Genome Profiling of SARS-CoV-2 in Indonesia,ASEAN and the Neighbouring East Asian Countries: Features,Challenges and Achievements

Whole-genome sequencing (WGS) has played a significant role in understanding the epidemiology and biology of SARS-CoV-2 virus. Here, we investigate the use of SARS-CoV-2 WGS in Southeast and East Asian countries as a genomic surveillance during the COVID-19 pandemic. Nottingham–Indonesia Collaboration for Clinical Research and Training (NICCRAT) initiative has facilitated collaboration between the University of Nottingham and a team in the Research Center for Biotechnology, National Research and Innovation Agency (BRIN), to carry out a small number of SARS-CoV-2 WGS in Indonesia using Oxford Nanopore Technology (ONT). Analyses of SARS- CoV-2 genomes deposited on GISAID reveal the importance of clinical and demographic metadata collection and the importance of open access and data sharing. Lineage and phylogenetic analyses of two periods defined by the Delta variant outbreak reveal that: (1) B.1.466.2 variants were the most predominant in Indonesia before the Delta variant outbreak, having a unique spike gene mutation N439K at more than 98% frequency, (2) Delta variants AY.23 sub-lineage took over after June 2021, and (3) the highest rate of virus transmissions between Indonesia and other countries was through interactions with Singapore and Japan, two neighbouring countries with a high degree of access and travels to and from Indonesia.     

Highly Thermotolerant SARS-CoV-2 Vaccine Elicits Neutralising Antibodies against Delta and Omicron in Mice

As existing vaccines fail to completely prevent COVID-19 infections or community transmission, there is an unmet need for vaccines that can better combat SARS-CoV-2 variants of concern (VOC). We previously developed highly thermo-tolerant monomeric and trimeric receptor-binding domain derivatives that can withstand 100 °C for 90 min and 37 °C for four weeks and help eliminate cold-chain requirements. We show that mice immunised with these vaccine formulations elicit high titres of antibodies that neutralise SARS-CoV-2 variants VIC31 (with Spike: D614G mutation), Delta and Omicron (BA.1.1) VOC. Compared to VIC31, there was an average 14.4-fold reduction in neutralisation against BA.1.1 for the three monomeric antigen-adjuvant combinations and a 16.5-fold reduction for the three trimeric antigen-adjuvant combinations; the corresponding values against Delta were 2.5 and 3.0. Our findings suggest that monomeric formulations are suitable for upcoming Phase I human clinical trials and that there is potential for increasing the efficacy with vaccine matching to improve the responses against emerging variants. These findings are consistent with in silico modelling and AlphaFold predictions, which show that, while oligomeric presentation can be generally beneficial, it can make important epitopes inaccessible and also carries the risk of eliciting unwanted antibodies against the oligomerisation domain.     

Neutrophil/platelet to lymphocyte ratio in monitoring of response to TNF‐α inhibitors in psoriatic patients

Neutrophil or platelet to lymphocyte ratio (NLR and PLR) has been proposed to be used as prognostic purposes in a variety of diseases. The aim of this study was to evaluate the usefulness of these ratios in monitoring of response to TNF‐α‐inhibitors in psoriatic patients. Eighty psoriatic patients were included and treated with TNF‐α‐inhibitors for 12 months based on drug protocol. Hematologic indices, including NLR and PLR values were assessed before and after treatment. Data on psoriasis area and severity index (PASI), smoking behavior, alcohol intake habit, nail abnormality, body mass index (BMI), joint involvement, and disease duration were also recorded. PASI scores were improved significantly after one‐year treatment (P = .000). Furthermore, this type of treatment significantly reduced the NLR and PLR (P = .000). These changes were in accordance with PASI scores. Patients with BMI greater than 24.9 had higher, but non‐significant NLR and PLR than normal or lean individuals. Cigarette smokers and alcohol consumers had lower NLR and PLR values than other individuals (P < .05). There was no significant association between NLR and PLR and joint or nail involvement. Although NLR and PLR will not be helpful in primary diagnosis of inflammatory diseases, they could be accounted as monitoring tools in management of psoriasis or globally indicators of inflammation.     

