INTRODUCTION: Randomised controlled trials (RCTs) have informed guideline recommendations for the management of stable coronary artery disease (CAD). However, the real-world impact of contemporary guidelines and trials on practising physicians in the Asia-Pacific region remains uncertain. We aimed to evaluate the knowledge, attitudes and practices among cardiovascular physicians in the region regarding stable CAD management. METHOD: An anonymised cross-sectional electronic survey was administered to cardiovascular practitioners from the Asia Pacific, assessing 3 domains: 1) baseline knowledge on recent trials and society guideline, 2) attitudes towards stable CAD, and 3) case scenarios reflecting management preferences. Correlations among knowledge, attitudes and practice scores were assessed between physicians from developed and developing countries using Pearson correlation. RESULTS: Overall, 713 respondents from 21 countries completed the survey. The mean knowledge score was 2.90±1.18 (out of 4), with 37.3% of respondents answering all questions correctly, while 74.6% noted that guidelines have significant impact on their practice. Despite guidelines recommending optimal medical therapy, majority chose revascularisation (range 53.4- 90.6%) as the preferred strategy for the case scenarios. Practitioners from developed regions had higher knowledge scores and lower attitude scores compared to developing regions, while practice scores were similar in both groups. Weakly positive correlations were noted between knowledge, attitude and practice scores. CONCLUSION Variations exist in knowledge and attitudes towards guideline recommendations and correspondingly actual clinical practice in the Asia Pacific, with most practitioners choosing an upfront invasive strategy for the treatment of stable CAD. These differences reflect real-world disparities in guideline interpretation and clinical adoption.
Humans ; Coronary Artery Disease/therapy* ; Cross-Sectional Studies ; Practice Patterns, Physicians'/statistics & numerical data* ; Asia ; Health Knowledge, Attitudes, Practice ; Surveys and Questionnaires ; Male ; Practice Guidelines as Topic ; Female ; Attitude of Health Personnel ; Middle Aged ; Developing Countries

Poly(ADP-ribose) polymerase 1 (PARP1) is a multifunctional protein involved in diverse cellular functions, notably DNA damage repair. Pharmacological inhibition of PARP1 has therapeutic benefits for various pathologies. Despite the increased use of PARP inhibitors, challenges persist in achieving PARP1 selectivity and effective blood-brain barrier (BBB) penetration. The development of a PARP1-specific positron emission tomography (PET) radioligand is crucial for understanding disease biology and performing target occupancy studies, which may aid in the development of PARP1-specific inhibitors. In this study, we leverage the recently identified PARP1 inhibitor, AZD9574, to introduce the design and development of its ¹⁸F-isotopologue ([¹⁸F]AZD9574). Our comprehensive approach, encompassing pharmacological, cellular, autoradiographic, and in vivo PET imaging evaluations in non-human primates, demonstrates the capacity of [¹⁸F]AZD9574 to specifically bind to PARP1 and to successfully penetrate the BBB. These findings position [¹⁸F]AZD9574 as a viable molecular imaging tool, poised to facilitate the exploration of pathophysiological changes in PARP1 tissue abundance across various diseases.

Decalobanthus peltatus is a woody vine that is commonly utilized in traditional Southeast Asian medicinal preparations. Despite the documented therapeutic uses of D. peltatus, there is hardly any information regarding its toxic effects on its consumers. In this study, crude leaf extracts (aqueous, methanol, ethyl acetate, and hexane) from D. peltatus were prepared and evaluated for their embryotoxicity and teratogenic effects. Phytochemical screening of bioactive compounds from the plants showed the presence of alkaloids, flavonoids, saponins, steroids, and tannins. In addition, investigations on the toxicity of the crude leaf extracts were determined using brine shrimp lethality assay, in which the LC50 was calculated. Results showed that the ethyl acetate leaf extract was the most toxic among the crude leaf extracts, with an LC50 of 14.54 ppm. Based on this result, ethyl acetate leaf extract was treated on duck embryos, and the alteration of vascular branching patterns in the chorioallantoic membrane was quantified. Gross morphological and histological analysis of the skin tissues from the treated duck embryos were also examined. We found significant reduction of primary and tertiary vessel diameters in the duck embryos treated with ethyl acetate leaf extracts in both concentrations compared to the control group. Treated duck embryos exhibited gross malformations, growth retardation, and hemorrhages on the external body surfaces at 1000 ppm. Histopathological analysis of the skin tissues from the 14-day-old treated duck embryos showed a reduced number of feather follicles compared to the control group. These results suggest that D. peltatus crude leaf extracts present risks when taken in significant dosages and comprehensive toxicity testing on therapeutic herbs should be performed to ensure their safety on the consumers.

