Expression Pattern of Selected Toll-like Receptors (TLR's) in the PBMC's of Severe and Non-severe Dengue Cases.

Objective: The role of TLR's in the pathogenesis of dengue is not explored well. Differential expression of TLR2 and TLR4 was reported in dengue cases. In the present study in order to understand the expression pattern of various TLR's, including TLR2, TLR3, TLR4 and TLR9, mRNA levels were determined in various dengue study groups compared to control groups, at the time of admission and around defervescence using quantitative real-time PCR (RT-PCR).Methods: A total of 88 dengue cases with 32 severe and 56 non-severe cases were involved in the study. Gene expression pattern of the study groups was compared with 31 other febrile illness (OFI) cases and 63 healthy controls. Transcript levels of the target genes were estimated from the peripheral blood mononuclear cells (PBMC) samples collected from cases and controls using quantitative real-time PCR.Results: We have noted a significant alteration in the levels of all TLR's in dengue and OFI cases compared to healthy controls at the time of admission. Interestingly we have noted a significant alteration in the levels of TLR9 in severe and non-severe cases during defervescence. The same was not detected in the OFI group.Conclusion: The present study found a change in TLR's during dengue infection. This suggests us to explore the TLR's as therapeutic candidate for anti-dengue virus strategies. However, in order to ascertain the involvement of TLR's in the disease pathology and its role as biomarkers for prognosis, a complete dynamics of TLR's expression needs to be studied.

Altered Platelet Fatty Acids in Dengue Cases by Gas Chromatography-Mass Spectrometry Analysis.

BACKGROUND: The role of dengue virus in altering the functional properties of platelets remains poorly understood. Few studies have observed that changes in fatty acids are found to have an effect on platelet activation and aggregation. Also, platelet fatty acids have not been extensively studied in dengue so far. So, we aimed to study the fatty acids of platelet membranes in patients with dengue. METHODS: Gas chromatography-mass spectrometry (GC-MS) method was used to analyze fatty acids in the lipid extracts of platelets isolated from the study participants. RESULTS: GC-MS analysis of platelet lipids identified and quantified nearly 23 unique lipid molecules on platelet membrane. We observed significant alterations with some of the fatty acids in patients with dengue compared to controls. Within dengue cases, increase in unsaturated fatty acids in severe dengue was observed compared to non-severe dengue. From baseline to defervescence, no difference in fatty acids was observed in dengue platelets. This indicates that in dengue, platelet physiology remains altered even after the febrile phase. CONCLUSION: To the best of our knowledge, this is the first study characterizing the differential expression of platelet fatty acids in dengue infection. However, further studies are warranted to expound the underlying cause for thrombocytopenia and platelet dysfunction in dengue.

Effect of Curcuma longa on vascular function in native Tamilians with type 2 diabetes mellitus: A randomized, double-blind, parallel arm, placebo-controlled trial.

Diabetes mellitus is characterized by increased central arterial stiffness and endothelial dysfunction leading to increased risk of cardiovascular complications. The aim of this study is to evaluate the effect of Curcuma longa on arterial stiffness and endothelial dysfunction in patients with type 2 diabetes mellitus. This randomized controlled trial was conducted in 136 patients of type 2 diabetes. Among them, 114 completed at least one follow-up visit and included for data analysis. Arterial stiffness parameters were measured at baseline and every month for 3 months and endothelial dysfunction markers at baseline and after 3 months of treatment with C. longa or placebo. These parameters were compared between the two groups. Both C. longa and placebo groups were comparable at baseline. After 3 months of treatment, C. longa produced significant reduction from baseline in carotid-femoral pulse wave velocity (p = .002), left brachial-ankle pulse wave velocity (p = .001), aortic augmentation pressure (p = .007), aortic augmentation index (p = .007), and aortic augmentation index at heart rate 75 (p = .018) as compared with the placebo group. Three months treatment with C. longa significantly decreases arterial stiffness as compared with placebo in type 2 diabetes mellitus patients.

A Study on Gene Expression Profile of Endogenous Antioxidant Enzymes: CAT, MnSOD and GPx in Dengue Patients.

