A study of neuropsychiatric manifestations in COVID-19 infection in inpatients and its long-term outcomes in Malaysia.

INTRODUCTION: This study aimed to determine the prevalence and association between the severity of COVID-19 and short and long-term neuropsychiatric symptoms, as well as the risk factors for the development of these symptoms. MATERIALS AND METHODS: A prospective observational study was conducted between 1st October 2021 till September 2022 in the state of Johor, Malaysia. 300 patients with confirmed SARS-CoV-2 infection were randomly selected and followed up for six months. Data were analysed by using Chi-square test, Fisher's Exact test, Paired t test and Multiple logistic regression. RESULTS: The prevalence of short-term neuropsychiatric symptoms was 78%, with anosmia being the most prevalent symptom. Long-term symptoms were found in 22.75% of patients, with headache being the most prevalent (p= 0.001). COVID-19 Stage 2 and 3 infections were associated with a higher risk of short-term neuropsychiatric symptoms, OR for Stage 2 infection was 5.18 (95% CI: 1.48-16.97; p=0.009) and for Stage 3 infection was 4.52 (95% CI: 1.76-11.59; p=0.002). Complete vaccination was a significant predictor of longterm symptoms with adjusted OR 3.65 (95% CI 1.22-10.91; p=0.021). CONCLUSION: This study demonstrated that neuropsychiatric symptoms were common among COVID-19 patients in Johor, Malaysia and the risk of these symptoms was associated with the severity of the infection. Additionally, complete vaccination does not completely protect against long-term neuropsychiatric deficits. This is crucial for continuous monitoring and addressing neuropsychiatric symptoms in COVID-19 survivors.

A retrospective cross-sectional study on the risk factors and survival outcome of End Stage Kidney Disease patients receiving regular maintenance haemodialysis with COVID-19 infection in Hospital Enche' Besar Hajjah Khalsom, Kluang.

INTRODUCTION: COVID-19 pandemic has affected healthcare services around the globe as hospitals were turned into designated hospitals to accommodate high risk groups of patients with COVID-19 infection including end stage kidney disease (ESKD) patients. In Malaysia, there was insufficient data on COVID-19 infection among ESKD patients. This study aims to determine factors and survival outcomes associated with COVID-19 infection among ESKD patients in a designated COVID-19 hospital in Malaysia. METHODS AND MATERIALS: A retrospective cross-sectional study involving 80 haemodialysis (HD) patients recruited from March 2020 till March 2021. Patients' information and results was retrieved and evaluated. Risk factors affecting the COVID-19 mortality were analysed using a one-way analysis of variance (ANOVA) and binary logistic regression. RESULTS: The mean age of the patients was 54 years who were predominantly Malays (87.5%) and living in rural areas. Majority of them had comorbidities such as diabetes mellitus (71%) and hypertension (90%). The most common presentations were fever (46%) and cough (54%) with chest radiographs showing bilateral lower zone ground glass opacities (45%). A quarter of the study population were admitted to the intensive care unit, necessitating mechanical ventilation. This study found that 51% of the patients were given steroids and 45% required oxygen supplementation. The COVID-19 infection mortality among the study population was 12.5%. Simple logistic regression analysis showed that albumin, Odd Ratio, OR=0.85 (95% Confidence Interval, 95%CI: 0.73, 0.98)) and absolute lymphocyte count OR=0.08 (95%CI: 0.11, 0.56) have inverse association with COVID-19 mortality. C-reactive protein OR=1.02 (95%CI: 1.01, 1.04), lactate dehydrogenase OR=1.01 (95%CI: 1.00, 1.01), mechanical ventilation OR=17.21 (95%CI: 3.03, 97.67) and high dose steroids OR=15.71 (95%CI: 1.80, 137.42) were directly associated with COVID-19 mortality. CONCLUSION: The high mortality rate among ESKD patients receiving HD was alarming. This warrants additional infection control measures to prevent the spread of COVID- 19 infection among this vulnerable group of patients. Expediting vaccination efforts in this group of patients should be advocated to reduce the incidence of complications from COVID-19 infection.

Investigation on the Curvature Correction Factor of Extension Spring.

The curvature correction factor is an important parameter in the stress calculation formulation of a helical extension spring, which describes the effect of spring wire curvature on the stress increase towards its inner radius. In this study, the parameters affecting the curvature correction factor were investigated through theoretical and numerical methods. Several finite element (FE) models of an extension spring were generated to obtain the distribution of the tensile stress in the spring. In this investigation, the hook orientation and the number of coils of the extension spring showed significant effects on the curvature correction factor. These parameters were not considered in the theoretical model for the calculation of the curvature correction factor, causing a deviation between the results of the FE model and the theoretical approach. A set of equations is proposed for the curvature correction factor, which relates both the spring index and the number of coils. These equations can be applied directly to the design of extension springs with a higher safety factor.

