Upper Respiratory Tract Infection Trends in a Psychiatric Institute in Singapore.

OBJECTIVES: To compare the incidence of upper respiratory tract infection (URTI) between inpatients at the Institute of Mental Health in Singapore and the general population over 8 years to determine the effectiveness of our infection control strategies. METHODS: Data for cases of influenza and URTI at our institute between January 2012 and December 2019 were collected. National data were derived from weekly infectious disease bulletins that report daily averages of people attending polyclinics/surgeries with influenza and URTI. Interrupted time series analyses were used to determine the impact of infection prevention and control strategies on incidence. RESULTS: Over the 8 years, there were 1607 cases of URTI involving 182 clusters, equal to 3.16 cases per 10 000 patient-bed-days. 965 (60%) cases and 95 (52%) clusters occurred in long-stay wards, whereas 642 (40%) cases and 87 (48%) clusters occurred in acute wards. The median cluster size was 12 in the long-stay wards and 7 in the acute wards (p < 0.0001). The spikes in cases in June and December may be attributed to the increased staff and visitor mobility during school vacations in June and December. Strategies implemented during the study period did not significantly reduce the incidence of URTI. Previous strategies implemented in 2005 to meet accreditation standards are more likely to be contributors. CONCLUSION: Infection control strategies of our institute appear to be effective, because the incidence of URTI was lower in our institute than in the community. The similar incidence of URTI in acute and long-stay wards indicates that service-user turnover is not a contributor. Rather, staff and visitors are more likely to be the vector. The larger clusters in long-stay wards indicates a greater risk of transmission in such settings. Increased activity in our institute during school vacations may be associated with an increase in cases in June and December. It is difficult to determine if strategies implemented during the study period successfully reduce the incidence of URTI.

The NALCN channel complex is voltage sensitive and directly modulated by extracellular calcium.

The sodium leak channel (NALCN) is essential for survival in mammals: NALCN mutations are life-threatening in humans and knockout is lethal in mice. However, the basic functional and pharmacological properties of NALCN have remained elusive. Here, we found that robust function of NALCN in heterologous systems requires co-expression of UNC79, UNC80, and FAM155A. The resulting NALCN channel complex is constitutively active and conducts monovalent cations but is blocked by physiological concentrations of extracellular divalent cations. Our data support the notion that NALCN is directly responsible for the increased excitability observed in a variety of neurons in reduced extracellular Ca2+. Despite the smaller number of voltage-sensing residues in NALCN, the constitutive activity is modulated by voltage, suggesting that voltage-sensing domains can give rise to a broader range of gating phenotypes than previously anticipated. Our work points toward formerly unknown contributions of NALCN to neuronal excitability and opens avenues for pharmacological targeting.

Chemical modification of proteins by insertion of synthetic peptides using tandem protein trans-splicing.

Manipulation of proteins by chemical modification is a powerful way to decipher their function. However, most ribosome-dependent and semi-synthetic methods have limitations in the number and type of modifications that can be introduced, especially in live cells. Here, we present an approach to incorporate single or multiple post-translational modifications or non-canonical amino acids into proteins expressed in eukaryotic cells. We insert synthetic peptides into GFP, NaV1.5 and P2X2 receptors via tandem protein trans-splicing using two orthogonal split intein pairs and validate our approach by investigating protein function. We anticipate the approach will overcome some drawbacks of existing protein enigineering methods.

Tracking the mental health of a nation: prevalence and correlates of mental disorders in the second Singapore mental health study.

