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The main goal of this study is to investigate the strength and compaction characteristics of soil stabilized by fly ash with multiwalled carbon nanotube (MWCNT) as an additive. The materials used in the study were characterized using microscopic techniques like scanning electron microscopy-energy dispersive spectroscopy (SEM–EDS), and X-ray diffraction (XRD). The soil in the current study was replaced up to 50% by fly ash in the presence of MWCNT and sodium hexametaphosphate (SHMP) in different concentrations. The findings demonstrate that the Atterberg limits and specific gravity decrease with the increase in fly ash, MWCNT, and, SHMP. The maximum (46%) and minimum (24.2%) values of the liquid limit were recorded at 0% and 50% fly ash content, respectively. The maximum (34%) and minimum (20.2%) values of the plastic limit were observed at 0% and 50% fly ash content respectively. The specific gravity of natural soil decreases from the maximum value of 2.68 to the minimum value of 2.53 at 0% and 50% fly ash content, respectively. The optimum moisture content also decreases with the increase in fly ash, MWCNT, SHMP, and vice versa for maximum dry density. 0.01% w/w MWCNT + 80% Soil + 20% Fly Ash + 2% SHMP is the optimal mix. It gives maximum unconfined compressive strength (UCS) value in all the durations of curing, i.e. 0.50, 0.725, and 0.984 MPa at 1, 7, and 28 days of curing, respectively. The UCS value of this combination is 147% more than the UCS value of normal soil cured for 28 days. An economic analysis is also conducted to understand the feasibility of the application of MWCNTs in soil-fly ash mix. [ABSTRACT FROM AUTHOR]

Growing concern over the combustion cost and environment has made road engineers and scientists to explore the possible use of locally available materials for the construction of roads. The present study evaluated the strength and durability characteristics of five sites having locally available silty soils using lime and cement–sand stabilization technique. The test results showed that the cement–sand stabilization technique using 6% cement and 5% local sand resulted in higher strength and durability as compared to lime stabilization. There is also a significant increase in the value of the soaked California bearing ratio (CBR). As unconfined compressive strength (UCS) attained the threshold strength as prescribed by IRC SP 72 2015 for the granular sub-base (GSB) layer, by the use of sand cement stabilization, this technique of stabilization for local silty soils could be used for GSB for low volume road (LVR) construction. As observed from microstructural results which were performed by analysing SEM images, sand cement stabilisation leads to CSH gel and agglomerate formation thereby increasing strength and durability properties. The cost analysis for the replaced stabilized GSB layer showed that using sand–cement stabilization, the estimated cost can be reduced by 56% of the total cost as compared to the conventional method. [ABSTRACT FROM AUTHOR]

Warm mix asphalt mixtures became attractive paving mixes by reducing the production temperature to around 25–40 °C as compared to that of conventional hot mix asphalt (HMA). This study aims to evaluate the warm mix asphalt (WMA) using wax-based additives by incorporating two types of industrial wastes. The potential application of low calcium fly ash (FA), i.e. class F type and marble dust (MD), has been evaluated by varying different percentage. The cylindrical samples were prepared and assessed for moisture susceptibility by being subjected to Marshall stability, retained Marshall stability (RMS), indirect tensile strength (ITS) and tensile strength ratio (TSR) tests. Furthermore, the samples were also evaluated for finding the refusal density, Cantabro loss and the rutting performance. A scanning electron microscope (SEM) was also used to evaluate the size and microstructure of the filler particles. The results revealed that the inclusion of fillers into mixes had significant improvement in the mechanical properties and lowered the rutting value with FA and MD addition. The warm mix additive and fillers used were also useful in reducing the binder content of the mixes. The mixing temperature was found to be in the range of 120–130 °C using the warm mix additive. The optimum usage of FA and MD can be up to 5% based on the evaluation. The statistical results reported that there was a significant difference between FA-based and MD-based WMA. [ABSTRACT FROM AUTHOR]

Low-volume roads are anticipated to have less traffic and provide access to socio-economic activities in rural areas. The present study deals with the stabilisation of soil with locally available waste materials, i.e. low calcium fly ash (FA) and brick dust (BD). These two wastes are available abundantly and lead to an increase in pollution levels. Initially, lime was added to make the silty clayey soils plastic-free. The initial consumption of lime was found to be 5%. Then, the soil was stabilised with cement fly ash and cement brick dust techniques for strength, durability and shrinkage evaluation. The cement was varied from 2 to 8% with FA and BD by fixing the ratio to 1:3 as per AASHTO guidelines. The unconfined compressive strength (UCS), indirect tensile strength test and California bearing ratio were conducted for strength evaluation. The wetting and drying cycles were evaluated for durability analysis. The linear shrinkage cracking was evaluated after the curing period of 28 days. It was observed that there was a magnificent increase in strength and durability values. The maximum UCS attained value was so high that it could act as a replacement for the granular sub-base layer in the pavement structure. The linear shrinkage evaluated at fixed relative humidity was significantly reduced. The statistical analysis reported that there was a significant difference between the two admixtures. The utilisation of these wastes not only enhances strength, but also deficits the cost of construction along with reducing the pollutants in the environment. [ABSTRACT FROM AUTHOR]