Predictors of Non-adherence to Immunosuppressive Therapy in Asian Liver Transplant Recipients.

BACKGROUND: Adherence to immunosuppressive medications has been shown to affect post-transplant outcomes. We aimed to determine the level of adherence to immunosuppressive therapy in liver transplant (LT) recipients and to elucidate factors associated with it, as well as patient preferences on the dosing schedule. METHODS: LT recipients were recruited during transplant clinic follow-up. A validated Morisky 8-item questionnaire was completed by patients to assess their adherence to immunosuppressive therapy. Adherence was determined by the sum of the responses to the questionnaire. Low, medium, and high adherence were defined by a Morisky score of >2, 1 to 2, and 0, respectively. Data on the patient's socio-economic and clinical background, dosing schedule of immunosuppressant medications, and patient preferences were included in the questionnaire. RESULTS: A total of 107 LT recipients were approached and 75 completed the questionnaire. The majority of patients (48/74, 64.9%) preferred a once-daily medication regimen. The proportion of high adherence was 24/75 (32.0%), medium adherence was 51/75 (42.7%), and low adherence was 19/75 (25.3%). Multivariate analysis showed younger age and post-transplant duration >5 years as independent predictors for low adherence. Among low-adherence patients, 16/19 (84.2%) patients were on a twice-daily regimen, and, of these, 14/16 (87.5%) preferred their medications to be reduced to once daily. CONCLUSIONS: A significant proportion (68%) of LT recipients had low to moderate adherence to medications, with younger age and longer post-transplant duration of >5 years as independent predictors. Early identification of at-risk patients is essential to allow implementation of measures to improve adherence. Simplifying medication regimens to once daily is a potential way to improve adherence.

SERPINB3 is associated with TGF-ß1 and cytoplasmic ß-catenin expression in hepatocellular carcinomas with poor prognosis.

BACKGROUND: Hepatocellular carcinoma (HCC) is one of the most important sanitary problems for its prevalence and poor prognosis. To date, no information is available on the prognostic value of the ov-serpin SERPINB3, detected in primary liver cancer but not in normal liver. The aim of the study was to analyse SERPINB3 expression in liver cancer in relation with molecular signatures of poor prognosis and with clinical outcome. METHODS: Liver tumours of 97 patients were analysed in parallel for SERPINB3, TGF-ß and ß-catenin. In a subgroup of 67 patients with adequate clinical follow-up, the correlation of molecular findings with clinical outcome was also carried out. RESULTS: High SERPINB3 levels were detectable in 22% of the patients. A significant correlation of this serpin with TGF-ß at transcription and protein level was observed, whereas for ß-catenin a strong correlation was found only at post-transcription level. These findings were in agreement with transcriptome data meta-analysis, showing accumulation of SERPINB3 in the poor-prognosis subclass (S1). High levels of this serpin were significantly associated with early tumour recurrence and high SERPINB3 was the only variable significantly associated with time to recurrence at multivariate analysis. CONCLUSIONS: SERPINB3 is overexpressed in the subset of the most aggressive HCCs.

Resolution of adefovir-related nephrotoxicity by adefovir dose-reduction in patients with chronic hepatitis B.

BACKGROUND: Chronic hepatitis B patients (CHB) treated with adefovir were followed up to evaluate nephrotoxicity and its outcome. AIM: To assess the incidence of renal dysfunction during adefovir therapy in Asian patients and factors associated with it, and evaluate strategies to improve adefovir-related renal dysfunction and their impact on viral suppression. METHODS: Chronic hepatitis B clinic patients from a tertiary hospital on adefovir treatment, with their clinical and laboratory parameters were extracted from the hospital electronic clinical database in an observational study design. Patients were excluded if they had liver/renal transplant, baseline renal impairment or were on dialysis. Adefovir-related renal dysfunction was defined as adefovir-related abnormal serum creatinine (ARASC) > 125 µmol/L (males), >90 µmol/L (females); adefovir-related abnormal GFR <60 mL/min; and adefovir-related increased serum creatinine >0.5 mg/dL, without other known causes of nephrotoxicity. RESULTS: A total of 271/383 adefovir-treated patients were suitable for analysis and 33(12%) patients developed abnormal serum creatinine. Cumulative increase in proportion of patients with ARASC was 33.8% and GFR ≤60 mL/min was 38.3% by 6 years, while serum creatinine increase ≥0.5 mg/dL was 21.48% by 5 years. Using multivariate analysis, the only independent baseline predictor of ARASC was GFR ≤76.1 mL/min. Patients who had ARASC had similar levels of viral suppression to those who did not have ARASC. Those who had ARASC either continued adefovir (24%), switched therapy (24%) or had adefovir dose reduction (52%). ARASC resolved and GFR normalised in almost all patients after either switching therapy or reducing adefovir dose, with no difference between the two strategies (P = 0.737). Those with adefovir dose reduction had no significant increase in HBV DNA (P = 0.170). CONCLUSIONS: Adefovir-related renal dysfunction occurred in a significant number of adefovir-treated patients, but reduction of the dose led to renal improvement without compromising treatment efficacy.