Dengue is an arthropod-borne threat among tropical countries. Currently no effective means to treat the virus or to predict which patient will develop the severe form of the disease. Recently the relationship between oxidative/antioxidative response and dengue pathogenesis was suggested. Based on this the present study has analysed the expression of endogenous antioxidant genes: Catalase (CAT), Superoxide dismutase (MnSOD) and Glutathione peroxidase in patients with dengue compared to other febrile illness (OFI) and healthy controls. The study enrolled 88 dengue confirmed patients comprising 56 were patients with non-severe dengue, and 32 were severe dengue cases, 31 were patients with OFI, and 63 healthy controls were also involved. Peripheral blood mononuclear cells isolated from patients and controls during the day of admission and from the available cases on the day of defervescence were used to estimate the transcript levels by quantitative PCR. The expression levels of all the three genes were found to be down-regulated throughout the course of dengue infection (p < 0.05) and OFI cases compared to healthy controls. Within dengue group, no significant difference was observed in any of the parameters between severe and non-severe cases. Interestingly, a significant down-regulation of MnSOD expression was recorded in secondary dengue infection compared to primary during admission (p < 0.05). It was found that all the down-regulated study genes have positively correlated in all dengue cases during the day of admission (p < 0.01). But during defervescence, the same was found only between CAT and MnSOD. Down-regulated endogenous antioxidant enzymes during dengue infection could be the possible rationale of oxidative stress reported in dengue disease earlier. The present study markers could not distinguish dengue from OFI cases and severe from non-severe dengue cases. Mechanism of down-regulation has to be explored further which will pave the way for the therapeutic target in dengue disease.

Carbohydrate Deficient Transferrin and Interleukin-6 as Predictors of Fibrosis in Alcohol Cirrhosis.

The severity of alcoholic cirrhosis depends on the presence of liver inflammation and fibrogenesis. Previous studies have hypothesized that carbohydrate deficient transferrin can be used as marker of liver impairment in alcoholic liver disease patients. The present study was designed to assess whether carbohydrate deficient transferrin is associated with procollagen III peptide and predict fibrosis in alcohol cirrhosis patients. We enrolled 48 patients with alcoholic cirrhosis and 38 healthy controls. Serum carbohydrate deficient transferrin, procollagen III peptide and interleukin-6 levels were estimated in both groups. Serum carbohydrate deficient transferrin, procollagen III peptide and interleukin-6 were significantly increased in alcoholic cirrhosis patients compared to controls. Stepwise regression analysis showed that carbohydrate deficient transferrin (adjusted R(2) = 0.313, ß = 0.362, p = 0.003) and interleukin-6 (adjusted R(2) = 0.194, ß = 0.459, p = 0.001) were positively associated with procollagen III peptide when age, duration and amount of alcohol consumption were considered as covariates. We conclude that elevated carbohydrate deficient transferrin and interleukin-6 act as predictors of fibrosis in alcoholic cirrhosis.

CPAP for the metabolic syndrome in patients with obstructive sleep apnea.