This investigation is primarily focused on addressing the prevailing uncertainty surrounding the compressive strength of three distinct types of bricks: nanomodified; simple; and commercial. Nanomodified bricks are specifically fabricated using a minute concentration of 0.01% w/w multiwalled carbon nanotubes combined with 1% sodium hexametaphosphate. However, the utilization of both materials in a single brick is currently limited. In view of this constraint, a diligent effort was made in this study to comprehend the effects of multiwalled carbon nanotubes and sodium hexametaphosphate as additive materials for brick construction. It is important to note that the compressive strength of the bricks remains the pivotal and critical characteristic under investigation, and an exhaustive analysis was undertaken employing a probabilistic approach. The findings of the study suggest that the variability observed in the compressive strength parameters of nanomodified, simple, and commercial bricks can be explained by a normal distribution at a significance level of 5%. The calculated values for the characteristic compressive strength were determined to be 24.47, 16.47, and 14.24 N/mm2 , respectively, for the three types of bricks. Further, the regression analysis conducted to assess the relationship between brick compressive strength and the independent variables yielded a cubic fit with R2 (coefficient of determination) values of 0.984, 0.995, and 0.995 for nanomodified, simple, and commercial bricks, respectively. Consequently, the application of multiwalled carbon nanotubes in conjunction with sodium hexametaphosphate in fired clay bricks can be recommended to achieve enhanced compressive strength. [ABSTRACT FROM AUTHOR]

Warm-mix asphalt (WMA) is produced at lower temperatures—about 30°C–40°C lower—than hot-mix asphalt (HMA). Huge amounts of brick dust (BD) and fly ash (FA) are generated every year throughout the world, causing an environmental hazard, and their disposal is a serious problem. In addition, the high mixing temperature of HMA production increases environmental load. This study evaluated warm mixes made using organic wax and chemical-based technologies. Two types of filler material, i.e., FA and BD, were used as binary blended fillers (BBF). Cylindrical Marshall specimens were prepared and subjected to moisture susceptibility tests for both aged and unaged conditions. The durability of these samples was tested by evaluating the tensile strength ratio using the modified Lottman test method. The cohesion resistance of the mixtures was evaluated by Cantabro loss. Furthermore, a wheel tracker test (WTT) setup was used for rutting evaluation. Results revealed that the use of BBF in mixes led to a marked increase in mechanical properties. Microstructural behavior was studied using scanning electron microscopy (SEM) images for particle-size distribution. The statistical test indicated a significant difference in stability values and rut depths. [ABSTRACT FROM AUTHOR]

Durability of bituminous mixes is affected by presence or intrusion of moisture into it. The intrusion and amount of trapped moisture largely depend on the air voids present in the mixes. This study explores the combined influence of air voids and hydrated lime (HL, as anti-stripping agent) on moisture-induced damage of bituminous mixes prepared from two different aggregate sources. The aggregates used in the study are siliceous sandstone and basalt. Tensile Strength Ratio (TSR) test was used to determine the moisture susceptibility of bituminous mixes. A higher value of TSR depicts that the mixes are more moisture resistant. TSR was reaffirmed to be lowest at an air void range of about 5% to 13% which is termed as pessimum air void range. At this air void range, moisture gets trapped within the mix, resulting in moisture-induced damage. TSR results showed that bituminous mixes prepared with siliceous sandstone is more susceptible to moisture-induced damage as compared to mixes prepared with basalt. Boil water test reconfirmed the results. Use of HL in bituminous mixes improved its moisture-induced damage resistance only marginally. Thus, moisture-induced damage control at pessimum air void range using anti-stripping agent is not always sufficient. Observations show that air void plays a critical role in moisture-induced damage and control of air void during construction needs to be ensured. [ABSTRACT FROM AUTHOR]

