The impact of obesity: a narrative review

Obesity is a disease with a major negative impact on human health. However, people with obesity may not perceive their weight to be a significant problem and less than half of patients with obesity are advised by their physicians to lose weight. The purpose of this review is to highlight the importance of managing overweight and obesity by discussing the adverse consequences and impact of obesity. In summary, obesity is strongly related to >50 medical conditions, with many of them having evidence from Mendelian randomisation studies to support causality. The clinical, social and economic burdens of obesity are considerable, with these burdens potentially impacting future generations as well. This review highlights the adverse health and economic consequences of obesity and the importance of an urgent and concerted effort towards the prevention and management of obesity to reduce the burden of obesity.

A summary of the Malaysian Clinical Practice Guidelines on the management of postmenopausal osteoporosis, 2022

Objectives@#The aim of these Clinical Practice Guidelines is to provide evidence-based recommendations to assist healthcare providers in the screening, diagnosis and management of patients with postmenopausal osteoporosis (OP). @*Methods@#A list of key clinical questions on the assessment, diagnosis and treatment of OP was formulated. A literature search using the PubMed, Medline, Cochrane Databases of Systematic Reviews, and OVID electronic databases identified all relevant articles on OP based on the key clinical questions, from 2014 onwards, to update from the 2015 edition. The articles were graded using the SIGN50 format. For each statement, studies with the highest level of evidence were used to frame the recommendation. @*Results@#This article summarizes the diagnostic and treatment pathways for postmenopausal OP. Risk stratification of patients with OP encompasses clinical risk factors, bone mineral density measurements and FRAX risk estimates. Non-pharmacological measures including adequate calcium and vitamin D, regular exercise and falls prevention are recommended. Pharmacological measures depend on patients’ fracture risk status. Very high-risk individuals are recommended for treatment with an anabolic agent, if available, followed by an anti-resorptive agent. Alternatively, parenteral anti-resorptive agents can be used. High-risk individuals should be treated with anti-resorptive agents. In low-risk individuals, menopausal hormone replacement or selective estrogen receptor modulators can be used, if indicated. Patients should be assessed regularly to monitor treatment response and treatment adjusted, as appropriate. @*Conclusions@#The pathways for the management of postmenopausal OP in Malaysia have been updated. Incorporation of fracture risk stratification can guide appropriate treatment.

RESISTANCE CONFERRING MUTATIONS IN SARS-CoV-2 DELTA FOLLOWING SOTROVIMAB INFUSION

Several Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) neutralising monoclonal antibodies (mAbs) have received emergency use authorisation by regulatory agencies for treatment and prevention of Coronavirus Disease 2019 (COVID-19), including in patients at risk for progression to severe disease. Here we report the persistence of viable SARS-CoV-2 in patients treated with sotrovimab and the rapid development of spike gene mutations that have been shown to confer high level resistance to sotrovimab in vitro. We highlight the need for SARS-CoV-2 genomic surveillance in at risk individuals to inform stewardship of mAbs use and prevent potential treatment failures.

Peganum harmala Extract Has Antiamoebic Activity to Acanthamoeba triangularis Trophozoites and Changes Expression of Autophagy-Related Genes.

Peganum harmala, a well-known medicinal plant, has been used for several therapeutic purposes as it contains numerous pharmacological active compounds. Our study reported an anti-parasitic activity of P. harmala seed extract against Acanthamoeba triangularis. The stress induced by the extract on the surviving trophozoites for Acanthamoeba encystation and vacuolization was examined by microscopy, and transcriptional expression of Acanthamoeba autophagy-related genes was investigated by quantitative PCR. Our results showed that the surviving trophozoites were not transformed into cysts, and the number of trophozoites with enlarged vacuoles were not significantly different from that of untreated control. Molecular analysis data demonstrated that the mRNA expression of tested AcATG genes, i.e., ATG3, ATG8b, and ATG16, was at a basal level along the treatment. However, upregulation of AcATG16 at 24 h post treatment was observed, which may indicate an autophagic activity of this protein in response to the stress. Altogether, these data revealed the anti-Acanthamoeba activity of P. harmala extract and indicated the association of autophagy mRNA expression and cyst formation under the extract stress, representing a promising plant for future drug development. However, further identification of an active compound and a study of autophagy at the protein level are needed.

Comparison of tissue and molecular yield between fine-needle biopsy (FNB) and fine-needle aspiration (FNA): a randomized study.