A dynamic plasmonic manipulation technique assisted by phase modulation of an incident optical vortex beam.

A novel phase modulation method for dynamic manipulation of surface plasmon polaritons (SPPs) with a phase engineered optical vortex (OV) beam illuminating on nanoslits is experimentally demonstrated. Because of the unique helical phase carried by an OV beam, dynamic control of SPP multiple focusing and standing wave generation is realized by changing the OV beam's topological charge constituent with the help of a liquid-crystal spatial light modulator. Measurement of SPP distributions with near-field scanning optical microscopy showed an excellent agreement with numerical predictions. The proposed phase modulation technique for manipulating SPPs features has seemingly dynamic and reconfigurable advantages, with profound potential for development of SPP coupling, routing, multiplexing and high-resolution imaging devices on plasmonic chips.

Phase singularity of surface plasmon polaritons generated by optical vortices.

We demonstrate an experimental result that shows the phase singularity of surface plasmon waves generated by the direct transform of optical vortices at normal incidence focused on a structureless metal surface. The near-field two-dimensional intensity distribution near the focal plane is experimentally examined by using near-field scanning optical microscopy and shows a good agreement with the finite-difference time-domain simulation result. The experimental realization demonstrates a potential of the proposed excitation scheme to be reconfigured locally with advantages over structures milled into optically thick metallic films for plasmonics applications involving plasmonic vortices.

Manipulation of surface plasmon polaritons by phase modulation of incident light.

Manipulation of surface plasmon polaritons (SPP) by phase modulation of incident light beams is proposed with analytical and numerical verifications when an optical vortex (OV) beam is employed as an example. Fundamental functionalities of a plasmonic chip such as in-plane focusing, coupling and multiplexing of SPP by sequentially varying the topological charge of OV beam are demonstrated. Complementary to the manually-controlled optical-path-different technique reported in literature, the proposed method reveals a direct phase transform from OV beam to SPP with dynamic and reconfigurable advantages.

Deterministic relief dielectric structures to realize phase modulation of surface-plasmon polaritons.

We propose a modified effective-refractive-index model for the design of relief dielectric structures on a metal surface to realize phase modulation of surface-plasmon polaritons (SPPs). In this model, the length of the dielectric structure is optimized to reach phase shifting between the SPP waves transmitted through dielectric structure and those directly propagated with the consideration of SPP losses. Specifically, a one-dimensional dielectric Fresnel zone plate is designed by employing the proposed model to demonstrate phase modulation of SPPs for the highest focusing efficiency.

Structured light for focusing surface plasmon polaritons.

We propose a structureless method for focusing surface plasmon polaritons (SPPs) on a flat metal film under illumination of radially polarized cogwheel-like structured light beams. Without metal structures, the locally induced SPPs can further be propagated following the predefined patterns to form symmetric focal spots with dimensions beyond diffraction limit. Benefiting from the radial polarization, this method can be employed to pattern various center-symmetric evanescent distributions for generating SPPs reconfigurably. The SPPs will be propagating and focusing in radial directions.

Analysis of surface plasmon interference pattern formed by optical vortex beams.

Following our recent experimental approach to excitation of surface plasmon polaritons induced by optical vortex beams [5], we report further analysis and verification of the surface plasmon interference pattern formed by locally excited standing surface plasmon polaritons in a metal/dielectric film. Our simulation model can be demonstrated by using angular spectrum representation. The generated standing interference pattern has potential as a resolution enhancement technique for sub-diffraction imaging.

Cardiovascular effects of angiotensin II in the rostral ventrolateral medulla: the push-pull hypothesis.

Neurons within the rostral ventrolateral medulla (RVLM) play a pivotal role in the tonic and phasic control of blood pressure. This region also contains a high density of angiotensin II type 1 (AT1) receptors. There is evidence that tonic activation of AT1 receptors in the RVLM contributes to an increased sympathetic vasomotor activity in some models of hypertension. At the same time, under certain conditions, activation of AT1 receptors in the RVLM can cause sympathoinhibition. In this review we argue that the effect of endogenous angiotensin II in the RVLM on sympathetic vasomotor activity depends upon the balance between tonic excitatory and inhibitory effects on sympathetic premotor neurons mediated by AT1 receptors within this region, and that this balance may be altered in different physiological or pathophysiological conditions.

