Weight bias and stigma in healthcare professionals: a narrative review with a Singapore lens.

Addressing weight stigma is essential to obesity management as it causes inequalities in healthcare and impacts the outcomes of health. This narrative review summarises systematic review findings about the presence of weight bias in healthcare professionals, and interventions to reduce weight bias or stigma in these professionals. Two databases (PubMed and Cumulative Index to Nursing and Allied Health Literature [CINAHL]) were searched. Seven eligible reviews were identified from 872 search results. Four reviews identified the presence of weight bias, and three investigated trials to reduce weight bias or stigma in healthcare professionals. The findings may help further research and the treatment, health and well-being of individuals with overweight or obesity in Singapore. Weight bias was prevalent among qualified and student healthcare professionals globally, and there is a lack of clear guidance for effective interventions to reduce it, particularly in Asia. Future research is essential to identify the issues and inform initiatives to reduce weight bias and stigma among healthcare professionals in Singapore.

SARS-CoV-2 mRNA Vaccination and Graves' Disease: A Report of 12 Cases and Review of the Literature.

CONTEXT AND OBJECTIVE: Thyroid autoimmunity has been reported to be associated with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and the SARS-CoV-2 vaccination recently. We report a series of patients who presented with new onset or relapse of Graves' disease-related hyperthyroidism shortly after receiving the SARS-CoV-2 messenger RNA (mRNA) vaccine at a single tertiary institution in Singapore. METHODS AND RESULTS: We describe 12 patients who developed hyperthyroidism within a relatively short interval (median onset, 17 [range, 5-63] days) after receiving the SARS-CoV-2 mRNA vaccine. The majority were females (11/12) with median age of 35.5 (range, 22-74) years. Six patients had new-onset hyperthyroidism, whereas the other 6 had relapse of previously well-controlled Graves' disease. TSH receptor antibody concentrations ranged from 2.4 to 32 IU/L. The majority of the patients were able to go for the second dose of the vaccine without any further exacerbations. Literature review revealed 21 other similar cases reported from across the world. CONCLUSION: Our case series provides insight into the characteristics of individuals in whom Graves' disease was triggered by the SARS-CoV-2 vaccination. Clinicians need to be vigilant of precipitation or exacerbation of autoimmune thyroid disorders in predisposed individuals after exposure to the SARS-CoV-2 vaccination. Further epidemiological and mechanistic studies are required to elucidate the possible associations between the SARS-CoV-2 vaccines and the development of thyroid autoimmunity.

A 15-year pheochromocytoma and paraganglioma experience in a single centre: a Singapore perspective.

Introduction: Pheochromocytomas (PCC) and paragangliomas (PGL) are rare endocrine tumours. The objective of this study was to describe our experience with these two entities in a Singapore population. Methods: We identified patients with positive histopathological confirmations of PCC and PGL who were treated at a tertiary Singapore hospital between January 2000 and December 2015. The results were analysed for clinical presentations, treatment and long-term outcomes. Results: A total of 27 cases (20 PCC, 7 PGL) were identified over a 15-year period. One case of PGL developed bilateral disease on follow-up. There were 17 male and 10 female patients with a median age of 57 (range 24-77) years. A positive family history was uncommon and present in only 3.7% of patients. Uniquely, the top three presenting symptoms were abdominal discomfort, palpitations and diaphoresis. Despite adequate preoperative preparation, intraoperative haemodynamic instability occurred in 70.4% and early postoperative hypotension occurred in 11.1% of patients. After surgery, hypertension was resolved in 41.2% (7/17) and diabetes mellitus in 60% (3/5). Disease recurrence was reported in 22.2% and distant metastases in 14.8%. At the end of the follow-up period (median 35 [range 3-148] months), 70.4% were still alive. Conclusion: PCC and PGL can present with a wide range of symptoms. Intraoperative haemodynamic instability was frequent despite good preoperative preparation. Disease recurrences and metastasis occurred in up to one-fifth of the patients. Genetic screening should be offered to patients with PCC and PGL.

Metabolic effects of brown fat in transitioning from hyperthyroidism to euthyroidism.