Shortfalls in published neurosurgical literature

Expenditure related to neurosurgery has increased unevenly since the early 1990s. In this study we explored the literature by which clinical evidence is obtained to better direct neurosurgical practice. We searched different types of neurosurgery literature and four major neurosurgical procedures (excision of brain lesion, cerebral aneurysm clipping/coiling, discectomy, spine fusion) written in English on PubMed from 1996, the year of its launch, using the keyword "cost". Only a small and static portion of the neurosurgical literature was indexed as level I clinical evidence (randomized controlled trials), with a lack of cost appraisal in the outcome analysis of neurosurgical interventions. By way of rectification, a major increase in funding of grade I studies with cost analysis, and the requirement by peer-reviewed journals of a cost-benefit analysis, would promote the quality of clinical research yielding unquestionable advantage on national healthcare practice.     

Prevalence of Suicide Thoughts,Plans and Attempts in a Community Sample from Karaj,Iran

Aim of this study was to evaluate the prevalence of suicide ideation and behavior in a community sample of an Iranian city, Karaj. Study sample consisted of 2,300 subjects, chosen randomly from the community. The WHO/SUPRE-MISS survey questionnaire, used in this study. Lifetime prevalence for suicide thoughts, plans and attempts were 12.7, 6.2 and 3.3%, respectively and for the previous year they were 5.7, 2.9 and 1%, respectively. Although it is not possible to generalize the results to the country, but in some area of Iran, the prevalence of suicide ideation, plan and attempt appeared to be similar to that of many developed countries.     

Characterization of a potent inhibitor of platelet aggregation and release reaction isolated from allium sativum (garlic)

When added to platelet-rich plasma, aqueous extracts of garlic inhibited platelet aggregation and the release reaction. Subsequent experiments designed to characterize the inhibitory component revealed that the inhibitory activity was i) associated with small molecular-weight components, ii) the inhibitory component possessed the typical garlic odor and contained an abundance of sulfur, iii) the inhibitory activity could be extracted with organic solvents, and iv) temperatures above 56 degrees C and alkaline pH above 8.5 quickly destroyed the inhibitory activity. The Rf value of the major inhibitory component after thin-layer chromatographic separation was similar to that of allicin, an unique thiosulfinate in garlic previously shown to possess strong antibiotic and antifungal properties. Allicin was synthesized. On thin-layer chromatographic plates, allicin co-migrated with the inhibitory component in garlic. At 10 microM concentration, allicin inhibited completely platelet aggregation and the release reaction. Comparative studies suggest that the major platelet aggregation and release inhibitor in garlic may be allicin.     

Preparation of NiFe2O4@MIL-101(Fe)/GO as a novel nanocarrier and investigation of its antimicrobial properties

In this research, we have investigated a novel magnetic nanocomposite including NiFe₂O₄@MIL-101(Fe)/GO for the delivery of the antibiotic tetracycline (TC). Moreover, the antibacterial activity of NiFe₂O₄@MIL-101(Fe)/GO, NiFe₂O₄@MIL-101(Fe)/GO/TC and pure TC was evaluated by agar well diffusion and minimum inhibitory concentration (MIC) methods on both Gram-negative (Escherichia coli) and Gram-positive (Staphylococcus aureus) bacteria. In addition, the cytotoxicity of NiFe₂O₄@MIL-101(Fe)/GO/TC on HeLa cells was determined by an MTT assay which showed good results. The structure of the prepared nanocarrier was investigated by various spectroscopic techniques such as Fourier-transform infrared spectroscopy (FT-IR), energy-dispersive X-ray spectroscopy (EDX), X-ray diffraction (XRD), field emission scanning electron microscopy (FE-SEM), Brunauer–Emmett–Teller (BET), and thermal gravimetric analysis (TGA). The results of this study showed that 98% of the TC was loaded on the synthesized nanocomposite. Drug release occurred at pH: 7.4 (phosphate buffer saline) and pH: 5.0 (acetate buffer) within 3 days, resulting in 77% and 85% release of the drug, respectively.

A schematic exhibition of the synthetic procedure of NiFe₂O₄@MIL-101(Fe)/GO as TC carrier and antibacterial activities.