AIMS: The second Singapore Mental Health Study (SMHS) - a nationwide, cross-sectional, epidemiological survey - was initiated in 2016 with the intent of tracking the state of mental health of the general population in Singapore. The study employed the same methodology as the first survey initiated in 2010. The SMHS 2016 aimed to (i) establish the 12-month and lifetime prevalence and correlates of major depressive disorder (MDD), dysthymia, bipolar disorder, generalised anxiety disorder (GAD), obsessive compulsive disorder (OCD) and alcohol use disorder (AUD) (which included alcohol abuse and dependence) and (ii) compare the prevalence of these disorders with reference to data from the SMHS 2010. METHODS: Door-to-door household surveys were conducted with adult Singapore residents aged 18 years and above from 2016 to 2018 (n = 6126) which yielded a response rate of 69.0%. The subjects were randomly selected using a disproportionate stratified sampling method and assessed using World Health Organization Composite International Diagnostic Interview version 3.0 (WHO-CIDI 3.0). The diagnoses of lifetime and 12-month selected mental disorders including MDD, dysthymia, bipolar disorder, GAD, OCD, and AUD (alcohol abuse and alcohol dependence), were based on the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV) criteria. RESULTS: The lifetime prevalence of at least one mood, anxiety or alcohol use disorder was 13.9% in the adult population. MDD had the highest lifetime prevalence (6.3%) followed by alcohol abuse (4.1%). The 12-month prevalence of any DSM-IV mental disorders was 6.5%. OCD had the highest 12-month prevalence (2.9%) followed by MDD (2.3%). Lifetime and 12-month prevalence of mental disorders assessed in SMHS 2016 (13.8% and 6.4%) was significantly higher than that in SMHS 2010 (12.0% and 4.4%). A significant increase was observed in the prevalence of lifetime GAD (0.9% to 1.6%) and alcohol abuse (3.1% to 4.1%). The 12-month prevalence of GAD (0.8% vs. 0.4%) and OCD (2.9% vs. 1.1%) was significantly higher in SMHS 2016 as compared to SMHS 2010. CONCLUSIONS: The high prevalence of OCD and the increase across the two surveys needs to be tackled at a population level both in terms of creating awareness of the disorder and the need for early treatment. Youth emerge as a vulnerable group who are more likely to be associated with mental disorders and thus targeted interventions in this group with a focus on youth friendly and accessible care centres may lead to earlier detection and treatment of mental disorders.

Determination of lewisite constituents in aqueous samples using hollow-fibre liquid-phase microextraction followed by gas chromatography-mass spectrometry.

The applicability of hollow-fibre liquid-phase microextraction for extracting 2-chlorovinyldichloroarsine (lewisite 1), bis(2-chlorovinyl)chloroarsine (lewisite 2), tris(2-chlorovinyl)arsine (lewisite 3) and arsenic trichloride from aqueous samples is reported. Parameters affecting the extraction efficiency of these chemicals were optimised. These parameters included the type of derivatising agent, extraction solvent, derivatisation method, pH, ionic strength, stirring speed and extraction time. A linear range between 0.002 and 0.2 µg/mL was established for the lewisites with good square regression coefficients (0.9955-0.9992). Good reproducibility with relative standard deviations (RSDs) from 8 to 10% was achieved. The limit of detection was 0.002 µg/mL for the lewisites and 0.005 µg/mL for arsenic trichloride (3:1 signal-to-noise ratio). The extraction method was validated with a proficiency test sample issued by the Organisation for the Prohibition of Chemical Weapons (OPCW). The rapidity and precision of the new method should help deter against the employment of lewisite as a chemical warfare agent: its use could be confirmed easily from analysis of aqueous samples.

Ministry of Health clinical practice guidelines: depression.

The Ministry of Health (MOH) have updated the clinical practice guidelines on Depression to provide doctors and patients in Singapore with evidence-based treatment for depression. This article reproduces the introduction and executive summary (with recommendations from the guidelines) from the MOH clinical practice guidelines on Depression, for the information of readers of the Singapore Medical Journal. Chapters and page numbers mentioned in the reproduced extract refer to the full text of the guidelines, which are available from the Ministry of Health website: http://www.moh.gov.sg/content/moh_web/home/Publications/guidelines/cpg/2012/depression.html. The recommendations should be used with reference to the full text of the guidelines. Following this article are multiple choice questions based on the full text of the guidelines.

Brain attack: needing resuscitation.

The brain is extremely susceptible to focal ischaemia. Following vascular occlusion, a core of severely damaged brain tissue develops, surrounded by an ischaemic penumbra. This potentially-salvageable penumbra may be estimated by advanced neuroimaging techniques, particularly by diffusion-perfusion mismatch. Clinical trials have demonstrated the efficacy of intravenous thrombolysis within three hours of onset of ischaemic stroke in reducing short-term disability. Recanalisation is enhanced by intra-arterial thrombolysis, sonothrombolysis and clot-retrieval devices. Occasionally, reperfusion injury may lead to clinical deterioration. The search continues for effective neuroprotectants. Brain perfusion needs to be maintained through blood and intracranial pressure management. Hemicraniectomy for 'malignant' cerebral oedema reduces death and disability. Elevated glucose should be controlled and hypoxia alleviated. Public education of symptoms and the need for immediate presentation to a medical facility is needed. Stroke unit care reduces death and disability with little increase in cost. Current evidence supports urgent efforts to resuscitate the brain after stroke.

Suicide in Asia.