Inflammatory bowel disease encompasses Crohn’s disease and ulcerative colitis and is characterized by uncontrolled, relapsing, and remitting course of inflammation in the gastrointestinal tract. Artificial intelligence represents a new era within the field of gastroenterology, and the amount of research surrounding artificial intelligence in patients with inflammatory bowel disease is on the rise. As clinical trial outcomes and treatment targets evolve in inflammatory bowel disease, artificial intelligence may prove as a valuable tool for providing accurate, consistent, and reproducible evaluations of endoscopic appearance and histologic activity, thereby optimizing the diagnosis process and identifying disease severity. Furthermore, as the applications of artificial intelligence for inflammatory bowel disease continue to expand, they may present an ideal opportunity for improving disease management by predicting treatment response to biologic therapies and for refining the standard of care by setting the basis for future treatment personalization and cost reduction. The purpose of this review is to provide an overview of the unmet needs in the management of inflammatory bowel disease in clinical practice and how artificial intelligence tools can address these gaps to transform patient care.

KMT2B-linked dystonia (DYT-KMT2B) is a childhood-onset dystonia syndrome typically beginning in the lower limbs and progressing caudocranially to affect the upper limbs with eventual prominent craniocervical involvement. Despite its recent recognition, it now appears to be one of the more common monogenic causes of dystonia syndromes. Here, we present an atypical case of DYT-KMT2B with oromandibular dystonia as the presenting feature, which remained restricted to this region three decades after symptom onset. This appears to be the first reported case of DYT-KMT2B from Southeast Asia and provides further supporting evidence for the pathogenic impact of the KMT2B c.6210_6213delTGAG variant.

Some of Vibrio species is well known as pathogenic bacteria in aquaculture and the marine industry. Its infection is able to generate a massive outbreak and affect the fish population, especially for net caged fish such as seabass. This study was conducted to investigate the prevalence of Vibrio spp. isolated from seabass (Lates calcarifer) in Sri Tujuh Lagoon, Tumpat, Kelantan. Then, to determine the antibiotic resistance in Vibrio isolates. Polymerase chain reaction (PCR) was used to detect Vibrio species using specific primer VR169 and VR744 with estimation base pair size band, 597 bp and further identified by sequencing. On the other hand, antibiotic susceptibility tests were continued by using 13 types of antibiotics; kanamycin (K30), chloramphenicol (C30), neomycin (N10), ampicillin (AMP10), nitrofurantoin (F300), tetracycline (TE30), streptomycin (S10), norfloxacin (NOR10), ciprofloxacin (CIP5), nalidixic acid (NA30), gentamicin (CN10), doxycycline (DO30) and sulfamethoxazole (SXT100). As a result, 14 Vibrio isolates were identified, including Vibrio fluvialis (n=6), Vibrio parahaemolyticus (n=3), Vibrio harveyi (n=2) and each isolate for Vibrio vulnificus, Vibrio alginolyticus and Vibrio spp. The results showed that all isolates were sensitive to most antibiotics except ampicillin, neomycin and streptomycin. The MAR index value was ranging from 0 to 0.31. This study demonstrates the prevalence of Vibrio spp. in seabass and the report on multidrug resistance strains that could be of concern to the fish farmers. In addition, data from this study can be further used in fish disease management plans.

Objective: To evaluate a novel polyherbal formulation (BSVT) containing the standardized extracts from the leaves of Boerhavia diffusa, Solidago virgaurea, Vitex negundo, and thymoquinone in CCl4 induced hepatorenal toxicity in rats. Methods: A total of 36 rats were divided into six groups including normal control, CCl4 (2 mL/kg, i.p.), CCl4 (2 mL/kg, i.p.) + Cystone? (750 mg/kg p.o.), CCl4 (2 mL/kg, i.p.) + BSVT (25 mg/kg, p.o.), CCl4 (2 mL/kg, i.p.) + BSVT (50 mg/kg, p.o.), and CCl4 (2 mL/kg, i.p.) + BSVT (100 mg/kg, p.o.). All treatments were given for four weeks. Serum levels of aspartate transaminase, alanine transaminase, alkaline phosphatase, cholesterol, total protein, serum urea, blood urea nitrogen and creatinine were assessed. Superoxide dismutase, malondialdehyde, and glutathione peroxidase were evaluated in tissue homogenate. The histopathological study of liver and kidney tissues was also done. Results: Aspartate transaminase, alanine transaminase, alkaline phosphatase, cholesterol, serum urea, blood urea nitrogen and creatinine were significantly elevated (P<0.001) while total protein was considerably reduced in the CCl4 group as compared to the normal control (P<0.001), which indicated hepatorenal toxicity. In addition, superoxide dismutase and glutathione peroxidase activities were significantly decreased (P<0.001) while malondialdehyde levels were increased markedly (P<0.001). Treatment with BSVT formulation recovered these parameters towards a normal level in a dose-dependent manner. Conclusions: BSVT formulation ameliorates the hepatorenal toxicity in a dose-dependent manner. Furthermore, clinical studies are required to confirm its efficacy.

