Neutrophil-lymphocyte ratio in Guillain-Barré syndrome: A prognostic biomarker of severe disease and mechanical ventilation in Bangladesh.

In addition to cellular and humoral immunity, inflammatory markers play an important role in the pathogenesis of Guillain-Barré syndrome (GBS) and are used to predict prognosis in many autoimmune diseases. The aim of this study was to identify whether the neutrophil-lymphocyte ratio (NLR), platelet-lymphocyte ratio, and monocyte-lymphocyte ratio in the early stages of GBS have prognostic value for severe disease, mechanical ventilation (MV) and poor long-term outcome. A prospective cohort study of 140 adult patients with GBS and 140 healthy controls (HC) was performed in Bangladesh during 2019-2022. Clinicodemographic characteristics of the patients were recorded, and hematological parameters were measured using an automated hematology analyzer. Median patient age was 35 (44-23) years; 71% were male; 88% were severely affected (GBS Disability Score> 3); 32% required MV. Patients had higher NLR than HC (P< .0001). Among patients, elevated NLR was associated with severe GBS and MV (P= .001 and <.0001, respectively) and moderately positively correlated with poor outcomes at 4 weeks (r = 0.423). Multiple logistic regression revealed NLR was an independent risk factor for severe GBS (OR = 5.2, 95% CI = 1.6-17.4) and MV (OR = 1.5 1.1-2.1). No significant association was observed between elevated NLR and the long-term outcome of GBS. Receiver operating characteristic curves revealed NLR cut-off values of ≥ 2.432 and ≥ 4.4423 predicted severe disease (sensitivity = 71%, specificity = 75%, AUC = 0.750, 95% CI = 0.651-0.849, P = .001) and MV (sensitivity = 65.9%, specificity = 81.7%, AUC = 0.804, 95% CI=0.724-0.884; P< .001). The NLR in the early stage of GBS may represent an independent prognostic factor of severe GBS and the requirement for MV.

High resolution melting curve analysis targeting the HBB gene mutational hot-spot offers a reliable screening approach for all common as well as most of the rare beta-globin gene mutations in Bangladesh.

BACKGROUND: Bangladesh lies in the global thalassemia belt, which has a defined mutational hot-spot in the beta-globin gene. The high carrier frequencies of beta-thalassemia trait and hemoglobin E-trait in Bangladesh necessitate a reliable DNA-based carrier screening approach that could supplement the use of hematological and electrophoretic indices to overcome the barriers of carrier screening. With this view in mind, the study aimed to establish a high resolution melting (HRM) curve-based rapid and reliable mutation screening method targeting the mutational hot-spot of South Asian and Southeast Asian countries that encompasses exon-1 (c.1 - c.92), intron-1 (c.92 + 1 - c.92 + 130) and a portion of exon-2 (c.93 - c.217) of the HBB gene which harbors more than 95% of mutant alleles responsible for beta-thalassemia in Bangladesh. RESULTS: Our HRM approach could successfully differentiate ten beta-globin gene mutations, namely c.79G > A, c.92 + 5G > C, c.126_129delCTTT, c.27_28insG, c.46delT, c.47G > A, c.92G > C, c.92 + 130G > C, c.126delC and c.135delC in heterozygous states from the wild type alleles, implying the significance of the approach for carrier screening as the first three of these mutations account for ~85% of total mutant alleles in Bangladesh. Moreover, different combinations of compound heterozygous mutations were found to generate melt curves that were distinct from the wild type alleles and from one another. Based on the findings, sixteen reference samples were run in parallel to 41 unknown specimens to perform direct genotyping of the beta-thalassemia specimens using HRM. The HRM-based genotyping of the unknown specimens showed 100% consistency with the sequencing result. CONCLUSIONS: Targeting the mutational hot-spot, the HRM approach could be successfully applied for screening of beta-thalassemia carriers in Bangladesh as well as in other countries of South Asia and Southeast Asia. The approach could be a useful supplement of hematological and electrophortic indices in order to avoid false positive and false negative results.

Medical Abortion Provision by Pharmacies and Drug Sellers in Low- and Middle-Income Countries: A Systematic Review.

We undertook a systematic review to assess 1) the level and quality of pharmacy and drug shop provision of medical abortion (MA) in low- and middle-income countries (LMICs) and 2) interventions to improve quality of provision. We used standardized terms to search six databases for peer-reviewed and grey literature. We double-extracted data using a standardized template, and double-graded studies for methodological quality. We identified 22 studies from 16 countries reporting on level and quality of MA provision through pharmacies and drug sellers, and three intervention studies. Despite widespread awareness and provision of MA drugs, even in legally restricted contexts, most studies found that pharmacy workers and drug sellers had poor knowledge of effective regimens. Evidence on interventions to improve pharmacy and drug shop provision of MA was limited and generally low quality, but indicated that training could be effective in improving knowledge. Programmatic attention should focus on the development and rigorous evaluation of innovative interventions to improve women's access to information about MA self-management in low-and middle-income countries.

Processing of semolina, a wonder resource for resistant starch production: In vitro digestibility and biochemical evaluation.

