and suicidal behavior. Methodology: The study design was descriptive cross-sectional that included 460 high school teachers from a district in the City of Manila. The modified QualisMental Vignette Scale for depression literacy and Adolescent Suicide Behavior Questionnaire for suicide literacy was adapted as assessment tools. Results and Conclusion Results of the study found that 64% correctly identified depression as a mental health problem in the modified case vignette. The highest proportion of respondents chose 'informing the parents' as their preferred mode of referral system. The teachers had varying levels of knowledge on suicidal behaviors. More mental health literacy interventions focusing on depression and suicide must be conducted among teachers to improve their competency on these topics.
Depression ; Suicidal Ideation ; Mental Health

We previously demonstrated that endogenous phosphatidic acid (PA) promotes liver regeneration after acetaminophen (APAP) hepatotoxicity. Here, we hypothesized that exogenous PA is also beneficial. To test that, we treated mice with a toxic APAP dose at 0 h, followed by PA or vehicle (Veh) post-treatment. We then collected blood and liver at 6, 24, and 52 h. Post-treatment with PA 2 h after APAP protected against liver injury at 6 h, and the combination of PA and

INTRODUCTION: Child sexual abuse (CSA) adversely affects a child's growth and well-being. This study aimed to describe the profile of children presenting to a tertiary paediatric emergency department(ED) with CSA. METHODS: Children 0-16 years old presenting to KK Women's and Children's Hospital ED from June 2016 to August 2020 with sexual abuse were retrospectively reviewed. We performed a secondary analysis on girls and stratified them by age <13 and ≥13 years old. RESULTS: There were 790 patients who made 833 visits for CSA. Victims were predominantly girls (747, 94.8%) and perpetrators were predominantly men (763, 96.6%). The abuse first occurred before the age of 13 years in 315 victims (39.9%). For 468 (59.2%), more than one incident occurred before presentation. Compared to girls ≥13 years old, girls <13 years old were more frequently abused by a family member (47.7% versus 8.0%, CONCLUSION The findings highlight common characteristics of CSA cases, and can aid the future identification and protection of vulnerable children. The fact that most children presented after more than one incident suggests the need to more closely monitor and protect potentially at-risk children.
Adolescent ; Child ; Child Abuse ; Child Abuse, Sexual ; Child, Preschool ; Emergency Service, Hospital ; Female ; Humans ; Infant ; Infant, Newborn ; Male ; Parents ; Retrospective Studies

Locally advanced non-small cell lung cancer (NSCLC) continues to be a challenging disease to treat. With high rates of both local and distant failures, there is significant interest in finding more biologically active chemotherapy regimens that can contribute to reduce both failures. The phase III PROCLAIM trial, recently published in the Journal of Clinical Oncology entitled“PROCLAIM: randomized phase III trial of pemetrexed–cisplatin or etoposide–cisplatin plus thoracic radiation therapy followed by consolidation chemotherapy in locally advanced nonsquamous non-small-cell lung cancer”, compared two different chemotherapy regimens given concurrently with radiotherapy in patients with stage III non-squamous lung cancer: pemetrexed plus cisplatin versus cisplatin plus etoposide. Both groups received con-solidation chemotherapy. After enrolling 598 of planned 600 patients, the study was stopped early due to futility as no difference was seen in the primary end-point of overall survival. Since PROCLAIM was designed as a superiority trial, these results suggest that pemetrexed regimens do not offer a clinical advantage over standard cisplatin plus etopo-side. There are some subpopulations who might still benefit from pemetrexed, especially if clinicians are concerned about myelosuppression-related adverse events. Future trials are needed to investigate novel biologic agents and irradiation techniques that can result in more durable local and distant disease control in locally advanced NSCLC.

