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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

Characterization of the Lactococcus lactis pepN gene encoding an aminopeptidase homologous to mammalian aminopeptidase N.

The nucleotide sequence of the pepN gene from Lactococcus lactis encoding a zinc-metallo aminopeptidase has been determined. The open reading frame of 2,538 base pairs encodes a protein with a calculated M(r) of 95,368, which agrees with the apparent M(r) of 95,000 of the gene product which was identified by polyclonal antibodies raised against the purified aminopeptidase. The amino acid sequence of the aminopeptidase of L. lactis was found to be similar to the corresponding enzymes of human, rat and mouse, with almost 30% of the residues identical. Also, a highly conserved area was identified which has similarity with the active site of thermolysin. A zinc-binding site, as well as the catalytic site for PepN, is predicted to lie within this conserved stretch. Putative promoter regions upstream of PepN were confirmed by primer extension analysis.

Purification and Characterization of a Dipeptidase from Streptococcus cremoris Wg2.

A dipeptidase was purified to homogeneity from a crude cell extract of Streptococcus cremoris Wg2 by DEAE-Sephacel column chromatography followed by preparative disc gel electrophoresis. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis of the purified enzyme showed a single protein band with a molecular weight of 49,000. The dipeptidase is capable of hydrolyzing a range of dipeptides, but not peptides with longer chains. The enzyme was shown to be a metallo-Mn enzyme with a pH optimum of 8 and a temperature optimum of 50 degrees C. The enzyme is strongly inhibited by thiol-reducing reagents but not by sulfhydryl reagents. Kinetic studies indicated that the enzyme has a relatively low affinity for leucyl-leucine and alanyl-alanine (K(m), 1.6 and 7.9 mM, respectively) but can hydrolyze these substrates at very high rates (V(max), 3,700 and 13,000 mumol/min per mg of protein, respectively).

99Tcm-pyrophosphate myocardial scintigraphy: the role of volume-rendered three-dimensional imaging in the diagnosis of acute myocardial infarction.

The aim of this study was to evaluate the role of volume-rendered three-dimensional imaging in the diagnosis of acute myocardial infarction (AMI) using 99Tcm-pyrophosphate (99Tcm-PYP) scintigraphy in a diagnostically difficult group of patients. In total, 117 patients were studied using planar, single photon emission tomography (SPET) and 3-D volume-rendered imaging performed 3 h after receiving 555 MBq (15 mCi) of 99Tcm-PYP intravenously. 555MBq (15 mCi) of 99Tcm-PYP intravenously. Two teams of physicians reported in a blinded and random fashion on each planar, SPET and 3-D rotating image study. Individual reports were compared with reports that used all three imaging modalities in combination. Observer reproducibility was between 85 and 90% and inter-observer team agreement was between 87 and 91%. A score based on clinical history, electrocardiography, serum cardiac enzyme levels and cardiac risk factors was validated and used as a de facto 'gold standard' for AMI for 75 of the subjects for whom all these details were available. The sensitivity, specificity and overall accuracy of combined planar, SPET and 3-D rotating image modalities were all 84%. Analysis of each modality in isolation showed SPET imaging to have the highest sensitivity (74%) and specificity (89%). In combination with SPET and planar imaging, 3-D rotation image presentation increases diagnostic sensitivity without appreciably altering overall diagnostic accuracy. 99Tcm-PYP myocardial SPET imaging shows good utility in the diagnosis of AMI in diagnostically difficult patients.

Experience with circulatory arrest and hypothermia to facilitate thoracic aortic surgery.

A total of 12 patients underwent surgical repair for thoracic aortic dissections with a technique which included cardiopulmonary bypass, profound hypothermia, high-dose thiopentone and circulatory arrest. Seven of nine early postoperative survivors made a complete recovery on clinical criteria. There were three perioperative deaths and there was one late postoperative death from chronic renal disease. There were no deaths among those operated on electively. Neuropsychological testing may help to define the consequences of circulatory arrest on higher function.

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.