BACKGROUND: Obstructive sleep apnea is associated with an increased prevalence of the metabolic syndrome and its components. It is unclear whether treatment of obstructive sleep apnea syndrome with continuous positive airway pressure (CPAP) would modify these outcomes. METHODS: In our double-blind, placebo-controlled trial, we randomly assigned patients with obstructive sleep apnea syndrome to undergo 3 months of therapeutic CPAP followed by 3 months of sham CPAP, or vice versa, with a washout period of 1 month in between. Before and after each intervention, we obtained measurements of anthropometric variables, blood pressure, fasting blood glucose levels, insulin resistance (with the use of homeostasis model assessment), fasting blood lipid profile, glycated hemoglobin levels, carotid intima-media thickness, and visceral fat. The metabolic syndrome was defined according to National Cholesterol Education Program Adult Treatment Panel III criteria, with Asian cutoff values for abdominal obesity. RESULTS: A total of 86 patients completed the study, 75 (87%) of whom had the metabolic syndrome. CPAP treatment (vs. sham CPAP) was associated with significant mean decreases in systolic blood pressure (3.9 mm Hg; 95% confidence interval [CI], 1.4 to 6.4; P=0.001), diastolic blood pressure (2.5 mm Hg; 95% CI, 0.9 to 4.1; P<0.001), serum total cholesterol (13.3 mg per deciliter; 95% CI, 5.3 to 21.3; P=0.005), non-high-density lipoprotein cholesterol (13.3 mg per deciliter; 95% CI, 4.8 to 21.8; P=0.009), low-density lipoprotein cholesterol (9.6 mg per deciliter; 95% CI, 2.5 to 16.7; P=0.008), triglycerides (18.7 mg per deciliter; 95% CI, 4.3 to 41.6; P=0.02), and glycated hemoglobin (0.2%; 95% CI, 0.1 to 0.4; P=0.003). The frequency of the metabolic syndrome was reduced after CPAP therapy (reversal found in 11 of 86 patients [13%] undergoing CPAP therapy vs. 1 of 86 [1%] undergoing sham CPAP). Accelerated hypertension developed 1 patient receiving CPAP therapy first, intolerance to CPAP developed in 2 others, and another patient declined to continue sham CPAP. CONCLUSIONS: In patients with moderate-to-severe obstructive sleep apnea syndrome, 3 months of CPAP therapy lowers blood pressure and partially reverses metabolic abnormalities. (Funded by Pfizer; ClinicalTrials.gov number, NCT00694616.).

Adiponectin-resistin index and its strong association with acute coronary syndrome in South Indian men.

BACKGROUND: India has the highest burden of acute coronary syndromes worldwide. Apart from certain lipid alterations that have been established to be definite risk factors, low level of adiponectin, high levels of resistin, and IL-6 have been shown to be risk factors for cardiovascular events. Insulin resistance is also a significant predictor of poor outcome in patients admitted with ACS. METHODS: 69 male patients with ACS and 70 age-matched healthy males were recruited in the study. Insulin, total adiponectin, resistin, and IL-6 levels were assayed in all study subjects. Indices of insulin resistance and novel adipokine indices were calculated using standard formulae. Multiple logistic regression analysis was done to find out the best predictor of ACS. RESULTS: Resistin, IL-6, insulin resistance indices, AR index, and IRAR index were found to be significantly higher, while insulin sensitivity indices and total adiponectin were found to be lower in cases, as compared with controls (p < 0.001). Insulin resistance was found to be higher in the admission sample, when compared to the fasting sample in patients with ACS (p = 0.01). On multivariate logistic regression analysis, HOMA-IR and AR index were found to be significantly associated with ACS. AR index was the best independent predictor of ACS, with the highest odds ratio (AR index: adjusted OR 17.528, p < 0.0001 versus HOMA-IR: adjusted OR 1.146, p = 0.001). CONCLUSIONS: The present results implicate that adipokines are significantly associated with pathogenesis of ACS, warranting adequate and early appropriate treatment to reverse this metabolic dysregulation. In our study, AR index was the best predictor of ACS. Hence, the novel AR index might be useful in routine clinical practice for screening persons with increased risk of future development of ACS.

Validation of the megakaryocyte fragmentation theory of finger clubbing in patients with cardiopulmonary diseases.

Dickinson and Martin had proposed that finger clubbing is caused by distal impaction of large-sized platelets that escape physiological fragmentation in lung vasculature. Empirical evidence to support this theory, however, is limited and conflicting. Moreover, this theory has not been verified in patients with lung diseases. We conducted a cross-sectional analytic study to validate the megakaryocyte fragmentation theory in patients with cardiopulmonary diseases. We studied four groups - patients with cyanotic heart diseases and clubbing (n = 20); patients with non-malignant lung diseases and clubbing (n = 25); patients with non-malignant lung diseases but no clubbing (n = 25); and healthy individuals (n = 25). We measured the distal phalangeal depth ratio, estimated the platelet volume indices, and examined the peripheral blood smear for the presence of large platelets. We found that patients with clubbing due to cyanotic heart diseases had a significantly lower platelet count (median [IQR] 201 [157-241] vs. 303 [258-334] × 10(3)/µl; p < 0.001), higher platelet volume (mean difference, Δ [95% CI] = 0.93 fl [0.37-1.49 fl]; p = 0.002) and platelet large cell ratio (Δ = 7.99% [3.71%-12.26%]; p < 0.001) as compared to healthy individuals. They were also significantly more likely to have large platelets on peripheral blood smear as compared to healthy individuals (9/25 vs. 0/25; p = 0.002). However, in patients with lung diseases, irrespective of the presence or absence of clubbing, platelet count and platelet volume indices were not different from healthy individuals. Our findings support the megakaryocyte fragmentation theory of finger clubbing in patients with cyanotic heart diseases. However, this theory does not explain the clubbing seen in non-malignant lung diseases.