Background: The immunomodulatory effects of vitamin D are widely recognized and a few studies have been conducted to determine its utility in the treatment of tuberculosis, with mixed results. This study was conducted to see if vitamin D supplementation in patients with active pulmonary tuberculosis (PTB) in the Indian population contributed to sputum smear and culture conversion as well as the prevention of relapse. Methods: This randomized double-blind placebo-controlled trial was conducted in three sites in India. HIV negative participants aged 15–60 years with sputum smear positive PTB were recruited according to the Revised National Tuberculosis Control Program guidelines and were randomly assigned (1:1) to receive standard anti-tubercular treatment (ATT) with either supplemental dose of oral vitamin D3 (60,000 IU/sachet weekly for first two months, fortnightly for next four months followed by monthly for the next 18 months) or placebo with same schedule. The primary outcome was relapse of PTB and secondary outcomes were time to conversion of sputum smear and sputum culture. Results: A total of 846 participants were enrolled between February 1, 2017 to February 27, 2021, and randomly assigned to receive either 60,000 IU vitamin D3 (n = 424) or placebo (n = 422) along with standard ATT. Among the 697 who were cured of PTB, relapse occurred in 14 participants from the vitamin D group and 19 participants from the placebo group (hazard risk ratio 0.68, 95%CI 0.34 to 1.37, log rank p value 0.29). Similarly, no statistically significant difference was seen in time to sputum smear and sputum culture conversion between both groups. Five patients died each in vitamin D and placebo groups, but none of the deaths were attributable to the study intervention. Serum levels of vitamin D were significantly raised in the vitamin D group as compared to the placebo group, with other blood parameters not showing any significant difference between groups. Conclusions: The study reveals that vitamin D supplementation does not seem to have any beneficial effect in the treatment of PTB in terms to the prevention of relapse and time to sputum smear and culture conversion. Trial registration: CTRI/2021/02/030977 (ICMR, Clinical trial registry-India). [ABSTRACT FROM AUTHOR]

Introduction: Universal coverage of vaccines alone cannot be relied upon to protect at-risk populations in lower- and middle-income countries against the impact of the coronavirus disease 2019 (COVID-19) pandemic and newer variants. Live vaccines, including Bacillus Calmette–Guérin (BCG), are being studied for their effectiveness in reducing the incidence and severity of COVID-19 infection. Methods: In this multi-centre quadruple-blind, parallel assignment randomised control trial, 495 high-risk group adults (aged 18–60 years) were randomised into BCG and placebo arms and followed up for 9 months from the date of vaccination. The primary outcome was the difference in the incidence of COVID-19 infection at the end of 9 months. Secondary outcomes included the difference in the incidence of severe COVID-19 infections, hospitalisation rates, intensive care unit stay, oxygen requirement and mortality at the end of 9 months. The primary analysis was done on an intention-to-treat basis, while safety analysis was done per protocol. Results: There was no significant difference in the incidence rates of cartridge-based nucleic acid amplification test (CB-NAAT) positive COVID-19 infection [odds ratio (OR) 1.08, 95% confidence interval (CI) 0.54–2.14] in the two groups, but the BCG arm showed a statistically significant decrease in clinically diagnosed (symptomatic) probable COVID-19 infections (OR 0.38, 95% CI 0.20–0.72). Compared with the BCG arm, significantly more patients developed severe COVID-19 pneumonia (CB-NAAT positive) and required hospitalisation and oxygen in the placebo arm (six versus none; p = 0.03). One patient belonging to the placebo arm required intensive care unit (ICU) stay and died. BCG had a protective efficacy of 62% (95% CI 28–80%) for likely symptomatic COVID-19 infection. Conclusions: BCG is protective in reducing the incidence of acute respiratory illness (probable symptomatic COVID-19 infection) and severity of the disease, including hospitalisation, in patients belonging to the high-risk group of COVID-19 infection, and the antibody response persists for quite a long time. A multi-centre study with a larger sample size will help to confirm the findings in this study. Clinical Trials Registry: Clinical Trials Registry India (CTRI/2020/07/026668). Plain Language Summary: The Bacillus Calmette–Guérin (BCG) vaccine has been studied previously in several settings, including reducing childhood mortalities due to viral infections and induction of trained immunity and reducing upper respiratory tract infections and pneumonia in older adults. This multi-centre trial has tried to evaluate the efficacy of BCG revaccination in reducing the incidence and severity of COVID-19 infections in adults between 18 and 60 years of age belonging to the high-risk group owing to the presence of comorbidities including diabetes, chronic kidney disease, chronic liver disease and chronic lung diseases. A single dose of BCG vaccine produced significantly high titres of BCG antibodies lasting for six months. While there was no significant reduction in the incidence of COVID-19 infection, there was an 8.4% reduction in the incidence of symptomatic COVID-19 disease at the end of 9 months of follow-up. In addition, there were significantly fewer severe COVID-19 infections requiring hospital stay and oxygen support. However, the overall numbers of severe COVID-19 infections were low. Thus, the study shows that BCG can protect against symptomatic and severe COVID-19 disease. However, it might not reduce the incidence of new infections. The study results are significant for low- and middle-income countries without adequate coverage of primary doses of COVID-19 vaccination, let alone the booster doses. Future studies should evaluate the BCG vaccine's efficacy as a booster compared with routine COVID-19 vaccine boosters. [ABSTRACT FROM AUTHOR]