Suicide is a major problem worldwide, and suicides in Asian countries account for as much as 60% of all suicides in the world. There are many unique features in suicides within this ethnically-diverse continent, from the methods used, to the putative risk factors. Much research still needs to be done to guide efficacious and culturally relevant interventions in suicide prevention; existing literature suggests a strong focus for programmes that address restricting access to pesticides, increasing crisis counseling activities, improving the accessibility and delivery of mental health services, and promoting responsible media reporting of suicide and related issues. There is a need for coordinated national suicide plans to be developed that are sensitive to the socioeconomic and cultural factors in the local context.

Glutamatergic abnormalities of the thalamus in schizophrenia: a systematic review.

The thalamus, a key information processing centre in facilitating sensory discrimination and cognitive processes, has been implicated in schizophrenia due to the increasing evidence showing structural and functional thalamic abnormalities. Glutamatergic abnormalities, in particular, have been examined since glutamate is one of the main neurotransmitters found in the thalamus. We aimed to review the existing literature (1978 till 2007) on post-mortem and in vivo studies of the various components of glutamatergic neurotransmission as well as studies of the glutamate receptor genes within the thalamus in schizophrenia. The literature search was done using multiple databases including Scopus, Web of Science, EBSCO host, Pubmed and ScienceDirect. Keywords used were "glutamate", "thalamus", "schizophrenia", "abnormalities", and "glutamatergic". Further searches were made using the bibliographies in the main journals and related papers were obtained. The extant data suggest that abnormalities of the glutamate receptors as well as other molecules involved in glutamatergic neurotransmission (including glutamate transporters and associated proteins, N-methyl D-aspartate (NMDA) receptor-associated intracellular signaling proteins, and glutamatergic enzymes) are found within the thalamus in schizophrenia. There is a pressing need for more rapid replication of findings from post mortem and genetic studies as well as the promotion of multi-component or multi-modality assessments of glutamatergic anomalies within the thalamus in order to allow a better appreciation of disruptions in these molecular networks in schizophrenia. These and future findings may represent potential novel targets for antipsychotic drugs to ameliorate the symptoms of schizophrenia.

Use of ligase chain reaction in early diagnosis of tuberculous meningitis.

INTRODUCTION: Nucleic acid-based amplification tests are currently licensed only for the detection of Mycobacterium tuberculosis in pulmonary specimens. There are insufficient data for extrapulmonary specimens. The aim of this study is to investigate the diagnostic value of these investigations in tuberculous meningitis. MATERIALS AND METHODS: We performed a prospective study using a commercial ligase chain reaction DNA amplification technique [Ligase chain result (LCx) M. tuberculosis; Abbott Laboratories, Abbott Park, IL, USA] on cerebrospinal fluid (CSF) to diagnose tuberculous meningitis and compared the results with standard microbiological data. Conflicting cases were resolved according to the final clinical diagnosis. A total of 54 CSF specimens from 54 patients were tested. RESULTS: Six (11.1%) specimens were culture-positive for M. tuberculosis; of these, only 1 (1.9%) was smear-positive. The sensitivity, specificity, positive predictive value and negative predictive value of the LCx assay, compared with culture results, were 66.7%, 100%, 100% and 96%, respectively. After resolution according to clinical data, the sensitivity, specificity, positive predictive value and negative predictive value were 33.3%, 100%, 100% and 75%, respectively. All controls had negative LCx results. There were no false positives. CONCLUSION: LCx assay is highly specific and complements conventional laboratory diagnostic methods (CSF smear and culture) in the diagnosis of tuberculous meningitis. In the appropriate clinical context, a positive result is strongly suggestive of tuberculosis and could enable antituberculous treatment to be started immediately.

Quantitative three-dimensional anatomy of cervical, thoracic and lumbar vertebrae of Chinese Singaporeans.

This paper details the quantitative three-dimensional anatomy of cervical, thoracic and lumbar vertebrae (C3-T12) of Chinese Singaporean subjects based on 220 vertebrae from 10 cadavers. The purpose of the study was to measure the linear dimensions, angulations and areas of individual vertebra, and to compare the data with similar studies performed on Caucasian specimens. Measurements were taken with the aid of a three-dimensional digitiser. The means and standard errors for linear, angular and area dimensions of the vertebral body, spinal canal, pedicle, and spinous and transverse processes were obtained for each vertebra. Compared to the Caucasian data, all the dimensions were found to be smaller. Of significance were the spinal canal area, and pedicle width and length, which were smaller by 31.7%, 25.7% and 22.1% on average, respectively. A slight divergence, instead of convergence, was found from T8 to T12. According to the findings, the use of a transpedicle screw may not be feasible. The results can also provide more accurate modelling for analysis and design of spinal implants and instrumentations, and also allow more precise clinical diagnosis and management of the spine in Chinese Singaporeans.