Background and study aims Recently, a new Franseen design endoscopic ultrasound-guided fine-needle biopsy (EUS-FNB) needle was developed with the goal of providing more tissue for histology. We compared the tissue adequacy rate and nucleic acid yield of 22G EUS-FNB vs. 22G endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA), in solid gastrointestinal and extra-intestinal lesions. Patients and methods We conducted a randomized crossover study and recruited 36 patients. We performed three passes for pancreatic lesions and two passes for other lesions, using each needle. We blinded the pathologist to needle assignment. We assessed the diagnostic tissue adequacy rate and compared the total tissue area, diagnostic tissue area, and desmoplastic stroma (DS) area in cases of carcinoma. We also examined the nucleic acid yield of the two needles in pancreatic lesions. Results The lesions included 20 pancreatic masses (55 %), six gastric subepithelial lesions (17 %), five lymph nodes (14 %) and five other abdominal masses (14 %). Mean ± SD lesion size was 3.8 ±â€Š2.0 cm. The final diagnosis was malignant in 27 lesions (75 %) and benign in nine lesions (25 %). We found EUS-FNB procured significantly more median total tissue area (5.2 mm 2 vs. 1.9 mm 2 , P  < 0.001), diagnostic tissue area (2.2 mm 2 vs. 0.9 mm 2 , P  = 0.029), and DS area (2 mm 2 vs. 0.1 mm 2 , P  = 0.001) in lesions diagnosed as carcinoma (n = 23), as compared to EUS-FNA. In pancreatic lesions, EUS-FNB obtained significantly more nucleic acid than EUS-FNA (median; 4,085 ng vs. 2912 ng, P  = 0.02). There was no difference in the cellblock or rapid on-site cytological evaluation (ROSE) diagnostic yield between the needles. Conclusion The 22G EUS-FNB provides more histological core tissue and adequate nucleic acid yield compared to 22G EUS-FNA. In this study, the diagnostic performance was similar between the needles.

Type 1 and 2 diabetes mellitus: A review on current treatment approach and gene therapy as potential intervention.

Type 1 and type 2 diabetes mellitus is a serious and lifelong condition commonly characterised by abnormally elevated blood glucose levels due to a failure in insulin production or a decrease in insulin sensitivity and function. Over the years, prevalence of diabetes has increased globally and it is classified as one of the leading cause of high mortality and morbidity rate. Furthermore, diabetes confers a huge economic burden due to its management costs as well as its complications are skyrocketing. The conventional medications in diabetes treatment focusing on insulin secretion and insulin sensitisation cause unwanted side effects to patients and lead to incompliance as well as treatment failure. Besides insulin and oral hypoglycaemic agents, other treatments such as gene therapy and induced ß-cells regeneration have not been widely introduced to manage diabetes. Therefore, this review aims to deliver an overview of the current conventional medications in diabetes, discovery of newer pharmacological drugs and gene therapy as a potential intervention of diabetes in the future.

Early-life exposure to endocrine disrupting chemicals associates with childhood obesity

Increasing prevalence of childhood obesity poses threats to the global health burden. Because this rising prevalence cannot be fully explained by traditional risk factors such as unhealthy diet and physical inactivity, early-life exposure to endocrine disrupting chemicals (EDCs) is recognized as emerging novel risk factors for childhood obesity. EDCs can disrupt the hormone-mediated metabolic pathways, affect children’s growth and mediate the development of childhood obesity. Many organic pollutants are recently classified to be EDCs. In this review, we summarized the epidemiological and laboratory evidence related to EDCs and childhood obesity, and discussed the possible mechanisms underpinning childhood obesity and early-life exposure to non-persistent organic pollutants (phthalates, bisphenol A, triclosan) and persistent organic pollutants (dichlorodiphenyltrichloroethane, polychlorinated biphenyls, polybrominated diphenyl ethers, per- and polyfluoroalkyl substances). Understanding the relationship between EDCs and childhood obesity helps to raise public awareness and formulate public health policy to protect the youth from exposure to the harmful effects of EDCs.

Diverse Applications of Nanomedicine.

The design and use of materials in the nanoscale size range for addressing medical and health-related issues continues to receive increasing interest. Research in nanomedicine spans a multitude of areas, including drug delivery, vaccine development, antibacterial, diagnosis and imaging tools, wearable devices, implants, high-throughput screening platforms, etc. using biological, nonbiological, biomimetic, or hybrid materials. Many of these developments are starting to be translated into viable clinical products. Here, we provide an overview of recent developments in nanomedicine and highlight the current challenges and upcoming opportunities for the field and translation to the clinic.