In this study, the effect of multiwall carbon nanotubes (MWCNTs) on various properties of a fired clay brick was investigated and subsequently compared with other kinds of bricks. MWCNT doped bricks and traditional bricks were prepared in laboratory conditions and commercially available bricks were obtained from a nearby manufacturer. Each group of bricks were subjected to various tests such as visual examination, dimension tolerance test, efflorescence test, water absorption test, impact resistance test, soundness test, hardness test, structure test, compressive strength test, and scanning electron microscopy (SEM) imaging. An extensive characterization of soil, water, and MWCNT was carried out. X-ray diffraction (XRD), X-ray fluorescence (XRF), and scanning electron microscopy–energy dispersive spectroscopy (SEM-EDS) were done to characterize soil in addition to basic consistency limit tests. MWCNT was characterized using XRD, SEM-EDS, and Fourier transform infrared spectroscopy (FTIR). Soil passing through a 425-μm sieve was used to manufacture MWCNT doped brick (0.01% of water by weight) and traditional bricks. The compressive strength of MWCNT doped bricks was 53.9% and 45.52% more as compared to commercially available and traditional bricks. An adequate reduction in water absorption was recorded when compared with traditional and commercially available bricks. Economic analysis was also carried out, which marked an increase of $0.0134 per brick in the manufacturing of MWCNT doped bricks. [ABSTRACT FROM AUTHOR]

Background & objectives: Several studies have been conducted globally to assess the impact of usage of mobile phones on quality and duration of sleep as also on day time sleepiness. The objective of the present study was to assess the effect of mobile phone usage on the quality and composition of sleep in a sample from Indian population. Methods: The study was conducted at two tertiary care hospitals in north India from July 2014 to September 2019. A total of 566 participants were recruited in this study from both the centres. Sleep quality was assessed with the help of the Pittsburgh Sleep Quality Index (PSQI) questionnaire. Subsequently, actigraphy was done in 96 participants and polysomnography in 95 participants. Results: Of the 566 participants, 128 (22.61%) had PSQI ≥5, reflecting poor sleep quality. A higher use of mobile phone was significantly associated with a poor sleep quality as a component of PSQI questionnaire (P=0.01) and higher overall PSQI score (P=0.01). The latency from sleep onset to N2 and N3 sleep stages was significantly shorter in participants having a higher mobile phone usage as compared to those with a lower usage [Median (range): 13.5 min (1.5-109) vs. 6.5 min (0-89); P=0.02] and [Median (range): 49 min (8.5-220.5) vs. 28.75 min (0-141); P=0.03], respectively. Interpretation & conclusions: This study focused on the maladaptive changes brought on by mobile phone usage on sleep. More studies with larger sample sizes need to be done that may serve to confirm the hypothesis generating findings of our study. [ABSTRACT FROM AUTHOR]

Background & objectives: Despite advances in diagnostics and therapeutics, tuberculosis (TB) is widely prevalent and contributes to a significant burden of illness in both developing and developed nations. The present study was aimed to assess the role of coronin in TB patients and healthy controls. Coronin is a leucocyte-specific protein that is actively recruited in mycobacterial phagolysosomes, where it inhibits lysosomal delivery of Mycobacterium by activating a calcium-dependent phosphatase-calcineurin. Methods: In the study, 100 newly diagnosed cases of TB (pulmonary and extra-pulmonary) and healthy controls were prospectively enrolled over one year and the levels of coronin-1a in these patients and controls were measured by quantitative PCR (qPCR). Results: A total of 100 TB patients and 100 healthy individuals as controls were assessed. There were 59 patients with extra-pulmonary TB (EPTB) and 41 of pulmonary TB (PTB). In 47 per cent of patients, corroborative histopathological evidence of TB was also available. Significantly higher values of coronin-1a were observed in TB patients (19.94±2.61) than in healthy controls (16.09±1.91) (P<0.001). Interpretation & conclusions: Coronin 1a appears to play an important role in the TB disease pathophysiology and agents developed against coronin may have a role in the treatment of TB. Further studies are required to assess if coronin-1a levels are elevated in non-tubercular infective a etiologies and whether these can be a potential drug target in patients with TB. [ABSTRACT FROM AUTHOR]

Correction to: Efficacy of Bacillus Calmette-Guérin (BCG) Vaccination in Reducing the Incidence and Severity of COVID-19 in High-Risk Population (BRIC): a Phase III, Multi-centre, Quadruple-Blind Randomised Control Trial The original article can be found online at https://doi.org/10.1007/s40121-022-00703-y. The supplementary material file has been corrected and the original article has been updated. [Extracted from the article]

