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Understanding the dynamics of COVID-19; implications for therapeutic intervention, vaccine development and movement control

Salvamani S, Tan HZ, Thang WJ, Ter HC, Wan MS, Gunasekaran B, et al.

Br J Biomed Sci, 2020 Oct;77(4):168-184.
PMID: 32942955 DOI: 10.1080/09674845.2020.1826136

The COVID-19 disease is caused by the SARS-CoV-2 virus, which is highly infective within the human population. The virus is widely disseminated to almost every continent with over twenty-seven million infections and over ninety-thousand reported deaths attributed to COVID-19 disease. SARS-CoV-2 is a single stranded RNA virus, comprising three main viral proteins; membrane, spike and envelope. The clinical features of COVID-19 disease can be classified according to different degrees of severity, with some patients progressing to acute respiratory distress syndrome, which can be fatal. In addition, many infections are asymptomatic or only cause mild symptoms. As there is no specific treatment for COVID-19 there is considerable endeavour to raise a vaccine against SARS-CoV-2, in addition to engineering neutralizing antibody interventions. In the absence of an effective vaccine, movement controls of varying stringencies have been imposed. Whilst enforced lockdown measures have been effective, they may be less effective against the current strain of SARS-CoV-2, the G614 clade. Conversely, other mutations of the virus, such as the Δ382 variant could reduce the clinical relevance of infection. The front runners in the race to develop an effective vaccine focus on the SARS-Co-V-2 Spike protein. However, vaccines that produce a T-cell response to a wider range of SARS-Co-V-2 viral proteins, may be more effective. Population based studies that determine the level of innate immunity to SARS-CoV-2, from prior exposure to the virus or to other coronaviruses, will have important implications for government imposed movement control and the strategic delivery of vaccination programmes.
Spectrum of cutaneous granulomatous lesions: A 5-year experience in a tertiary care centre in Sarawak

Ting IPL, Tan HZ, Teo HG, Kiing JW, Muniandy P

Med J Malaysia, 2023 Mar;78(2):184-189.
PMID: 36988528

INTRODUCTION: Granulomatous skin lesions can have various histopathological features leading to diagnostic confusion. The study aimed to determine the frequency and pattern of different granulomatous skin lesions.
MATERIALS AND METHODS: This was a 5-year retrospective study done between April 2017 and March 2022 at Dermatology Department, Sarawak General Hospital. Subjects with a clinicopathological diagnosis of granulomatous diseases were included in the analysis.
RESULTS: A total of 1718 skin biopsies were done during the study periods, with 49 (2.8%) confirmed granulomatous skin lesions. Most patients were aged 40-60 with a male predominance of 51%. Most of the skin biopsy samples were taken from the upper limb (36%). In this study, epitheloid granuloma was the commonest subtype (21, 43%) followed by suppurative granuloma (12, 24%), tuberculoid granuloma (8, 16%) and foreign body granuloma (5, 10%). The commonest aetiology of granulomatous skin lesions in our study was infections (30, 61%) followed by foreign body inoculation (8, 16%). Fungal infection was the most common infective cause, followed by cutaneous tuberculosis.
CONCLUSION: The major cause of granulomatous dermatoses in developing countries is still infections, fungal and tuberculosis being the leading causes.
Fulltext A randomized single-dose, two-period crossover bioequivalence study of two fixed-dose Paracetamol/Orphenadrine combination preparations in healthy volunteers under fasted condition

Cheah KY, Mah KY, Pang LH, Ng SM, Wong JW, Tan SS, et al.

BMC Pharmacol Toxicol, 2020 06 23;21(1):45.
PMID: 32576287 DOI: 10.1186/s40360-020-00416-3

BACKGROUND: Paracetamol/Orphenadrine is a fixed dose combination containing 35 mg orphenadrine and 450 mg paracetamol. It has analgesic and muscle relaxant properties and is widely available as generics. This study is conducted to investigate the relative bioavailability and bioequivalence between one fixed dose paracetamol/orphenadrine combination test preparation and one fixed dose paracetamol/orphenadrine combination reference preparation in healthy volunteers under fasted condition for marketing authorization in Malaysia.
METHOD: This is a single-center, single-dose, open-label, randomized, 2-treatment, 2-sequence and 2-period crossover study with a washout period of 7 days. Paracetamol/Orphenadrine tablets were administered after a 10-h fast. Blood samples for pharmacokinetic analysis were collected at scheduled time intervals prior to and up to 72 h after dosing. Blood samples were centrifuged, and separated plasma were kept frozen (- 15 °C to - 25 °C) until analysis. Plasma concentrations of orphenadrine and paracetamol were quantified using liquid-chromatography-tandem mass spectrometer using diphenhydramine as internal standard. The pharmacokinetic parameters AUC0-∞, AUC0-t and Cmax were determined using plasma concentration time profile for both preparations. Bioequivalence was assessed according to the ASEAN guideline acceptance criteria for bioequivalence which is the 90% confidence intervals of AUC0-∞, AUC0-t and Cmax ratio must be within the range of 80.00-125.00%.
RESULTS: There were 28 healthy subjects enrolled, and 27 subjects completed this trial. There were no significant differences observed between the AUC0-∞, AUC0-t and Cmax of both test and reference preparations in fasted condition. The 90% confidence intervals for the ratio of AUC0-t (100.92-111.27%), AUC0-∞ (96.94-108.08%) and Cmax (100.11-112.50%) for orphenadrine (n = 25); and AUC0-t (94.29-101.83%), AUC0-∞ (94.77-101.68%) and Cmax (87.12-101.20%) for paracetamol (n = 27) for test preparation over reference preparation were all within acceptable bioequivalence range of 80.00-125.00%.
CONCLUSION: The test preparation is bioequivalent to the reference preparation and can be used interchangeably.
TRIAL REGISTRATION: NMRR- 17-1266-36,001; registered and approved on 12 September 2017.
Two centuries of biodiversity discovery and loss in Singapore

Chisholm RA, Kristensen NP, Rheindt FE, Chong KY, Ascher JS, Lim KKP, et al.

Proc Natl Acad Sci U S A, 2023 Dec 19;120(51):e2309034120.
PMID: 38079550 DOI: 10.1073/pnas.2309034120

There is an urgent need for reliable data on the impacts of deforestation on tropical biodiversity. The city-state of Singapore has one of the most detailed biodiversity records in the tropics, dating back to the turn of the 19th century. In 1819, Singapore was almost entirely covered in primary forest, but this has since been largely cleared. We compiled more than 200 y of records for 10 major taxonomic groups in Singapore (>50,000 individual records; >3,000 species), and we estimated extinction rates using recently developed and novel statistical models that account for "dark extinctions," i.e., extinctions of undiscovered species. The estimated overall extinction rate was 37% (95% CI [31 to 42%]). Extrapolating our Singapore observations to a future business-as-usual deforestation scenario for Southeast Asia suggests that 18% (95% CI [16 to 22%]) of species will be lost regionally by 2100. Our extinction estimates for Singapore and Southeast Asia are a factor of two lower than previous estimates that also attempted to account for dark extinctions. However, we caution that particular groups such as large mammals, forest-dependent birds, orchids, and butterflies are disproportionately vulnerable.