OBJECTIVE: Brown adipose tissue (BAT) controls metabolic rate through thermogenesis. As its regulatory factors during the transition from hyperthyroidism to euthyroidism are not well established, our study investigated the relationships between supraclavicular brown adipose tissue (sBAT) activity and physiological/metabolic changes with changes in thyroid status. DESIGN: Participants with newly diagnosed Graves' disease were recruited. A thionamide antithyroid drug (ATD) such as carbimazole (CMZ) or thiamazole (TMZ) was prescribed in every case. All underwent energy expenditure (EE) measurement and supraclavicular infrared thermography (IRT) within a chamber calorimeter, as well as 18F-fluorodeoxyglucose (18F-FDG) positron-emission tomography/magnetic resonance (PET/MR) imaging scanning, with clinical and biochemical parameters measured during hyperthyroidism and repeated in early euthyroidism. PET sBAT mean/maximum standardized uptake value (SUV mean/max), MR supraclavicular fat fraction (sFF) and mean temperature (Tscv) quantified sBAT activity. RESULTS: Twenty-one (16 female/5 male) participants aged 39.5 ± 2.5 years completed the study. The average duration to attain euthyroidism was 28.6 ± 2.3 weeks. Eight participants were BAT-positive while 13 were BAT-negative. sFF increased with euthyroidism (72.3 ± 1.4% to 76.8 ± 1.4%; P < 0.01), but no changes were observed in PET SUV mean and Tscv. Significant changes in serum-free triiodothyronine (FT3) levels were related to BAT status (interaction P value = 0.04). FT3 concentration at hyperthyroid state was positively associated with sBAT PET SUV mean (r = 0.58, P = 0.01) and resting metabolic rate (RMR) (P < 0.01). CONCLUSION: Hyperthyroidism does not consistently lead to a detectable increase in BAT activity. FT3 reduction during the transition to euthyroidism correlated with BAT activity.

Loss of CPAP in developing mouse brain and its functional implication for human primary microcephaly.

Primary microcephaly (MCPH) is a neurodevelopmental disorder characterized by small brain size with mental retardation. CPAP (also known as CENPJ), a known microcephaly-associated gene, plays a key role in centriole biogenesis. Here, we generated a previously unreported conditional knockout allele in the mouse Cpap gene. Our results showed that conditional Cpap deletion in the central nervous system preferentially induces formation of monopolar spindles in radial glia progenitors (RGPs) at around embryonic day 14.5 and causes robust apoptosis that severely disrupts embryonic brains. Interestingly, microcephalic brains with reduced apoptosis are detected in conditional Cpap gene-deleted mice that lose only one allele of p53 (also known as Trp53), while simultaneous removal of p53 and Cpap rescues RGP death. Furthermore, Cpap deletion leads to cilia loss, RGP mislocalization, junctional integrity disruption, massive heterotopia and severe cerebellar hypoplasia. Together, these findings indicate that complete CPAP loss leads to severe and complex phenotypes in developing mouse brain, and provide new insights into the causes of MCPH.

Agoitrous Graves' Hyperthyroidism with Markedly Elevated Thyroid Stimulating Immunoglobulin Titre displaying Rapid Response to Carbimazole with Discordant Thyroid Function.

We characterize the clinical and laboratory characteristics of 5 patients with Graves' thyrotoxicosis whose serum free thyroxine (fT4) concentration decreased unexpectedly to low levels on conventional doses of carbimazole (CMZ) therapy. The initial fT4 mean was 40.0 pM, range 25-69 pM. Thyroid volume by ultrasound measured as mean 11 ml, range 9.0-15.6 ml. Initial TSI levels measured 1487% to >4444%. Serum fT4 fell to low-normal or hypothyroid levels within 3.6 to 9.3 weeks of initiating CMZ 5 to 15 mg daily, and subsequently modulated by fine dosage adjustments. In one patient, serum fT4 fluctuated in a "yo-yo" pattern. There also emerged a pattern of low normal/low serum fT4 levels associated with discordant low/mid normal serum TSH levels respectively, at normal serum fT3 levels. The long-term daily-averaged CMZ maintenance dose ranged from 0.7 mg to 3.2 mg. Patients with newly diagnosed Graves' hyperthyroidism who have small thyroid glands and markedly elevated TSI titres appear to be "ATD dose sensitive." Their TFT on ATD therapy may display a "central hypothyroid" pattern. We suggest finer CMZ dose titration at closer follow-up intervals to achieve biochemical euthyroidism.