Background: According to World Health Organization (WHO) guidelines, which have also been adopted by the National AIDS Control Organization (NACO), India, Efavirenz-based Anti-Retroviral Therapy (ART) is better in Human-Immunodeficiency-Virus (HIV)-infected patients who are also being treated with Rifampicin-based Anti-Tuberculous Therapy (ATT). However, Efavirenz is much more expensive. We hypothesize that Nevirapine is a cheaper alternative that possesses equal efficacy as Efavirenz in HIV-Tuberculosis (TB) co-infected patients.Methods: A parallel open-label randomized clinical trial was conducted at All India Institute of Medical Sciences (AIIMS), New Delhi and National AIDS Research Institute (NARI), Pune. Those who were ART-naïve and co-infected with TB were randomized to receive either Nevirapine (Group 1)- or Efavirenz (Group 2)-based ART along with Rifampicin-based ATT. ATT was begun first in ART-naïve patients according to the NACO guidelines, with a median of 27 days between ATT and ART in both groups. The primary endpoint was a composite unfavourable outcome (death and/or ART failure) at 96 weeks, and the secondary outcome was successful TB treatment at 48 weeks.Results: A total of 284 patients (mean age 36.7 ± 8.1 years) were randomized in a 1:1 ratio to receive either Nevirapine (n = 144)- or Efavirenz (n = 140)-based ART after a median ATT-ART gap of 27 days. The median CD4 count was 105 cells/μl, with a median viral load of 820,200 copies/μl and no significant difference between the groups. Composite unfavourable outcomes were reported in 49 patients in the Nevirapine group and 51 patients in the Efavirenz group (35.3% vs. 36.9%; hazard ratio, 0.95, 95% confidence interval (CI), 0.63,1.43, adjusted). There was no difference in successful TB treatment outcome between the groups (71.5% vs. 65.6%, 95% CI -3.8,17.9, adjusted). The results were similar, showing no difference between the groups in the two centres of the study after adjusting for disease stage.Conclusions: Composite unfavourable outcome in HIV-TB co-infected patients who were ART-naïve showed no statistically significant difference in the Nevirapine or Efavirenz groups.. Therefore, Nevirapine-based ART is a reasonable alternative to Efavirenz in resource-limited settings. However, multi-centric studies with larger sample sizes are required to confirm these findings.Trial Registration: NCT01805258 (Retrospectively registered on March 6, 2013) Date of registration: March 2013. [ABSTRACT FROM AUTHOR]

Warm mix asphalt (WMA) has the advantage of lower production temperature as compared to conventional hot mix asphalt (HMA). It is prepared by using various types of technologies which change the properties of bitumen binder attributes to ease in workability of the mixes. In the present study, bitumen emulsion was used for preparing WMA mixes by pre-coating the aggregates. Moreover, the conventional filler used in such mixes was replaced with industrial wastes to further reap environmental benefits. Marble dust (MD) and ground granulated blast-furnace slag (GGBS) are generated abundantly and disposal is a big issue. These were used in varying contents (i.e. from 2% to 8% by the weight of mix) and WMA properties were evaluated for strength and durability. Marshall properties and indirect tensile strength test (ITS) were carried out for strength evaluation. The tensile strength ratio (TSR) was conducted as per AASHTO T 283 for durability analysis. The wheel tracker test was performed for rutting analysis. Cantabro loss was determined to assess the cohesion resistance of the asphalt mixtures. Scanning electron microscopy (SEM) images were used to assess the microscopic characteristics of WMA and its constituents. The results revealed that the inclusion of both MD and GGBS as fillers into WMA had significantly improved the stability, tensile strength, TSR, rutting and Cantabro loss results as compared to the control mix. However, the addition of GGBS filler in emulsified warm mixes showed better resistance to moisture too. Lower rut depth was observed using GGBS as compared to marble dust filler. The statistical analysis reported that there was a significant difference between stability and TSR values whereas for adhesion loss it showed insignificant difference between the GGBS and MD based mixes. [ABSTRACT FROM AUTHOR]

Background: Procalcitonin is useful for the diagnosis of sepsis but its prognostic value regarding mortality is unclear. This prospective observational study was designed to study the prognostic value of procalcitonin in prediction of 28 day mortality in patients of sepsis. Fifty-four consecutive patients of sepsis, severe sepsis and septic shock defined using the 2001 Consensus Conference SCCM/ESICM/ACCP/ATS/SIS criteria from medical Intensive Care Unit (ICU) of a tertiary care center in New Delhi, India were enrolled from July 2011 to June 2013. Procalcitonin (PCT), C-reactive protein (CRP) measurements were recorded on day 1, day 7 and day 28 of follow up. Results: Procalcitonin value was a better predictor of all-cause short-term mortality than C-reactive protein. Those patients with Procalcitonin levels <7 ng/ml showed higher cumulative survival than those with level [greater than or equal to]7 ng/ml (69.1% vs. 39.5%, p = 0.02). No such effect was observed in relation to C-reactive protein. Procalcitonin levels [greater than or equal to]7 ng/ml predicted mortality with a hazard ratio of 2.6(1.1-6.3). Conclusions: A Procalcitonin value [greater than or equal to]7 ng/ml obtained at the time of admission to the ICU is a predictor of short-term mortality and thus may allow the identification of those septic patients at increased mortality risk, and help improve their treatment. [ABSTRACT FROM AUTHOR]

