Access to COVID-19 vaccination by socio-economic status in older Singaporean adults: a population-based cohort study.

OBJECTIVES: Socio-economic status (SES) disparities exist in the uptake of COVID-19 vaccination; however, most studies were conducted during the initial pandemic wave when vaccination was less discretionary, limiting generalizability. We aimed to determine whether differences in vaccination uptake across SES strata widened after the removal of vaccination-differentiated measures prior to the rollout of the second boosters, in a nationwide cohort of older Singaporeans at higher risk of severe-COVID-19. STUDY DESIGN: Retrospective population-based cohort study. METHODS: Retrospective population-based cohort study of all Singaporeans aged ≥60 years from 22nd February 2021-14th February 2023. Cox regression models controlling for demographics and comorbidities were used to estimate hazard-ratios (HRs) for the uptake of primary vaccination as well as first/second boosters, as recorded in the national vaccination registry, according to SES (housing type). RESULTS: 836,170 individuals were included for completion of a primary vaccine series; 784,938 individuals for completion of the first booster and 734,206 individuals for the completion of the second booster. Differences in vaccination uptake by SES strata were observed (e.g. vaccination uptake in lowest-SES [1-2 room public-housing] versus highest-SES [private housing]: second booster, 47.6% vs. 58.1%; first booster, 93.9% vs. 98.0%). However, relative differences did not markedly widen during second booster rollout when vaccination was more discretionary (e.g. amongst those aged 60-69 years: 0.75 [95% CI = 0.73-0.76] for the first booster; 0.81 [95% CI = 0.79-0.84] for the second booster). CONCLUSION: While differences in vaccination uptake across SES strata by housing type persisted during the rollout of primary vaccination and subsequent boosters in a nationwide cohort of older Singaporeans, differences did not widen substantially when vaccination was made more discretionary.

Management of patent foramen ovale in embolic stroke of undetermined source patients: Malaysian experts' consensus.

INTRODUCTION: About 20 to 40% of ischaemic stroke causes are cryptogenic. Embolic stroke of undetermined source (ESUS) is a subtype of cryptogenic stroke which is diagnosed based on specific criteria. Even though patent foramen ovale (PFO) is linked with the risk of stroke, it is found in about 25% of the general population, so it might be an innocent bystander. The best way to treat ESUS patients with PFO is still up for discussion. MATERIALS AND METHODS: Therefore, based on current evidence and expert opinion, Malaysian expert panels from various disciplines have gathered to discuss the management of ESUS patients with PFO. This consensus sought to educate Malaysian healthcare professionals to diagnose and manage PFO in ESUS patients based on local resources and facilities. RESULTS: Based on consensus, the Malaysian expert recommended PFO closure for embolic stroke patients who were younger than 60, had high RoPE scores and did not require long-term anticoagulation. However, the decision should be made after other mechanisms of stroke have been ruled out via thorough investigation and multidisciplinary evaluation. The PFO screening should be made using readily available imaging modalities, ideally contrasttransthoracic echocardiogram (c-TTE) or contrasttranscranial Doppler (c-TCD). The contrast-transesophageal echocardiogram (c-TEE) should be used for the confirmation of PFO diagnosis. The experts advised closing PFO as early as possible because there is limited evidence for late closure. For the post-closure follow-up management, dual antiplatelet therapy (DAPT) for one to three months, followed by single antiplatelet therapy (APT) for six months, is advised. Nonetheless, with joint care from a cardiologist and a neurologist, the multidisciplinary team will decide on the continuation of therapy.

Detection and molecular characterization of infectious spleen and kidney necrosis virus from major ornamental fish breeding states in Peninsular Malaysia.