Attention-deficit/hyperactivity disorder in adult patients with posttraumatic stress disorder (PTSD): is ADHD a vulnerability factor?

OBJECTIVE: There is limited evidence suggesting a link between posttraumatic stress disorder (PTSD) and Attention-Deficit/ Hyperactivity Disorder (ADHD). This study examined the association between PTSD and ADHD using retrospective and current clinical evaluations. METHOD: Twenty-five male veterans with PTSD and 22 male veterans with panic disorder were evaluated for ADHD. The data was analyzed using chi-square and student's t-tests. RESULTS: Thirty-six percent of participants with PTSD and 9% of participants with panic disorder met criteria for childhood ADHD. Twenty-eight percent of participants with PTSD and 5% of participants with panic disorder met criteria for current ADHD. CONCLUSIONS: There appears to be a significant association of PTSD with ADHD. ADHD or common predisposing factors may increase the vulnerability for developing PTSD.

Gluteal compartment syndrome misdiagnosed as deep vein thrombosis.

Gluteal compartment syndrome usually occurs secondary to prolonged immobility and recumbency following alcohol and drug abuse. The resultant pain and swelling in the lower limb may be misdiagnosed as deep vein thrombosis. Once compartment syndrome is diagnosed, urgent decompression fasciotomy is required. The outcome is poor if the diagnosis is missed or delayed. We report such a case.

Turnup turndown of membrane operation of membrane bioreactors.

Membrane bioreactors can be operated with intermittent permeation and continuous aeration. Aeration close to the surface of a submerged membrane helps to maintain a membrane surface that is free from fouling. The conditions under which this occurs depend on the interaction between flux and aeration rate. Increased flux is possible without severe fouling if the aeration rate is increased. Results of performing membrane operation under the dual intermittency of aeration rate and permeation rate, with permeation also interrupted on a regular cycle, are presented. The results show that membrane plants designed for optimal operation at moderate flux can survive effectively with higher flux operation for restricted periods. Designing to account for such effects could reduce overall plant costs.

MRI findings in osmotic myelinolysis.

OBJECTIVES: Osmotic myelinolysis is a distinctive clinical syndrome with characteristic CT and MR features. This study was undertaken to determine the MR appearance of these lesions on T1 and T2-weighted, and diffusion-weighted imaging (DWI) sequences with apparent diffusion coefficient (ADC) mapping. MATERIALS AND METHODS: We describe six patients who presented with deranged serum sodium levels and subsequently developed osmotic myelinolysis. CT and MRI scans were retrospectively reviewed, including the advanced functional MR sequence of DWI with ADC mapping. RESULTS: Both cerebral white matter and pontine lesions were typically hypo and hyper-intense on T1 and T2W sequences respectively. Lesions were mildly hyperintense on isotropic DWI images with elevation of the ADC. CONCLUSION: MRI is superior to CT in depicting lesions in osmotic myelinolysis. DWI with ADC mapping suggests that osmotic myelinolysis is not simply a demyelinating disorder but has similarities to multiple sclerosis.

Quantitative three-dimensional anatomy of lumbar vertebrae in Singaporean Asians.

This paper details the quantitative three-dimensional anatomy of lumbar vertebrae L1-L5 from Asian (Singaporean) subjects based on 60 lumbar vertebrae from 12 cadavers. The purpose of the study was to measure the dimensions of the various parameters of the lumbar vertebrae and thereafter to compare the data with a study performed on Caucasian specimens. Measurements were taken with the aid of a three-dimensional digitiser. The means and standard errors for linear, angular and area dimensions of the vertebral body, spinal canal, pedicle, and spinous and transverse processes were obtained for each lumbar vertebra. From this comparison, it was found that the dimensions of the vertebral body of the Asian subjects are slightly larger, with a maximum average difference of 8% for the posterior vertebral body height. The dimensions of the spinal canal, pedicle, and spinous and transverse processes of Asian subjects are smaller. The greatest difference can be found in the spinal canal area and pedicle width, which are smaller by an average of 30% and 20%, respectively. With the exception of the spinal canal depth, spinal canal area and pedicle width, all other parameters compared show a similar trend. The findings can provide more accurate modelling for analysis and spinal implant design and also allow more precise clinical diagnosis in sub-Asian groups.

Heparin induced thrombocytopenia.