Rifamycins (rifampicin, rifabutin and rifapentine) compared to isoniazid for preventing tuberculosis in HIV-negative people at risk of active TB.

BACKGROUND: Preventing active tuberculosis (TB) from developing in people with latent tuberculosis infection (LTBI) is important for global TB control. Isoniazid (INH) for six to nine months has 60% to 90% protective efficacy, but the treatment period is long, liver toxicity is a problem, and completion rates outside trials are only around 50%. Rifampicin or rifamycin-combination treatments are shorter and may result in higher completion rates. OBJECTIVES: To compare the effects of rifampicin monotherapy or rifamycin-combination therapy versus INH monotherapy for preventing active TB in HIV-negative people at risk of developing active TB. SEARCH METHODS: We searched the Cochrane Infectious Disease Group Specialized Register; Cochrane Central Register of Controlled Trials (CENTRAL); MEDLINE; EMBASE; LILACS; clinical trials registries; regional databases; conference proceedings; and references, without language restrictions to December 2012; and contacted experts for relevant published, unpublished and ongoing trials. SELECTION CRITERIA: Randomized controlled trials (RCTs) of HIV-negative adults and children at risk of active TB treated with rifampicin, or rifamycin-combination therapy with or without INH (any dose or duration), compared with INH for six to nine months. DATA COLLECTION AND ANALYSIS: At least two authors independently screened and selected trials, assessed risk of bias, and extracted data. We sought clarifications from trial authors. We pooled relative risks (RRs) with their 95% confidence intervals (CIs), using a random-effects model if heterogeneity was significant. We assessed overall evidence quality using the GRADE approach. MAIN RESULTS: Ten trials are included, enrolling 10,717 adults and children, mostly HIV-negative (2% HIV-positive), with a follow-up period ranging from two to five years. Rifampicin (three/four months) vs. INH (six months)Five trials published between 1992 to 2012 compared these regimens, and one small 1992 trial in adults with silicosis did not detect a difference in the occurrence of TB over five years of follow up (one trial, 312 participants; very low quality evidence). However, more people in these trials completed the shorter course (RR 1.19, 95% CI 1.01 to 1.30; five trials, 1768 participants; moderate quality evidence). Treatment-limiting adverse events were not significantly different (four trials, 1674 participants; very low quality evidence), but rifampicin caused less hepatotoxicity (RR 0.12, 95% CI 0.05 to 0.30; four trials, 1674 participants; moderate quality evidence). Rifampicin plus INH (three months) vs. INH (six months)The 1992 silicosis trial did not detect a difference between people receiving rifampicin plus INH compared to INH alone for occurrence of active TB (one trial, 328 participants; very low quality evidence). Adherence was similar in this and a 1998 trial in people without silicosis (two trials, 524 participants; high quality evidence). No difference was detected for treatment-limiting adverse events (two trials, 536 participants; low quality evidence), or hepatotoxicity (two trials, 536 participants; low quality evidence). Rifampicin plus pyrazinamide (two months) vs. INH (six months)Three small trials published in 1994, 2003, and 2005 compared these two regimens, and two reported a low occurrence of active TB, with no statistically significant differences between treatment regimens (two trials, 176 participants; very low quality evidence) though, apart from one child from the 1994 trial, these data on active TB were from the 2003 trial in adults with silicosis. Adherence with both regimens was low with no statistically significant differences (four trials, 700 participants; very low quality evidence). However, people receiving rifampicin plus pyrazinamide had more treatment-limiting adverse events (RR 3.61, 95% CI 1.82 to 7.19; two trials, 368 participants; high quality evidence), and hepatotoxicity (RR 4.59, 95% 2.14 to 9.85; three trials, 540 participants; moderate quality evidence). Weekly, directly-observed rifapentine plus INH (three months) vs. daily, self-administered INH (nine months)A large trial conducted from 2001 to 2008 among close contacts of TB in the USA, Canada, Brazil and Spain found directly observed weekly treatment to be non-inferior to nine months self-administered INH for the incidence of active TB (0.2% vs 0.4%, RR 0.44, 95% CI 0.18 to 1.07, one trial, 7731 participants; moderate quality evidence). The directly-observed, shorter regimen had higher treatment completion (82% vs 69%, RR 1.19, 95% CI 1.16 to 1.22, moderate quality evidence), and less hepatotoxicity (0.4% versus 2.4%; RR 0.16, 95% CI 0.10 to 0.27; high quality evidence), though treatment-limiting adverse events were more frequent (4.9% versus 3.7%; RR 1.32, 95% CI 1.07 to 1.64 moderate quality evidence) AUTHORS' CONCLUSIONS: Trials to date of shortened prophylactic regimens using rifampicin alone have not demonstrated higher rates of active TB when compared to longer regimens with INH. Treatment completion is probably higher and adverse events may be fewer with shorter rifampicin regimens. Shortened regimens of rifampicin with INH may offer no advantage over longer INH regimens. Rifampicin combined with pyrazinamide is associated with more adverse events. A weekly regimen of rifapentine plus INH has higher completion rates, and less liver toxicity, though treatment discontinuation due to adverse events is probably more likely than with INH.