'Gold standard' OIE reference PCR assay was utilized to detect the presence of infectious spleen and kidney necrosis virus (ISKNV) in freshwater ornamental fish from Malaysia. From total of 210 ornamental fish samples representing 14 species, ISKNV was detected in 36 samples representing 5 fish species. All positive cases did not show any clinical signs of ISKNV. Three restriction enzymes analyses showed that the fish were infected by identical strains of the same virus species within Megalocytivirus genus. Major capsid protein (MCP) genes of 10 ISKNV strains were sequenced and compared with 9 other reference nucleotide sequences acquired from GenBank. Sequence analysis of MCP gene showed that all strains detected in this study were closely related to the reference ISKNV with nucleotide sequence identity that was ranging from 99.8% to 100%. In addition, phylogenetic analysis of MCP gene revealed that viruses from genus Megalocytivirus can be divided into three genotypes: genotype 1 include reference ISKNV and all other strains that were detected in this study, genotype 2 include viruses closely related to red sea bream iridovirus (RSIV), and genotype 3 include viruses closely related turbot reddish body iridovirus (TRBIV).

Oxidised cellulose in musculoskeletal oncology procedure: Does it reduce postoperative blood loss?

BACKGROUND: Major musculoskeletal oncology procedures often result in perioperative bleeding. This exposes patients to allogeneic red blood cell transfusion and its potential complications, thus increasing the risk of surgical wound infection and prolonged hospital stay. This study aimed to investigate the efficacy of oxidised cellulose, a topical haemostatic agent, in reducing postoperative blood loss and its subsequent risks. METHODS: In this randomised controlled trial, 40 patients undergoing major musculoskeletal oncology procedures were assigned to control and intervention groups. Oxidised cellulose was inserted into the surgical wound after the resection's conclusion before the wound's closure to reduce postoperative bleeding for patients in the intervention group. Postoperative closed suction drain system (Redivac TM) volume, drop in haemoglobin level, allogeneic red blood cell transfusion rate, duration of surgery, and length of hospital stay were compared between the two groups. RESULTS: The postoperative Redivac volume (Control: 432 MLS vs. Intervention: 431.75 MLS), drop in haemoglobin level (Control: 3.12 g/dL vs. Intervention: 3.06 g/dL), duration of surgery (Control: 134 vs. Intervention: 156 min), and allogeneic red blood cell transfusion were lower in the intervention group (Control: 204 MLS vs. Intervention: 170 MLS), but they were not statistically significant (p > 0.05) (Control: 134 vs. Intervention: 156 min). Mean hospital stay was similar in both groups (Control: 5.45 days vs. Intervention: 5.85 days). CONCLUSION: Oxidised cellulose use does not significantly affect postoperative blood loss, the rate of allogeneic blood transfusion, and hospital stay. However, we believe its use contributes positively but not considerably towards lower postoperative blood loss in musculoskeletal oncology surgeries.

Tuberculosis in captive Asian elephants (Elephas maximus) in Peninsular Malaysia.

A cross-sectional study was conducted from 10 January to 9 April 2012, to determine the seroprevalence of tuberculosis (TB) of all captive Asian elephants and their handlers in six locations in Peninsular Malaysia. In addition, trunk-wash samples were examined for tubercle bacillus by culture and polymerase chain reaction (PCR). For 63 elephants and 149 elephant handlers, TB seroprevalence was estimated at 20.4% and 24.8%, respectively. From 151 trunkwash samples, 24 acid-fast isolates were obtained, 23 of which were identified by hsp65-based sequencing as non-tuberculous mycobacteria. The Mycobacterium tuberculosis-specific PCR was positive in the trunk-wash samples from three elephants which were also seropositive. Conversely, the trunk wash from seven seropositive elephants were PCR negative. Hence, there was evidence of active and latent TB in the elephants and the high seroprevalence in the elephants and their handlers suggests frequent, close contact, two-way transmission between animals and humans within confined workplaces.

Anomalous Ferromagnetism of quasiparticle doped holes in cuprate heterostructures revealed using resonant soft X-ray magnetic scattering.