BACKGROUND: Overweight, obesity, and cardiovascular disease risk factors are prevalent among firefighters in some developed countries. It is unclear whether physical activity and cardiopulmonary fitness reduce cardiovascular disease risk and the cardiovascular workload at work in firefighters. The present study investigated the relationship between leisure-time physical activity, cardiopulmonary fitness, cardiovascular disease risk factors, and cardiovascular workload at work in firefighters in Hong Kong. METHODS: Male firefighters (n = 387) were randomly selected from serving firefighters in Hong Kong (n = 5,370) for the assessment of cardiovascular disease risk factors (obesity, hypertension, diabetes mellitus, dyslipidemia, smoking, known cardiovascular diseases). One-third (Target Group) were randomly selected for the assessment of off-duty leisure-time physical activity using the short version of the International Physical Activity Questionnaire. Maximal oxygen uptake was assessed, as well as cardiovascular workload using heart rate monitoring for each firefighter for four "normal" 24-hour working shifts and during real-situation simulated scenarios. RESULTS: Overall, 33.9% of the firefighters had at least two cardiovascular disease risk factors. In the Target Group, firefighters who had higher leisure-time physical activity had a lower resting heart rate and a lower average working heart rate, and spent a smaller proportion of time working at a moderateintensity cardiovascular workload. Firefighters who had moderate aerobic fitness and high leisuretime physical activity had a lower peak working heart rate during the mountain rescue scenario compared with firefighters who had low leisure-time physical activities. CONCLUSION: Leisure-time physical activity conferred significant benefits during job tasks of moderate cardiovascular workload in firefighters in Hong Kong.
Cardiovascular Diseases ; Developed Countries ; Diabetes Mellitus ; Dyslipidemias ; Firefighters* ; Heart Rate ; Hong Kong ; Humans ; Hypertension ; Leisure Activities* ; Male ; Motor Activity* ; Obesity ; Overweight ; Oxygen ; Risk Factors* ; Smoke ; Smoking

Background: The incidence of diabetes mellitus is ever increasing. Individuals with diabetes mellitus may have concurrent mental health disorders and are shown to have poorer disease outcomes. The objectives of this study were to determine the prevalence of depression, anxiety and stress (DAS) in diabetes patients aged 20 years or more in the primary care setting. Methods: This was a cross-sectional study involving the use of self-administered questionnaire conducted in eight primary care private and government clinics in Pulau Pinang and Melaka, Malaysia. The validated DASS-21 questionnaire was used as a screening tool for the symptoms of DAS. Prior permission was obtained from the patients and, clearance from ethical committee was obtained before the start of the study. Data analysis was done using SPSS statistical software. Results: A total of 320 patients with diabetes from eight centres were enrolled via convenience sampling. Sample size was calculated using the Kish’s formula. The prevalence of DAS among patients with diabetes from our study was 26.6%, 40% and 19.4%, respectively. Depression was found to be significantly associated with marital status and family history of DAS; anxiety was significantly associated with monthly household income, presence of co-morbidities and family history of DAS; and stress was significantly associated with occupation and family history of DAS. Conclusions: The prevalence of DAS was higher in patients with diabetes compared with the general community. We recommend to routinely screen all patients with diabetes using the DASS-21 questionnaire because it is easy to perform and inexpensive.

There have been many clinical trials conducted to evaluate novel systemic regimens for unresectable pancreatic cancer. However, most of the trial results were negative, and gemcitabine monotherapy has remained the standard systemic treatment for years. A number of molecular targeted agents, including those against epidermal growth factor receptor and vascular endothelial growth factor receptors, have also been tested. In recent years, there have been some breakthroughs in the deadlock: three regimens, namely gemcitabine-erlotinib, FOLFIRINOX, and gemcitabine-nab-paclitaxel, have been shown to prolong the overall survival of patients when compared with gemcitabine monotherapy. In addition, emerging data suggested that the membrane protein human equilibrative nucleotide transporter 1 is a potential biomarker with which to predict the efficacy of gemcitabine. Here we review the literature on the development of systemic agents for pancreatic cancer, discuss the current choices of treatment, and provide future directions on the development of novel agents.
Adenocarcinoma ; drug therapy ; Albumins ; Antineoplastic Combined Chemotherapy Protocols ; therapeutic use ; Camptothecin ; analogs & derivatives ; Deoxycytidine ; analogs & derivatives ; Equilibrative Nucleoside Transporter 1 ; Erlotinib Hydrochloride ; Fluorouracil ; Humans ; Leucovorin ; Organoplatinum Compounds ; Paclitaxel ; Pancreatic Neoplasms ; drug therapy ; Quinazolines ; Receptor, Epidermal Growth Factor ; Receptors, Vascular Endothelial Growth Factor