Clinical Profile and Predictors of Mortality among Patients with Melioidosis.

Introduction: Melioidosis is an under-recognized but important infection with high mortality and morbidity. It is endemic along the coastal regions of the Southern part of India. The present study focuses on the varied clinical manifestations, associated risk factors, and outcomes in patients from the Southeastern part of India. Methods: Seventy patients from January 2018 to June 2021 from a Tertiary Care Hospital were included and prospectively followed up from 6 months to 3 years. Cox regression was performed to test for the association of various clinical and demographic factors with overall survival. Results: Diabetes and occupational exposure to soil and water (78.6%) followed by alcoholism (61.4%) were the most common risk factors for melioidosis. The most frequent presentation was sepsis (47.1%), followed by skin and soft tissue infection (32.9%) and pneumonia (25.7%). Mortality was 50%. Patients with sepsis had a 3.5-fold higher risk of mortality (adjusted hazard ratio = 3.50; P = 0.01) while other risk factors were not significantly associated with mortality. Conclusion: Lifestyle-dependent risk factors (diabetes, occupational exposure, and alcoholism) were most common among patients with melioidosis. Hospitalization among patients with sepsis is associated with high mortality despite the initiation of specific therapy.

Bacteriuria due to Typhoidal and Nontyphoidal Salmonella: A Report of Three Cases from South India.

Urinary tract infection (UTI) with Salmonella is uncommon, accounting for merely 0.01% to 0.1% of cases of UTIs. It is reported more frequently in the presence of predisposing factors such as structural abnormalities of the urinary tract or weakened immune system. We present a case series of three patients with Salmonella bacteriuria and their susceptibility patterns. All three patients had underlying urologic features such as neurogenic bladder, chronic kidney disease, and urethral stricture, and two presented with urinary tract involvement symptoms.

Transcriptomic and proteomic analyses of Mycobacterium tuberculosis strains isolated from tuberculous meningitis patients.