Background The brain is a target for diabetic end-organ damage, though the pathophysiology of diabetic encephalopathy is still not well understood. The aim of the present study was to investigate the effect of diabetes on the metabolic profile of brain of patients having diabetes in comparison to healthy controls, using in-vivo magnetic resonance spectroscopy to get an insight into the pathophysiology of cerebral damages caused due to diabetes. Methods Single voxel proton magnetic resonance spectroscopy (1H-MRS) was performed at 1.5 T on right frontal, right parieto-temporal and right parieto-occipital white matter regions of the brain of 10 patients having type-2 diabetes along with 7 healthy controls. Absolute concentration of N-acetylaspartate (NAA), choline (cho), myo-inositol (mI), glutamate (Glu) and glutamine (Gln), creatine (Cr) and glucose were determined using the LC-Model and compared between the two groups. Results The concentration of N-acetylaspartate was significantly lower in the right frontal [4.35 ±0.69 vs. 5.23 ±0.74; p = 0.03] and right parieto-occipital region [5.44 ±0.52 vs.6.08 ±0.25; p = 0.02] of the brain of diabetics as compared to the control group. The concentrations of glutamate and glutamine were found to be significantly higher in the right frontal region of the brain [7.98 ±2.57 vs. 5.32 ±1.43; P = 0.01] in diabetics. Glucose levels were found significantly elevated in all the three regions of the brain in diabetics as compared to the control group. However, no significant changes in levels of choline, myo-inositol and creatine were observed in the three regions of the brain examined among the two groups. Conclusions 1H-MRS analysis indicates that type-2 diabetes mellitus may cause subtle changes in the metabolic profile of the brain. Decreased concentrations of NAA might be indicative of decreased neuronal viability in diabetics while elevated concentrations of Gln and Glu might be related to the fluid imbalance resulting from disruption of glucose homeostasis. [ABSTRACT FROM AUTHOR]

Background Administration of rifampicin along with nevirapine reduces the plasma concentration of nevirapine in human immunodeficiency virus positive individuals with concomitant tuberculosis (HIV-TB patients). Nevirapine is a much cheaper drug than its alternative efavirenz, and might be beneficial in resource constrained settings. Methods A randomised open label trial was conducted at All India Institute of Medical Sciences, New Delhi, India. During the regimen of an antiretroviral therapy (ART), naive HIV-TB patients were randomly assigned to receive either nevirapine or efavirenz based ART with concomitant rifampicin based anti-tubercular therapy (ATT). Participants were followed for 24 months after starting ART. The end points were virological, immunological and clinical responses, and progression of HIV disease marked by failure of ART. Results Of the 135 HIV-TB patients, who were receiving rifampicin based ATT, 68 were selected randomly to receive efavirenz based ART and 67 to receive nevirapine based ART. The virological failure rates in the overall population, and the nevirapine and efavirenz groups were 14 ∙ 1% (19/135); 14.9% (10/67) and 13.2% (9/68), respectively (p = 0.94). No significant difference was found between the groups in the rate of clinical, immunological or virological failures. The overall mortality was 17% with no significant difference between the two groups. Except for the lead in period on day 14, the mean nevirapine concentration remained above 3 mg/L. No association was found between plasma levels of nevirapine and incidence of unfavourable outcomes in this group. Conclusions Outcome of ART in HIV-TB patients on rifampicin based ATT showed no significant difference, irrespective of whether efavirenz or nevirapine was used. Therefore, nevirapine based ART could be an alternative in the resource limited settings in patients with HIV and tuberculosis co-infection. Trial Registration Trial Registration: Clinical Trials NCT01805258. [ABSTRACT FROM AUTHOR]

Introduction: Symptomatic cardiac involvement is seen in less than 5% of all cases of sarcoidosis. Although clinically apparent cardiac sarcoidosis is an uncommon entity, ventricular tachyarrhythmias as the first presenting symptom are very rare.Case Presentation: We discuss the case of a 41-year-old Asian woman who presented to our hospital with intermittent palpitation and on evaluation was diagnosed to have systemic sarcoidosis with cardiac involvement. She was started on multiple antiarrhythmic drugs and corticosteroids without any satisfactory response.Conclusions: Our case report indicates that sarcoidosis can manifest as ventricular tachycardia without any detectable systemic findings. This makes sarcoidosis an important diagnostic consideration in patients with ventricular tachycardia of unknown origin given the high mortality associated with ventricular tachyarrhythmias. [ABSTRACT FROM AUTHOR]