We report strong ferromagnetism of quasiparticle doped holes both within the ab-plane and along the c-axis of Cu-O planes in low-dimensional Au/d-La1.8Ba0.2CuO4/LaAlO3(001) heterostructures (d = 4, 8 and 12 unit-cells) using resonant soft X-ray and magnetic scattering together with X-ray magnetic circular dichroism. Interestingly, ferromagnetism is stronger at a hole doped peak and at an upper Hubbard band of O with spin-polarization degree as high as 40%, revealing strong ferromagnetism of Mottness. For in-ab-plane spin-polarizations, the spin of doped holes in O2p-Cu3d-O2p is a triplet state yielding strong ferromagnetism. For out-of-ab-plane spin-polarization, while the spins of doped holes in both O2p-O2p and Cu3d-Cu3d are triplet states, the spin of doped holes in Cu3d-O2p is a singlet state yielding ferrimagnetism. A ferromagnetic-(002) Bragg-peak of the doped holes is observed and enhanced as a function of d revealing strong ferromagnetism coupling between Cu-O layers along the c-axis.

Substrate effects on surface morphologies and magnetic properties of nanostructured FePt thin films.

The substrate effects on surface morphologies, crystal structures, and magnetic properties of the sputter-deposited FePt thin films on Corning 1737, normal glass, and Si wafer substrates, respectively, were investigated. High in-plane coercivities of 10 kOe were obtained for the air-annealed films on Corning 1737 and Si wafer, where both films similarly have granular-like morphologies. Besides, increasing grain size and surface roughness of all the FePt films with the post-anneal temperature were observed. Moreover, partially separated grains were seen in the film on Si wafer, where the formation of Fe silicides during post-anneal is suspected, in which has enhanced the magnetic ordering.

2,4-Dinitrophenol overdose - Everything old is new again.

A complete case example of a fatal 2,4-dinitrophenol (DNP) overdose involving a 23-year-old male is described. Included are details of not only the patient's presentation symptoms and treatment, but also the subsequent findings of the coronial investigation process including the autopsy, post-mortem computed tomography (PMCT) scanning and toxicological analysis and results. The patient presented with elevated temperature, heart rate and blood pressure. Multiple treatments were conducted to counteract these symptoms, however the patient died approximately 1.5 hours after hospital admission and some 4.5 hours after the DNP was initially consumed. Autopsy revealed the presence of cardiovascular disease that was contributory to death and post-mortem computed tomography showed evidence of decompositional intravascular gas in the neck, head, face, lower abdomen, heart and hepatic systems. Toxicological analysis was completed by protein precipitation with methanol and subsequent instrumental analysis by LC/MS/MS in negative ion mode. The antemortem blood specimen showed the presence of tadalafil, two anabolic steroids and a DNP concentration of 110 mg/kg which is consistent with other reported DNP fatalities. Despite the small amount of time between the antemortem specimen collection and death, the DNP concentration identified in the femoral blood post-mortem specimen was comparably low (5.5 mg/kg). DNP concentrations also reduced during an extended period of specimen storage prior to analysis indicating some instability in biological specimens even when refrigerated or frozen. DNP was found to be distributed primarily in the aqueous tissues (blood, vitreous, bile) rather than solid matrices (liver, kidney, muscle).

Human Hendra virus infection causes acute and relapsing encephalitis.

AIM: To study the pathology of two cases of human Hendra virus infection, one with no clinical encephalitis and one with relapsing encephalitis. METHODS: Autopsy tissues were investigated by light microscopy, immunohistochemistry and in situ hybridization. RESULTS: In the patient with acute pulmonary syndrome but not clinical acute encephalitis, vasculitis was found in the brain, lung, heart and kidney. Occasionally, viral antigens were demonstrated in vascular walls but multinucleated endothelial syncytia were absent. In the lung, there was severe inflammation, necrosis and viral antigens in type II pneumocytes and macrophages. The rare kidney glomerulus showed inflammation and viral antigens in capillary walls and podocytes. Discrete necrotic/vacuolar plaques in the brain parenchyma were associated with antigens and viral RNA. Brain inflammation was mild although CD68(+) microglia/macrophages were significantly increased. Cytoplasmic viral inclusions and antigens and viral RNA in neurones and ependyma suggested viral replication. In the case of relapsing encephalitis, there was severe widespread meningoencephalitis characterized by neuronal loss, macrophages and other inflammatory cells, reactive blood vessels and perivascular cuffing. Antigens and viral RNA were mainly found in neurones. Vasculitis was absent in all the tissues examined. CONCLUSIONS: The case of acute Hendra virus infection demonstrated evidence of systemic infection and acute encephalitis. The case of relapsing Hendra virus encephalitis showed no signs of extraneural infection but in the brain, extensive inflammation and infected neurones were observed. Hendra virus can cause acute and relapsing encephalitis and the findings suggest that the pathology and pathogenesis are similar to Nipah virus infection.