Background: Tuberculous meningitis (TBM) is caused by the dissemination of Mycobacterium tuberculosis (MTB) from the primary site of infection to the central nervous system. However, the bacterial factors associated with the pathogenesis of TBM remain unclear. This study employed transcriptomic and proteomic methods to comprehensively analyze the changes in genes and proteins and their associated pathways in MTB strains isolated from cerebrospinal fluid (CSF) of TBM and sputum of pulmonary TB (PTB) cases. Methodology: Five MTB strains were subjected to OMICs (transcriptomic and proteomic) analysis. Among five MTB strains, two were isolated from CSF and sputum samples of the same patient with PTB and TBM infections, one from the sputum of a different PTB patient, and a strain obtained from the CSF of another TBM patient. H37Rv was used as a reference strain. The reliability of transcriptomic results was validated by real time polymerase chain reaction with selected genes from 100 MTB isolates (CSF, 50 and sputum, 50). Results: The transcriptomic study revealed that overlapping differentially expressed genes of MTB strains isolated from TBM patients showed featured enrichment in benzoate degradation, lysine degradation, tryptophan metabolism, fatty acid degradation, ATP binding cassette transporters, microbial metabolism in diverse environments, biosynthesis of antibiotics, and metabolic pathways. Eleven genes were upregulated, and four were downregulated in MTB strains isolated from TBM compared to PTB. From proteomic analysis, we identified three candidate proteins belonging to plasminogen binding proteins (PBP) (enolase, dnaK, and isocitrate lyase 1) that were significantly upregulated in MTB strains isolated from TBM. Conclusion: Overall, the transcriptomic and proteomic analyses provided an important base for understanding the unique feature of TBM pathogenesis. To the best of our knowledge, this is the first report highlighting the importance of PBPs on TBM pathogenesis.

Safety and immunogenicity of SII-NVX-CoV2373 (COVID-19 vaccine) in adults in a phase 2/3, observer-blind, randomised, controlled study.

Background: NVX-CoV2373, a Covid-19 vaccine was developed in the USA with ∼90% efficacy. The same vaccine is manufactured in India after technology transfer (called as SII-NVX-CoV2373), was evaluated in this phase 2/3 immuno-bridging study. Methods: This was an observer-blind, randomised, phase 2/3 study in 1600 adults. In phase 2, 200 participants were randomized 3:1 to SII-NVX-CoV2373 or placebo. In phase 3, 1400 participants were randomized 3:1 to SII-NVX-CoV2373 or NVX-CoV2373 (940 safety cohort and 460 immunogenicity cohort). Two doses of study products (SII-NVX-CoV2373, NVX-CoV2373 or placebo) were given 3 weeks apart. Primary objectives were to demonstrate non-inferiority of SII-NVX-CoV2373 to NVX-CoV2373 in terms of geometric mean ELISA units (GMEU) ratio of anti-S IgG antibodies 14 days after the second dose (day 36) and to determine the incidence of causally related serious adverse events (SAEs) through 180 days after the first dose. Anti-S IgG response was assessed using an Enzyme-Linked Immunosorbent Assay (ELISA) and neutralizing antibodies (nAb) were assessed by a microneutralization assay using wild type SARS CoV-2 in participants from the immunogenicity cohort at baseline, day 22, day 36 and day 180. Cell mediated immune (CMI) response was assessed in a subset of 28 participants from immunogenicity cohort by ELISpot assay at baseline, day 36 and day 180. The total follow-up was for 6 months. Trial registration: CTRI/2021/02/031554. Findings: Total 1596 participants (200 in Phase 2 and 1396 in Phase 3) received the first dose. SII-NVX-CoV2373 was found non-inferior to NVX-CoV2373 (anti-S IgG antibodies GMEU ratio 0.91; 95% CI: 0.79, 1.06). At day 36, there was more than 58-fold rise in anti-S IgG and nAb titers compared to baseline in both the groups. On day 180 visit, these antibody titers declined to levels slightly lower than those after the first dose (13-22 fold-rise above baseline). Incidence of unsolicited and solicited AEs was similar between the SII-NVX-CoV2373 and NVX-CoV2373 groups. No adverse event of special interest (AESI) was reported. No causally related SAE was reported. Interpretation: SII-NVX-CoV2373 induced a non-inferior immune response compared to NVX-CoV2373 and has acceptable safety profile. Funding: SIIPL, Indian Council of Medical Research, Novavax.

A Panoramic View of Patients' Beliefs and Knowledge About Chronic Respiratory Disease.