BACKGROUND: Heparin is a widely used antithrombotic agent for treatment of ischemic cerebrovascular disease. One of its most important side-effects is thrombocytopenia which may lead to potentially life-threatening haemorrhagic and thrombotic complications. METHODS: We performed a prospective study to determine the frequency of heparin induced thrombocytopenia. Heparin induced thrombocytopenia is defined as a platelet count of less than 150 x 10(3)/mm3 or a decrease in platelet count to 30% to 50% from baseline. Daily platelet counts were obtained in 50 adult patients who were treated with the same lot of intravenous bovine heparin. Two patients (4%) developed thrombocytopenia with onset varying from four to seven days after heparin was started. In both cases, platelet counts returned to baseline levels three to five days after cessation of therapy. No ischemic or haemorrhagic complications occurred. CONCLUSION: Heparin induced thrombocytopenia is a common complication of intravenous heparin treatment. Clinicians treating patients with heparin should determine platelet counts at baseline and henceforth at regular intervals beginning from the fifth day of therapy. We recommend commencement of warfarin therapy concurrently with heparin infusion and discontinuation of heparin once warfarin has become effective. All doctors must be vigilant to this reversible common complication.

Advances in neurointensive care.

PURPOSE: To highlight recent advances in neurological and neurosurgical intensive care. DATA SOURCES: A MEDLINE search was conducted from January 1980 to August 2000. Keywords included intensive care, head injury, subarachnoid haemorrhage, status epilepticus, myasthenic crisis, Guillain-Barre syndrome and stroke. All articles in English were considered for review. Additional articles were identified from the references of the retrieved articles and cross-referencing selected articles. DATA EXTRACTION: All clinical studies, review articles and abstracts were reviewed. DATA SYNTHESIS: Rapid advances in neurological and neurosurgical intensive care in the last decade have led to the development of specialised neurointensive care units with joint ventures between neurology and neurosurgery. Work in these units have contributed immensely to our understanding of the pathophysiology and management of acute brain injury. The principles of intensive care management include amelioration or reversal of brain injury and preservation of normal neural tissue. Treatment algorithms are possible with the aid of intense clinical and neurophysiologic monitoring. Ongoing clinical and basic science research may provide new treatment options for the intensivist in the acute phase of brain injury. CONCLUSION: Specialised neurointensive care units provide the best environment for the patient with acute brain injury. Outcome is frequently enhanced the clinicians skilled towards dealing with the whole spectrum of neurologic insults.

Neuroprotection in acute stroke.

PURPOSE: To highlight recent advances in neuroprotection in acute stroke. DATA SOURCES: A MEDLINE search was conducted from January 1985 to November 2000. Key words included neuroprotection, cerebrovascular, subarachnoid haemorrhage, perioperative stroke, hypothermia and apopotosis. All articles in English were considered for review. Additional articles were identified from the references of the retrieved articles and cross-referencing selected articles. DATA EXTRACTION: All clinical studies and review articles and abstracts were reviewed. DATA SYNTHESIS: The neuronal cells of the central nervous system are susceptible to various forms of insult such as ischaemia and haemorrhage. Each step along the ischaemic cascade is a potential target for therapeutic intervention. Neuroprotective agents are designed to minimise cellular injury and salvage brain tissue. In cerebral ischaemia, only thrombolysis had been shown to improve clinical outcome. Neuroprotective therapy has definite benefits in animals but not in humans. It may potentially extend the time window for thrombolysis. In aneurysmal subarachnoid haemorrhage, the only agent with proven efficacy is nimodipine. Research is ongoing in the development of new drugs. Currently several phase III trials are in progress. CONCLUSION: There is substantial optimism in the development of neuroprotective therapy to improve outcome in stroke patients.

Awareness of tardive dyskinesia in Asian patients with schizophrenia.

While ethnocultural differences in risk of tardive dyskinesia (TD) have been suggested, no previous studies have examined whether this factor also plays a role in lack of awareness of TD. This study examined this question in an Asian population with schizophrenia. Six hundred seven patients in a state mental hospital in Singapore were assessed using the Abnormal Involuntary Movement Scale (AIMS) and the Simpson-Angus Rating Scale. Of the 607 patients, 242 (39.9%) met criteria for TD, and 163 (67.4%) patients were not aware of the presence of TD. No significant differences in terms of age, gender, and duration of illness were found between those aware of their TD and those not aware. Daily neuroleptic doses and scores for the AIMS and Simpson-Angus Rating Scale were significantly different, although after logistic regression, only the Simpson-Angus Rating Scale scores remained significant. The finding that a large proportion of our patients lacked awareness of their TD is consistent with other reports in the West and provides evidence that this feature is characteristic of the illness rather than of a specific ethnocultural group. We found an association between lack of awareness and greater severity of extrapyramidal symptoms (EPS), suggesting that there may be a subtype of TD in which lack of awareness and greater vulnerability of developing EPS are features.