Early intervention for mild cognitive impairment: a randomised controlled trial.

BACKGROUND: Positive effects are reported for memory training for healthy older adults, and yet there is limited information about the benefit of cognitive intervention for older adults with increasing memory difficulties-mild cognitive impairment. OBJECTIVE: To investigate the usefulness of an early cognitive intervention for the memory difficulties experienced by people with amnestic mild cognitive impairment. METHODS: Using a randomised control design, 52 participants with amnestic mild cognitive impairment and their family partners were randomly assigned to a cognitive intervention (memory rehabilitation group) or waitlist (control group). Participants were assessed on primary measures of everyday memory (prospective memory) and memory strategies at 2 weeks' and 4 months' follow-up; secondary measures of contentment with memory and the family participants' knowledge of memory strategies were also assessed. RESULTS: Everyday memory, measured by performance on prospective memory tasks, significantly improved following intervention, although self-appraisal of everyday memory did not demonstrate a similar intervention effect. Knowledge and use of memory strategies also significantly increased following intervention. Furthermore, family knowledge of memory strategies increased following intervention. There was a strong trend towards improvement in contentment with memory immediately following intervention, but this effect was not significant. CONCLUSIONS: Early intervention for memory difficulties in amnestic mild cognitive impairment, using cognitive rehabilitation in compensatory strategies, can assist in minimising everyday memory failures as evaluated by performance on prospective memory tasks and knowledge of memory strategies.

LAD-1, the Caenorhabditis elegans L1CAM homologue, participates in embryonic and gonadal morphogenesis and is a substrate for fibroblast growth factor receptor pathway-dependent phosphotyrosine-based signaling.

This study shows that L1-like adhesion (LAD-1), the sole Caenorhabditis elegans homologue of the L1 family of neuronal adhesion molecules, is required for proper development of the germline and the early embryo and embryonic and gonadal morphogenesis. In addition, the ubiquitously expressed LAD-1, which binds to ankyrin-G, colocalizes with the C. elegans ankyrin, UNC-44, in multiple tissues at sites of cell-cell contact. Finally, we show that LAD-1 is phosphorylated in a fibroblast growth factor receptor (FGFR) pathway-dependent manner on a tyrosine residue in the highly conserved ankyrin-binding motif, FIGQY, which was shown previously to abolish the L1 family of cell adhesion molecule (L1CAM) binding to ankyrin in cultured cells. Immunofluorescence studies revealed that FIGQY-tyrosine-phosphorylated LAD-1 does not colocalize with nonphosphorylated LAD-1 or UNC-44 ankyrin but instead is localized to sites that undergo mechanical stress in polarized epithelia and axon-body wall muscle junctions. These findings suggest a novel ankyrin-independent role for LAD-1 related to FGFR signaling. Taken together, these results indicate that L1CAMs constitute a family of ubiquitous adhesion molecules, which participate in tissue morphogenesis and maintaining tissue integrity in metazoans.

Neuropsychiatric lupus and reversible posterior leucoencephalopathy syndrome: a challenging clinical dilemma.

Reversible posterior leucoencephalopathy syndrome (RPLS) has been increasingly recognized and reported in the literature. While the condition has been well described in patients with acute hypertension, pre-eclampsia, eclampsia, post-transplantation and chemotherapy, RPLS has been increasingly identified in patients with autoimmune diseases such as systemic lupus erythematosus (SLE). Though experience in the diagnosis and management of RPLS in patients with SLE is likely accumulating, few have systematically worked out the strategy to distinguish RPLS from neuropsychiatric SLE (NPSLE) and lupus-related complications of the central nervous system (CNS). Prompt recognition of, and differentiation between, these conditions is essential since their clinical presentations substantially overlap and yet their management strategy and subsequent outcomes can be entirely different. Indeed, inappropriate treatment such as augmentation of immunosuppression may be detrimental to patients with RPLS. A high index of suspicion of RPLS, prompt magnetic resonance imaging of the brain, including diffusion imaging, exclusion of CNS infection and metabolic derangement, a comprehensive medication review accompanied by timely and aggressive control of blood pressure and seizure are keys to successful management of RPLS. Such treatment strategy ensures a very high chance of total neurological recovery in lupus patients with RPLS.