With the advent of modern technology, the utilization of residues obtained after food processing are being largely explored for commercialization. Semolina, a starch rich food ingredient is one of such byproducts of food processing that has not been yet vividly studied, although it is profusely used as an important ingredient in Indian cuisines. Rapid digestibility of most starch rich foods boosts up the blood glucose level. Thus, the present study put forward an attempt to curtail the rapid digestibility of starch rich semolina flour by increasing its resistant starch content through enzymatic process. The enzymatically modified semolina flour (MS) was compared with its native counterpart (NS) on grounds of their digestibility pattern, biochemical and functional properties. A rise in resistant starch content by 9.3 ± 1.6 %, amylose content by 10.9 ± 1.2 %, crystallinity by 10.4 % and the drop in readily digestible starch by 11.9 ± 1.4 % and oil absorption by 2.1 ± 0.3 g/g were observed in MS. These initial findings of the present study are interesting as the results showed elevated potential of the modified semolina flour to be used as functional ingredient in cuisines worldwide.

Strengthening individual and family resilience against leprosy-related discrimination: A pilot intervention study.

BACKGROUND: Leprosy and leprosy-related stigma can have a major impact on psychosocial wellbeing of persons affected and their family members. Resilience is a process that incorporates many of the core skills and abilities which may enable people to address stigma and discrimination. The current study aimed to develop and pilot an intervention to strengthen individual and family resilience against leprosy-related discrimination. METHODOLOGY: We used a quasi-experimental, before-after study design with a mixed methods approach. The 10-week family-based intervention was designed to strengthen the resilience of individuals and families by enhancing their protective abilities and capacity to overcome adversity. The study was conducted in two sites, urban areas in Telangana state, and in rural areas in Odisha state, India. Persons affected and their family members were included using purposive sampling. Two questionnaires were used pre-and post-intervention: the Connor-Davidson Resilience Scale (CD-RISC, maximum score 100, with high scores reflecting greater resilience) and the WHOQOL-BREF (maximum score of 130, with higher scores reflecting higher quality of life). In addition, semi-structured interviews were conducted post-intervention. Data were collected at baseline, a few weeks after completion of the intervention, and in the Odisha cohort again at six months after completion. Paired t-tests measured differences pre- and post- intervention. Qualitative data were thematically analysed. FINDINGS: Eighty participants across 20 families were included in the study (23 persons affected and 57 family members). We found a significant increase in CD-RISC scores for persons affected and family members from Odisha state (baseline 46.5, first follow-up 77.0, second follow-up 70.0), this improvement was maintained at six-month follow-up. There was no increase in CD-RISC scores post-intervention among participants from Telangana state. WHOQOL-BREF scores were significantly higher at follow-up for persons affected in both states, and for family members in Odisha state. No families dropped out of the study. In the qualitative feedback, all participants described drawing benefit from the programme. Participants especially appreciated the social dimensions of the intervention. CONCLUSION: This pilot study showed that the 10-week family-based intervention to strengthen resilience among persons affected by leprosy and their family members was feasible, and has the potential to improve resilience and quality of life. A large-scale efficacy trial is necessary to determine the effectiveness and long-term sustainability of the intervention.

Enzyme mediated resistant starch production from Indian Fox Nut (Euryale ferox) and studies on digestibility and functional properties.

Starch rich foods are almost indispensable in mundane diet of people round the globe. Rapid digestibility of starch culminates into elevated blood glucose level which is an evident factor for many diseases. To curb this rapid digestibility and the elevated glycemic response, resistant starch content in highly nutritious but unexplored popped makhana (Euryale ferox) was increased by amylopullulanase treatment. In the present study, amylopullulanase treated makhana flour (MM) was compared with the native makhana flour (NM) based on physicochemical and functional properties, where enhanced amylose content, resistant starch and crystallinity were recorded to be 12.33 %, 14.88 % and 11.32 % respectively, whereas, readily digestible starch and oil holding capacity decreased by 13.01 % and 3.12 g/g respectively. The present study ensures the reduction and sustainable release of glucose during in vitro digestibility analysis. These findings point out the elevated potential of amylopullulanase treated makhana flour for therapeutic food formulation.

Gliotoxin, identified from a screen of fungal metabolites, disrupts 7SK snRNP, releases P-TEFb, and reverses HIV-1 latency.

A leading pharmacological strategy toward HIV cure requires "shock" or activation of HIV gene expression in latently infected cells with latency reversal agents (LRAs) followed by their subsequent clearance. In a screen for novel LRAs, we used fungal secondary metabolites as a source of bioactive molecules. Using orthogonal mass spectrometry (MS) coupled to latency reversal bioassays, we identified gliotoxin (GTX) as a novel LRA. GTX significantly induced HIV-1 gene expression in latent ex vivo infected primary cells and in CD4+ T cells from all aviremic HIV-1+ participants. RNA sequencing identified 7SK RNA, the scaffold of the positive transcription elongation factor b (P-TEFb) inhibitory 7SK small nuclear ribonucleoprotein (snRNP) complex, to be significantly reduced upon GTX treatment of CD4+ T cells. GTX directly disrupted 7SK snRNP by targeting La-related protein 7 (LARP7), releasing active P-TEFb, which phosphorylated RNA polymerase II (Pol II) C-terminal domain (CTD), inducing HIV transcription.