Objective Patients with chronic respiratory diseases (CRD) like asthma and chronic obstructive pulmonary disease (COPD) experience significant morbidity and mortality. The patient's quality of life deteriorates with the progression of the disease. Pharmacological treatment focuses on reducing the symptoms. The psychological impact of the disease on the patient's quality of life is not assessed by all healthcare providers. There is limited knowledge about the patient's demographic and clinical factors affecting the quality of life in CRD patients and aspects hindering or influencing the management of disease in this population. Hence we aimed to conduct a qualitative study on patients with asthma or COPD to get a view of their knowledge about the disease, the problems they encounter in their day-to-day life and the treatment. Methods Semi-structured, face-to-face interviews were conducted by the investigator in the hospital during the patient's follow-up visits. The questions focused on the patient's awareness of the disease, living with chronic respiratory disease, understanding of disease and treatment, and compliance with inhaled therapy. The interviews were audio recorded and transcribed verbatim. Content analysis of the data was done manually. Codes and themes were derived manually. Themes were formed from the codes and sub-themes. Results Five themes were generated from the data obtained: (1) misconceptions regarding the contagious nature of the disease; (2) psychological stress due to feelings of worthlessness, helplessness due to inability to work and poor understanding among family members; (3) inappropriate lifestyle modifications like avoiding fruits and vegetables due to the fear of acute attacks; (4) poor adherence to inhalers due to work timing and difficulty travelling; and (5) lack of reinforcement by the healthcare providers on inhaler technique and adherence were identified as causes of poor inhaler technique and inappropriate knowledge about drugs. Conclusion Subjective reporting by patients in this study was helpful in understanding issues concerning disease management in CRD patients. Apart from assessing the patients' symptoms and prescribing drugs, healthcare providers should take time to impart knowledge about the disease to patients. Though patient education and psychological intervention are challenging to implement daily, they are supplemental to the pharmacologic management of the disease.

Estimation of seroprevalence of melioidosis among adult high risk groups in Southeastern India by indirect Hemagglutination assay.

Burkholderia pseudomallei is an environmental saprophyte known to cause melioidosis, a disease endemic in northern Australia and Southeast Asia. With the increasing number of melioidosis cases, there is a lack of data on seroprevalence rates and extent of exposure in high risk population of melioidosis from different endemic regions in India. The present cross sectional study was undertaken to estimate the seroprevalence of melioidosis in high risk populations in and around Puducherry, a coastal town in Southeastern India. Blood samples were collected from 275 diabetic individuals attending a tertiary care centre in Southern India and 275 farmers residing under the rural field practice area of our hospital. The antibody levels were estimated using an Indirect Hemagglutination Assay. The overall seropositivity was found to be 19.8% with a titer ≥1:20. Farmers were 2.8 times more likely to be seropositive than non-farmers. Rates of seroprevalence among diabetic subjects were less compared to the non-diabetic individuals. The seropositivity rates in non-diabetic farmers were higher (56/203, 27.6%) compared to diabetic farmers (34/164, 20.7%). The lowest seropositivity was seen among diabetic non-farmers at 10.4%. Multivariable logistic regression analysis revealed domicile (adjusted odds ratio-aOR: 2.32, 95% Confidence interval-CI: 1.05, 5.13) and contact with animals (aOR: 1.89, 95% CI:1.04, 3.44) as significant predictors of seropositivity. None of the other socio-demographic factors including gender and age were significantly associated with seropositivity. This study demonstrates widespread exposure to B. pseudomallei among adults residing in and around Puducherry, including those engaged in non-farming occupations.

Hyperglycemia and steroid use increase the risk of rhino-orbito-cerebral mucormycosis regardless of COVID-19 hospitalization: Case-control study, India.