Preoperative Red Cell Distribution Width and 30-day mortality in older patients undergoing non-cardiac surgery: a retrospective cohort observational study.

Increased red cell distribution width (RDW) is associated with poorer outcomes in various patient populations. We investigated the association between preoperative RDW and anaemia on 30-day postoperative mortality among elderly patients undergoing non-cardiac surgery. Medical records of 24,579 patients aged 65 and older who underwent surgery under anaesthesia between 1 January 2012 and 31 October 2016 were retrospectively analysed. Patients who died within 30 days had higher median RDW (15.0%) than those who were alive (13.4%). Based on multivariate logistic regression, in our cohort of elderly patients undergoing non-cardiac surgery, moderate/severe preoperative anaemia (aOR 1.61, p = 0.04) and high preoperative RDW levels in the 3rd quartile (>13.4% and ≤14.3%) and 4th quartile (>14.3%) were significantly associated with increased odds of 30-day mortality - (aOR 2.12, p = 0.02) and (aOR 2.85, p = 0.001) respectively, after adjusting for the effects of transfusion, surgical severity, priority of surgery, and comorbidities. Patients with high RDW, defined as >15.7% (90th centile), and preoperative anaemia have higher odds of 30-day mortality compared to patients with anaemia and normal RDW. Thus, preoperative RDW independently increases risk of 30-day postoperative mortality, and future risk stratification strategies should include RDW as a factor.

Feline bartonellosis associated with some clinicopathological conditions in a veterinary hospital in Selangor, Malaysia.

A cross-sectional study was conducted to determine the prevalence of feline bartonellosis and the associated clinicopathological findings in cats presented to the University Veterinary Hospital, Selangor, Malaysia from 2013-2014. Out of 284 cats examined, Bartonella DNA was detected in 48 (16.9%) cats using a specific polymerase chain reaction (PCR) assay targeting the internal transcribed spacer of Bartonella species. Bartonella henselae strain Houston was identified through BLAST analyses of randomly selected amplicons. Univariable analysis showed significant association of feline bartonellosis with cats < 2 years of age (OR 1.37, 95% CI 0.982-1.927, p = 0.036) and those presenting with ocular discharge (OR 3.211, 95% CI 1.422-7.248, p = 0.003). Significant associations of neutrophilia (OR 2.244, 95% CI 1.131-4.452, p = 0.019) and monocytosis (OR 2.476, 95% CI 1.154-5.312, p = 0.017) with bartonella infection in cats were observed. This study reports for the first time the prevalence (approximately 17%) of feline bartonellosis in Malaysia and highlights several clinicopathological factors associated with the disease.

Molecular Detection of Coxiella burnetii from Farm Animals and Ticks in Malaysia.

Coxiella burnetii, the causative agent of Q fever, is an intracellular bacterium of medical and veterinary importance. The reservoirs of C. burnetii are extensive which include mammals and arthropods, particularly ticks. As the organism is difficult to culture, this study was aimed to detect C. burnetii DNA in animal (mainly blood and vaginal samples of cattle, goats and sheep) and tick samples obtained from farm animals, wild rodents and vegetation. Two polymerase chain reaction (PCR) assays targeting IS1111 transposon-like gene (TransPCR) and com1 gene (OMP-PCR) were used for C. burnetii detection. Sequence determination of the amplified fragments and a real-time PCR assay were used to confirm PCR findings. C. burnetii DNA was detected from 9.1% of cattle blood and 4.2% vaginal samples, respectively. A small percentage (5.8%) of ticks (including Amblyomma, Dermacentor, Rhipicephalus and Haemaphysalis spp.) haboring C. burnetii were identified in this study. This study provides molecular evidence on the presence of C. burnetii in cattle and ticks. The possible zoonotic transmission of C. burnetii is yet to be investigated.