Background: For antiretroviral therapy (ART) naive human immunodeficiency virus (HIV) infected adults suffering from tuberculosis (TB), there is uncertainty about the optimal time to initiate highly active antiretroviral therapy (HAART) after starting antituberculosis treatment (ATT), in order to minimize mortality, HIV disease progression, and adverse events. Methods: In a randomized, open label trial at All India Institute of Medical Sciences, New Delhi, India, eligible HIV positive individuals with a diagnosis of TB were randomly assigned to receive HAART after 2-4 or 8-12 weeks of starting ATT, and were followed for 12 months after HAART initiation. Participants received directly observed therapy short course (DOTS) for TB, and an antiretroviral regimen comprising stavudine or zidovudine, lamivudine, and efavirenz. Primary end points were death from any cause, and progression of HIV disease marked by failure of ART. Findings: A total of 150 patients with HIV and TB were initiated on HAART: 88 received it after 2-4 weeks (early ART) and 62 after 8-12 weeks (delayed ART) of starting ATT. There was no significant difference in mortality between the groups after the introduction of HAART. However, incidence of ART failure was 31% in delayed versus 16% in early ART arm (p = 0.045). Kaplan Meier disease progression free survival at 12 months was 79% for early versus 64% for the delayed ART arm (p = 0.05). Rates of adverse events were similar. Interpretation: Early initiation of HAART for patients with HIV and TB significantly decreases incidence of HIV disease progression and has good tolerability. [ABSTRACT FROM AUTHOR]

Researchers explored the barriers to AIDS care for rural women living with AIDS, and they investigated alternative delivery models to increase the women's adherence to antiretroviral therapy (ART). Community-based participatory research focus groups were conducted by the researchers with a convenience sample of 39 women living with AIDS from a primary health center (PHC) near Chennai, India, and with nurses, physicians, and Accredited Social Health Activists (Ashas), who are lay health care workers. The most prevalent barriers expressed by the women were sickness-related, psychological, financial issues with childcare, and distance, or transportation to the site. Women living with AIDS reviewed Ashas favorably. [ABSTRACT FROM AUTHOR]

Abstract: Objective: To study hepatic gluconeogenesis pathway in non-diabetic Asian Indian males having non-alcoholic fatty liver disease (NAFLD) using in vivo (31P) phosphorous magnetic resonance spectroscopy (MRS) and correlate these data with anthropometry and insulin resistance. Research design and methods: Forty non-diabetic patients with NAFLD and 20 healthy controls were divided into (i) obese with NAFLD (group I, n =20), (ii) non-obese with NAFLD (group II, n =20) and (iii) non-obese without NAFLD (group III, n =20). Anthropometric and biochemical profiles, short insulin tolerance test (SITT), liver ultrasound, and 31P MRS (to determine hepatic gluconeogenesis metabolite; phosphomonoesters (PMEs), inorganic phosphate (Pi) and their ratios with respect to ATP) were done. Results: Insulin resistance (Kitt value) was highest in group I (p <0.05; compared to other two groups), but was also higher in group II as compared to group III (p =ns). The values of PME/Pi, PME/γATP, PME/βATP, PME/tATP ratios were higher (p <0.05) in group I compared to other two groups. Interestingly, non-obese subjects with NAFLD also showed more derangements of hepatic gluconeogenesis metabolites than non-obese subjects without NAFLD. Positive correlation was observed between PME and other ratios in relation to body mass index, waist circumference, body fat percentage and fasting serum insulin levels in all the three groups. Conclusions: Derangements in hepatic gluconeogenesis as assessed non-invasively using 31P MRS, was observed in obese and non-obese, non-diabetic Asian Indians with NAFLD. Further research is warranted whether this investigation in NAFLD subjects could be developed as a non-invasive tool to assess those predisposed to develop hyperglycemia. [Copyright &y& Elsevier]

Abstract: We report the determination of intramyocellular lipids (IMCLs) of the soleus muscle of patients with type 2 diabetes mellitus (T2DM) using proton magnetic resonance spectroscopy. In addition, the various anthropometric and biochemical profiles of these patients were determined, including estimation of C-reactive protein (CRP), an inflammatory marker of coronary heart disease, and insulin resistance [Homeostasis Model Assessment (HOMA-IR)]. The estimated CRP level and the IMCL content in these patients were correlated with body mass index, percentage of body fat, other measures of abdominal obesity, serum lipoproteins, fasting and post-oral glucose load serum insulin levels and other surrogate markers of insulin resistance. The IMCL content (P=.04), CRP (P=.008) and insulin resistance (P=.0007) were significantly higher in T2DM patients compared to healthy controls. However, IMCL content did not correlate with values of fasting insulin, HOMA-IR or CRP in either group. These findings have strong implications of increased cardiovascular risk in Asian Indians with T2DM. The absence of relationship between CRP and IMCL needs to be explored further in a study using a large sample size. [Copyright &y& Elsevier]