BACKGROUND: In the ongoing COVID-19 pandemic, an increased incidence of ROCM was noted in India among those infected with COVID. We determined risk factors for rhino-orbito-cerebral mucormycosis (ROCM) post Coronavirus disease 2019 (COVID-19) among those never and ever hospitalized for COVID-19 separately through a multicentric, hospital-based, unmatched case-control study across India. METHODS: We defined cases and controls as those with and without post-COVID ROCM, respectively. We compared their socio-demographics, co-morbidities, steroid use, glycaemic status, and practices. We calculated crude and adjusted odds ratio (AOR) with 95% confidence intervals (CI) through logistic regression. The covariates with a p-value for crude OR of less than 0·20 were considered for the regression model. RESULTS: Among hospitalised, we recruited 267 cases and 256 controls and 116 cases and 231 controls among never hospitalised. Risk factors (AOR; 95% CI) for post-COVID ROCM among the hospitalised were age 45-59 years (2·1; 1·4 to 3·1), having diabetes mellitus (4·9; 3·4 to 7·1), elevated plasma glucose (6·4; 2·4 to 17·2), steroid use (3·2; 2 to 5·2) and frequent nasal washing (4·8; 1·4 to 17). Among those never hospitalised, age ≥ 60 years (6·6; 3·3 to 13·3), having diabetes mellitus (6·7; 3·8 to 11·6), elevated plasma glucose (13·7; 2·2 to 84), steroid use (9·8; 5·8 to 16·6), and cloth facemask use (2·6; 1·5 to 4·5) were associated with increased risk of post-COVID ROCM. CONCLUSIONS: Hyperglycemia, irrespective of having diabetes mellitus and steroid use, was associated with an increased risk of ROCM independent of COVID-19 hospitalisation. Rational steroid usage and glucose monitoring may reduce the risk of post-COVID.

Point-of-care infrared thermal imaging for differentiating venomous snakebites from non-venomous and dry bites.

BACKGROUND: Local envenomation following snakebites is accompanied by thermal changes, which could be visualized using infrared imaging. We explored whether infrared thermal imaging could be used to differentiate venomous snakebites from non-venomous and dry bites. METHODS: We prospectively enrolled adult patients with a history of snakebite in the past 24 hours presenting to the emergency of a teaching hospital in southern India. A standardized clinical evaluation for symptoms and signs of envenomation including 20-minute whole-blood clotting test and prothrombin time was performed to assess envenomation status. Infrared thermal imaging was done at enrolment, 6 hours, and 24 hours later using a smartphone-based device under ambient conditions. Processed infrared thermal images were independently interpreted twice by a reference rater and once by three novice raters. FINDINGS: We studied 89 patients; 60 (67%) of them were male. Median (IQR) time from bite to enrolment was 11 (6.5-15) hours; 21 (24%) patients were enrolled within 6 hours of snakebite. In all, 48 patients had local envenomation with/without systemic envenomation, and 35 patients were classified as non-venomous/dry bites. Envenomation status was unclear in six patients. At enrolment, area of increased temperature around the bite site (Hot spot) was evident on infrared thermal imaging in 45 of the 48 patients with envenomation, while hot spot was evident in only 6 of the 35 patients without envenomation. Presence of hot spot on baseline infrared thermal images had a sensitivity of 93.7% (95% CI 82.8% to 98.7%) and a specificity of 82.9% (66.3% to 93.4%) to differentiate envenomed patients from those without envenomation. Interrater agreement for identifying hot spots was more than substantial (Kappa statistic >0.85), and intrarater agreement was almost perfect (Kappa = 0.93). Paradoxical thermal changes were observed in 14 patients. CONCLUSIONS: Point-of-care infrared thermal imaging could be useful in the early identification of non-venomous and dry snakebites.

Diagnosis of Undifferentiated Connective Tissue Disease in a Patient With Digital Gangrene and Positive Antinuclear Antibodies.

The occurrence of ischemia of the digits or digital gangrene is a well-known complication of systemic autoimmune diseases, such as systemic sclerosis, systemic lupus erythematosus, and anti-phospholipid syndrome, among others. The pathophysiological mechanisms are small vessel vasculitis, vasospasm of Raynaud's phenomenon, microthrombi due to antiphospholipid syndrome, and/or accompanying accelerated atherosclerosis. Digital ischemia can also occur in the context of disseminated bacterial infections and sepsis. We present here the case of a patient who had digital ischemia and positive antinuclear antibodies but without well-defined clinical features of a connective tissue disease. A diagnosis of undifferentiated connective tissue disease was made.