A structural rearrangement in the sodium channel pore linked to slow inactivation and use dependence.

Voltage-gated sodium (Na(+)) channels are a fundamental target for modulating excitability in neuronal and muscle cells. When depolarized, Na(+) channels may gradually enter long-lived, slow-inactivated conformational states, causing a cumulative loss of function. Although the structural motifs that underlie transient, depolarization-induced Na(+) channel conformational states are increasingly recognized, the conformational changes responsible for more sustained forms of inactivation are unresolved. Recent studies have shown that slow inactivation components exhibiting a range of kinetic behavior (from tens of milliseconds to seconds) are modified by mutations in the outer pore P-segments. We examined the state-dependent accessibility of an engineered cysteine in the domain III, P-segment (F1236C; rat skeletal muscle) to methanethiosulfonate-ethylammonium (MTSEA) using whole-cell current recordings in HEK 293 cells. F1236C was reactive with MTSEA applied from outside, but not inside the cell, and modification was markedly increased by depolarization. Depolarized F1236C channels exhibited both intermediate (I(M); tau approximately 30 ms) and slower (I(S); tau approximately 2 s) kinetic components of slow inactivation. Trains of brief, 5-ms depolarizations, which did not induce slow inactivation, produced more rapid modification than did longer (100 ms or 6 s) pulse widths, suggesting both the I(M) and I(S) kinetic components inhibit depolarization-induced MTSEA accessibility of the cysteine side chain. Lidocaine inhibited the depolarization-dependent sulfhydryl modification induced by sustained (100 ms) depolarizations, but not by brief (5 ms) depolarizations. We conclude that competing forces influence the depolarization-dependent modification of the cysteine side chain: conformational changes associated with brief periods of depolarization enhance accessibility, whereas slow inactivation tends to inhibit the side chain accessibility. The findings suggest that slow Na(+) channel inactivation and use-dependent lidocaine action are linked to a structural rearrangement in the outer pore.

One hundred years of the teaching of medicine in Singapore.

The Medical School was founded in 1905 in response to the need to train doctors for Singapore. In 2005, this School, now the Faculty of Medicine in the National University of Singapore, will celebrate her 100th year. This brief review attempts to chronicle the way in which the medical course has been designed over the years to address the principal aims of undergraduate medical education. From the inception of the Straits and Federated Malay States Government Medical School to the present, strong clinically based teaching was the key element, although there was some distinction between the foundational preclinical years and the clinical phases of training. Initially, this was necessitated by the fact that students were too poorly equipped in the sciences to have a more integrated curriculum. Over time, the structure of the course, learning objectives and teaching pedagogy and techniques became better developed. Of late, many of these elements have been revised and better articulated by the Faculty following a review. The method, frequency and emphasis of student evaluations have also changed as medical knowledge grows and the population becomes developed, with attendant disease pattern changes. The clinical relevance of the course and the need to train competent doctors remain the main mission of the Faculty of Medicine even in this age of molecular medicine and a technology-enhanced practice setting. Competency alone is, however, incomplete without good role models in the art of the practice of medicine. It is heartening to note that medical ethics and communications skills continue to be emphasised in the modern curriculum.

Adult-onset re-emergent stuttering as a presentation of Parkinson's disease.

INTRODUCTION: The basal ganglia-thalamocortical motor circuits are postulated to play a key role in the aetiopathogenesis of stuttering. The main dysfunction is thought to be an impairment in the ability of the basal ganglia to produce timing cues for the initiation of the next motor segment of speech, explaining the association of acquired and re-emergent stuttering with diseases such as dystonia and Parkinson's disease. CLINICAL PICTURE: We describe a 61-year-old man presenting with re-emergent stuttering and mild hypomimia, only to develop unilateral rest tremors, hypo- and bradykinesia, rigidity and gait difficulties one year later. TREATMENT AND OUTCOME: His parkinsonism responded well to treatment with bromocriptine, but he continued to stutter. DISCUSSION: This case illustrates the association between acquired or re-emergent stuttering and basal ganglia disorders, and highlights the need to assess such patients for an underlying aetiology.