Long-term regulation of arterial blood pressure by hypothalamic nuclei: some critical questions.

1. The long-term level of arterial pressure is dependent on the relationship between arterial pressure and the urinary output of salt and water, which, in turn, is affected by a number of factors, including renal sympathetic nerve activity (RSNA). In the present brief review, we consider the mechanisms within the brain that can influence RSNA, focusing particularly on hypothalamic mechanisms. 2. The paraventricular nucleus (PVN) in the hypothalamus has major direct and indirect connections with the sympathetic outflow and there is now considerable evidence that tonic activation of the PVN sympathetic pathway contributes to the sustained increased level of RSNA that occurs in conditions such as heart failure and neurogenic hypertension. The tonic activity of PVN sympathetic neurons, in turn, depends upon the balance of excitatory and inhibitory inputs. A number of neurotransmitters and neuromodulators are involved in these tonic excitatory and inhibitory effects, including glutamate, GABA, angiotensin II and nitric oxide. 3. The dorsomedial hypothalamic nucleus (DMH) also exerts a powerful influence over sympathetic activity, including RSNA, via synapses with sympathetic nuclei in the medulla and, possibly, also other brainstem regions. The DMH sympathetic pathway is an important component of the phasic sympathoexcitatory responses associated with acute stress, but there is no evidence that it is an important component of the central pathways that produce long-term changes in arterial pressure. Nevertheless, it is possible that repeated episodic activation of this pathway could lead to vascular hypertrophy and, thus, sustained changes in vascular resistance and arterial pressure. 4. Recent studies have reactivated the old debate concerning the possible role of the baroreceptor reflex in the long-term regulation of sympathetic activity. Therefore, central resetting of the baroreceptor-sympathetic reflex may be an important component of the mechanisms causing sustained changes in RSNA. However, little is known about the cellular mechanisms that could cause such resetting.

Comparison of faecal Lactobacillus populations in experimental animals from different breeding facilities and possible consequences for probiotic studies.

AIMS: The effect of probiotic lactobacilli is likely dependent on the indigenous Lactobacillus strains in the intestinal tract. Since a substantial number of probiotic studies is performed in rodents, we compared the Lactobacillus strains of different rat and mouse populations in three animal facilities. METHODS AND RESULTS: SDS-PAGE and 16S rDNA analysis of cultured faecal lactobacilli revealed that different Lactobacillus strains were detected in genetically similar Wistar rats bred at different locations. Further, within the same animal facility host genetics did not affect the types of the predominant lactobacilli strains. CONCLUSIONS: Our results show that the environmental background of laboratory animals rather than host genetics determines the indigenous Lactobacillus strains that are found. SIGNIFICANCE AND IMPACT OF THE STUDY: Our findings underline the importance of microflora analysis in probiotic studies.

Clinical features of Nipah virus encephalitis among pig farmers in Malaysia.

BACKGROUND: Between September 1998 and June 1999, there was an outbreak of severe viral encephalitis due to Nipah virus, a newly discovered paramyxovirus, in Malaysia. METHODS: We studied the clinical features of the patients with Nipah virus encephalitis who were admitted to a medical center in Kuala Lumpur. The case definition was based on epidemiologic, clinical, cerebrospinal fluid, and neuroimaging findings. RESULTS: Ninety-four patients with Nipah virus infection were seen from February to June 1999 (mean age, 37 years; ratio of male patients to female patients, 4.5 to 1). Ninety-three percent had had direct contact with pigs, usually in the two weeks before the onset of illness, suggesting that there was direct viral transmission from pigs to humans and a short incubation period. The main presenting features were fever, headache, dizziness, and vomiting. Fifty-two patients (55 percent) had a reduced level of consciousness and prominent brain-stem dysfunction. Distinctive clinical signs included segmental myoclonus, areflexia and hypotonia, hypertension, and tachycardia and thus suggest the involvement of the brain stem and the upper cervical spinal cord. The initial cerebrospinal fluid findings were abnormal in 75 percent of patients. Antibodies against Hendra virus were detected in serum or cerebrospinal fluid in 76 percent of 83 patients tested. Thirty patients (32 percent) died after rapid deterioration in their condition. An abnormal doll's-eye reflex and tachycardia were factors associated with a poor prognosis. Death was probably due to severe brain-stem involvement. Neurologic relapse occurred after initially mild disease in three patients. Fifty patients (53 percent) recovered fully, and 14 (15 percent) had persistent neurologic deficits. CONCLUSIONS: Nipah virus causes a severe, rapidly progressive encephalitis with a high mortality rate and features that suggest involvement of the brain stem. The infection is associated with recent contact with pigs.