The complement cascade is a central component of innate immunity which plays a critical role in brain inflammation. Complement C3a receptor (C3aR) is a key mediator of post-ischemic cerebral injury, and pharmacological antagonism of the C3a receptor is neuroprotective in stroke. Cerebral ischemia injures brain endothelial cells, causing blood brain barrier (BBB) disruption which further exacerbates ischemic neuronal injury. In this study, we used an in vitro model of ischemia (oxygen glucose deprivation; OGD) to investigate the protective effect of a C3aR antagonist (C3aRA, SB290157) on brain endothelial cells (bEnd.3). Following 24 hours of reperfusion, OGD-induced cell death was assessed by TUNEL and Caspase-3 staining. Western blot and immunocytochemistry were utilized to demonstrate that OGD upregulates inflammatory, oxidative stress and antioxidant markers (ICAM-1, Cox-2, Nox-2 and MnSOD) in endothelial cells and that C3aRA treatment significantly attenuate these markers. We also found that C3aRA administration restored the expression level of the tight junction protein occludin in endothelial cells following OGD. Interestingly, OGD/reperfusion injury increased the phosphorylation of ERK1/2 and C3aR inhibition significantly reduced the activation of ERK suggesting that endothelial C3aR may act via ERK signaling. Furthermore, exogenous C3a administration stimulates these same inflammatory mechanisms both with and without OGD, and C3aRA suppresses these C3a-mediated responses, supporting an antagonist role for C3aRA. Based on these results, we conclude that C3aRA administration attenuates inflammation, oxidative stress, ERK activation, and protects brain endothelial cells following experimental brain ischemia.
Blood-Brain Barrier ; Blotting, Western ; Brain Ischemia ; Brain ; Caspase 3 ; Cell Death ; Complement C3a ; Complement System Proteins ; Encephalitis ; Endothelial Cells ; Glucose ; Immunity, Innate ; Immunohistochemistry ; In Situ Nick-End Labeling ; In Vitro Techniques ; Inflammation ; Ischemia ; Neurons ; Occludin ; Oxidative Stress ; Phosphorylation ; Reperfusion ; Stroke ; Tight Junctions

Human locomotion involves a complex interplay among multiple brain regions and depends on constant feedback from the visual system. We summarize here the current understanding of the relationship among fixations, saccades, and gait as observed in studies sampling eye movements during locomotion, through a review of the literature and a synthesis of the relevant knowledge on the topic. A significant overlap in locomotor and saccadic neural circuitry exists that may support this relationship. Several animal studies have identified potential integration nodes between these overlapping circuitries. Behavioral studies that explored the relationship of saccadic and gait-related impairments in normal conditions and in various disease states are also discussed. Eye movements and locomotion share many underlying neural circuits, and further studies can leverage this interplay for diagnostic and therapeutic purposes.
Animals ; Brain ; Eye Movements ; Gait ; Humans ; Locomotion ; Posture ; Saccades

BACKGROUND: Many Muslim type 2 diabetes mellitus (T2DM) patients choose to fast the month of Ramadan despite the possible adverse health effects brought about by the change in dietary habits, among other things. Clinical data regarding the safety of multi-drug regimens during fasting are particularly scarce. The aim of the study was to evaluate the safety of a drug protocol devised by the authors to accommodate Ramadan's dietary changes, involving dose adjustments of four anti-diabetic drug regimens in T2DM patients fasting Ramadan. METHODS: In this prospective, observational, open-label study, 301 T2DM patients who wished to fast Ramadan were followed during Ramadan and the preceding month. The incidence of hypoglycemia, diabetic ketoacidosis (DKA) and non-ketotic hyperosmolar state (NKHS) was monitored. Patients were classified into four groups: A group (those taking metformin, sulfonylurea and insulin [n=33]); B group (metformin and sulfonylurea [n=89]); C group (metformin and insulin [n=96]); and D group (premixed 70/30, glargine or regular insulin [n=82]). During Ramadan, drug doses were adjusted as percentages of their pre-Ramadan values: 75% for sulfonylureas, 75% for glargine, 75% for premixed insulin 70/30 in two doses, and 75% for regular insulin. Metformin was adjusted to a twice-daily regimen. RESULTS: No cases of DKA or NKHS were reported. Hypoglycemia occurred at a lower rate than pre-Ramadan values in groups C, and D; and a similar rate in groups A, and B. CONCLUSION: The data suggested that using the above protocol to adjust the doses of anti-diabetic drugs is safe in T2DM patients in regards to hypoglycemia, DKA, and NKHS.
Diabetes Mellitus, Type 2 ; Diabetic Ketoacidosis ; Fasting* ; Food Habits ; Humans ; Hypoglycemia ; Incidence ; Insulin ; Insulin Glargine ; Islam ; Metformin ; Observational Study* ; Prospective Studies