Patient with multiple acyl-CoA dehydrogenase deficiency disease and ETFDH mutations benefits from riboflavin therapy: a case report.

BACKGROUND: Lipid storage myopathy (LSM) is a diverse group of lipid metabolic disorders with great variations in the clinical phenotype and age of onset. Classical multiple acyl-CoA dehydrogenase deficiency (MADD) is known to occur secondary to mutations in electron transfer flavoprotein dehydrogenase (ETFDH) gene. Whole exome sequencing (WES) with clinical correlations can be useful in identifying genomic alterations for targeted therapy. CASE PRESENTATION: We report a patient presented with severe muscle weakness and exercise intolerance, suggestive of LSM. Diagnostic testing demonstrated lipid accumulation in muscle fibres and elevated plasma acyl carnitine levels. Exome sequencing of the proband and two of his unaffected siblings revealed compound heterozygous mutations, c.250G > A (p.Ala84Thr) and c.770A > G (p.Tyr257Cys) in the ETFDH gene as the probable causative mutations. In addition, a previously unreported variant c.1042C > T (p.Arg348Trp) in ACOT11 gene was found. This missense variant was predicted to be deleterious but its association with lipid storage in muscle is unclear. The diagnosis of MADD was established and the patient was treated with riboflavin which resulted in rapid clinical and biochemical improvement. CONCLUSIONS: Our findings support the role of WES as an effective tool in the diagnosis of highly heterogeneous disease and this has important implications in the therapeutic strategy of LSM treatment.

Giant phaeochromocytoma presenting with an acute stroke: reappraising phaeochromocytoma surveillance for the neurofibromatosis type 1 phakomatosis.

Neurofibromatosis type 1 (NF1) is a multisystem genetic disorder associated with reduced lifespan attributed largely to malignancy and vascular causes. One of the tumours associated with NF1 is phaeochromocytoma. The phaeochromocytoma has earned the moniker, a 'great mimicker', due to its varied means of presentation. We present a patient with NF1 who was diagnosed with a giant 20 cm phaeochromocytoma after suffering from an ischaemic stroke. Current guidelines do not advocate surveillance of phaeochromocytoma in asymptomatic patients with NF1, unlike other genetic syndromes associated with phaeochromocytoma. However, there is increasing evidence that this approach may not help in the early detection and treatment of this potentially life-threatening disease. Our patient remained hypertensive after surgery despite achieving biochemical cure. The suggested chronicity of the underlying tumour in our patient is a reminder to practising clinicians to rethink our strategy in identifying phaeochromocytoma in adults with NF1.

Pulsed DC Electric Field-Induced Differentiation of Cortical Neural Precursor Cells.

We report the differentiation of neural stem and progenitor cells solely induced by direct current (DC) pulses stimulation. Neural stem and progenitor cells in the adult mammalian brain are promising candidates for the development of therapeutic neuroregeneration strategies. The differentiation of neural stem and progenitor cells depends on various in vivo environmental factors, such as nerve growth factor and endogenous EF. In this study, we demonstrated that the morphologic and phenotypic changes of mouse neural stem and progenitor cells (mNPCs) could be induced solely by exposure to square-wave DC pulses (magnitude 300 mV/mm at frequency of 100-Hz). The DC pulse stimulation was conducted for 48 h, and the morphologic changes of mNPCs were monitored continuously. The length of primary processes and the amount of branching significantly increased after stimulation by DC pulses for 48 h. After DC pulse treatment, the mNPCs differentiated into neurons, astrocytes, and oligodendrocytes simultaneously in stem cell maintenance medium. Our results suggest that simple DC pulse treatment could control the fate of NPCs. With further studies, DC pulses may be applied to manipulate NPC differentiation and may be used for the development of therapeutic strategies that employ NPCs to treat nervous system disorders.