Comparison of the sensitivity and specificity of p16/Ki-67 dual staining and HPV DNA testing of abnormal cervical cytology in the detection of histology proven cervical intraepithelial neoplasia grade 2 and above (CIN 2+)

Introduction: Human papillomavirus (HPV) testing is used as a means of triaging cervico-vaginalsmears with low grade squamous abnormalities or as part of co-testing with cytology. While HPVtesting has a high sensitivity, it has a low specificity in detecting cervical intraepithelial neoplasiagrade 2 and above (CIN 2+) leading to unnecessary colposcopy referrals. We investigate the accuracyof the p16/Ki-67 dual immunocytochemical stain in determining the presence of CIN 2+ lesions onhistology and its potential as a superior biomarker for triage. Methods: Liquid based cervico-vaginalcytology specimens with squamous abnormalities and corresponding histology from 97 women withsubsequent colposcopy and biopsy were included. The specimens were then subjected to the dual stainand Roche Cobas 4800 multiplex real time PCR HPV DNA testing. The sensitivity and specificity ofthe dual stain and HPV testing were calculated using CIN 2+ on histology as a reference standard.Results: The sensitivity and specificity of the dual stain in detecting histology proven CIN 2+ was93.7% and 76.5% while HPV testing was 85.7% and 14.7% respectively. Of the 44 women withASCUS or LSIL on cytology, the dual stain also reduced the number of unnecessary colposcopyreferrals from 27 to 7 when used as a triage marker compared to HPV testing. Conclusion: p16/Ki-67dual stain was more sensitive and specific than HPV testing in determining the presence of CIN 2+on histology. It could triage low grade cervico-vaginal specimens more effectively and potentiallyhelp women avoid unnecessary colposcopies. Future studies are needed to further evaluate its rolein cervical cancer screening programmes.

Bioactive molecules: current trends in discovery, synthesis, delivery and testing

Important bioactive molecules are molecules that are pharmacologically active derived from natural sources and through chemical synthesis. Over the years many of such molecules have been discovered through bioprospective endeavours. The discovery of taxol from the pacific yew tree bark that has the ability in stabilising cellular microtubules represents one of the hallmarks of success of such endeavours. In recent years, the discovery process has been aided by the rapid development of techniques and technologies in chemistry and biotechnology. The progress in advanced genetics and computational biology has also transformed the way hypotheses are formulated as well as the strategies for drug discovery. Of equal importance is the use of advanced drug delivery vehicles in enhancing the efficacy and bioavailability of bioactive molecules. The availability of suitable animal models for testing and validation is yet another major determinant in increasing the prospect for clinical trials of bioactive molecules.

Obstructive sleep apnoea in Singapore: polysomnography data from a tertiary sleep disorders unit

<p><b>INTRODUCTION</b>Comprehensive sleep architecture and respiratory event data in local patients with suspected obstructive sleep apnoea (OSA) from overnight polysomnography (PSG), the gold standard for the evaluation of sleep-related breathing disorders, are not widely available. We present 1 year retrospective PSG data with the objective of describing PSG characteristics of patients evaluated for OSA in Singapore.</p><p><b>MATERIALS AND METHODS</b>PSG data of patients evaluated for OSA in 1 year (January through December 2005) in the Sleep Laboratory of a public tertiary hospital were retrospectively reviewed.</p><p><b>RESULTS</b>Five hundred and eighty-four diagnostic PSG studies were performed in patients with symptoms suggestive of sleep-disordered breathing, including snoring, excessive daytime sleepiness, unrefreshing sleep, or recurrent unexplained awakenings. There were 449 male patients (76.9%) and 135 female patients (23.1%), with a mean age of 47.5 years (SD 12.7). Men were on average younger than women, 46.1 years versus 52.0 years (P <0.0005). The mean body mass index (BMI) was 27.9 (SD 6.7), with no significant difference between genders. An association was shown between apnoea-hypopnoea index (AHI) and BMI (Pearson correlation index r = 0.362). Men had overall significantly higher AHI (16.5 vs 9), shorter mean sleep onset latency (11 vs 16.5 minutes), more light sleep (65.5% vs 58.9%), less deep sleep (17.7% vs 23%), and more respiratory event related arousals per hour of sleep (11.6 vs 5.1) (P <0.0005). Severity was classified: AHI <5 ("Normal Overall AHI") (28.3%), AHI 5-15 ("Mild") (22.3%), AHI >15-30 ("Moderate") (18.3%), AHI >30 ("Severe") (31.2%). There was no significant age difference among the 4 groups. More severe OSA patients were significantly heavier, and had more light sleep, less deep sleep, less REM sleep, more respiratory event related arousals and lower levels of oxygen desaturation.</p><p><b>CONCLUSION</b>OSA is predominant in middle-aged, overweight Singapore males and much less common in females who tend to be older. A majority of patients have moderate to severe OSA, which significantly disturbs normal sleep architecture. The relatively lower BMI compared to Caucasian OSA populations may be related to local craniofacial characteristics and/or higher percentage of body fat for BMI which has been described in Singaporeans.</p>

An unusual case of episodic stupor.

We present a case of episodic stupor associated with a myriad of neuropyschiatric manifestations that baffled doctors until they were recognized as sleep attacks. Continuous monitoring and recognition of a cyclical pattern of symptoms and signs helped to uncover the underlying cause of a rapidly cycling bipolar disorder. The symptoms abated quickly and persistently when treated by olanzapine and lithium.