The relationship between C-reactive protein (CRP), a marker of subclinical inflammation, and intramyocellular lipid (IMCL) content, a novel correlate of insulin resistance, has not previously been investigated. We estimated IMCL content in soleus muscle in 30 healthy Asian Indian males using proton magnetic resonance spectroscopy (1H MRS), and correlated it with body mass index (BMI), measures of abdominal obesity, percentage of body fat (%BF), serum lipoproteins, fasting and post-oral glucose load serum insulin levels and other surrogate markers of insulin resistance. Soleus muscle IMCL content was significantly correlated with age (ρ = 0·64, P < 0·001), BMI (ρ = 0·41, P < 0·05), %BF (ρ = 0·53, P ≤ 0·01), waist circumference (ρ = 0·45, P < 0·05) and waist-to-hip circumference ratio (ρ = 0·58, P < 0·01) but did not correlate significantly with insulin resistance measured by the homeostasis model assessment (HOMA-IR) or CRP levels. CRP levels did not correlate with the HOMA-IR value. Soleus muscle IMCL content correlated significantly with measures of generalized and abdominal obesity but not with insulin sensitivity or CRP levels in healthy Asian Indian males. Studies are needed in other ethnic groups to corroborate these data. [ABSTRACT FROM AUTHOR]

To evaluate brain metabolism and cerebral blood flow in young patients with hyperlipidaemia. Proton magnetic resonance spectroscopy (1H MRS) and single photon emission computed tomography (SPECT) of the brain was carried out in 19 asymptomatic young patients with hyperlipidaemia (mean age 32·6 ± 6·0 years, range 22–45 years) and 21 age-matched healthy controls divided into the following three groups; (i) hyperlipidaemics on pharmacological treatment (group 1, n = 13), (ii) hyperlipidaemics not on pharmacological treatment (group 2, n = 6) and (iii) control group of healthy subjects (group 3, n = 21). No statistical difference was observed in the brain metabolite ratios between controls and hyperlipidaemic patients (both treatment naive and treated) in the 1H NMR study. Two hyperlipidaemic patients showed a lactate peak and one had a lipid peak. The SPECT study was abnormal in seven hyperlipidaemic patients. In the pooled data, 50% subjects with high serum triglyceride (TG) levels as opposed to 14% subjects with normal serum TG levels showed cerebral hypoperfusion. The choline/creatine (Cho/Cr) ratio of the occipital region of the brain showed correlation with the excess percentage of body fat (%BF) and low levels of high density lipoprotein cholesterol (HDL-C) compared to those with normal %BF and normal HDL-C levels, respectively, in pooled data of all subjects. The N-acetyl aspartate (NAA)/Cho ratio also showed correlation with hypercholesterolaemia. Serum TG levels were positively correlated with the NAA/Cr ratio ( r = 0·62, P < 0·05) and the Cho/Cr ratio ( r = 0·63, P < 0·05) in the parieto-temporal area in group 1 patients. The study revealed no difference in the brain metabolite ratios between controls and hyperlipidaemic patients, while some hyperlipidaemic patients showed abnormalities of cerebral blood flow. Brain metabolite ratios were also influenced by certain parameters of body composition and lipids. As abnormal body composition, hypertriglyceridaemia and low levels of HDL-C are prevalent in Asian Indians, such data are important and indicate a need for further study. [ABSTRACT FROM AUTHOR]

A tubercular retropharyngeal abscess is rare in immunocompetent adults. In the case of a tubercular retropharyngeal abscess, it is usually due to cervical spine tuberculosis and is seen mostly in children. A 19-year-old female patient presented to our Medicine Outpatient Department (OPD) at All India Institute of Medical Sciences (AIIMS) with odynophagia and neck pain for two months, without any other constitutional symptoms. On evaluation, she was diagnosed with tubercular retropharyngeal abscess along with pulmonary tuberculosis, without involvement of the cervical spine. This patient was successfully treated by antituberculosis drug therapy alone, without any need for surgical drainage. [ABSTRACT FROM AUTHOR]

Background: Chronic pulmonary aspergillosis (CPA) is known to complicate patients with post‐tubercular lung disease. However, some evidence suggests that CPA might co‐exist in patients with newly‐diagnosed pulmonary tuberculosis (P.TB) at diagnosis and also develop during therapy. The objective of this study was to confirm the presence of CPA in newly diagnosed P.TB at baseline and at the end‐of‐TB‐therapy. Materials and Methods: This prospective longitudinal study included newly diagnosed P.TB patients, followed up at third month and end‐of‐TB‐therapy with symptom assessment, anti‐Aspergillus IgG antibody and imaging of chest for diagnosing CPA. Results: We recruited 255 patients at baseline out of which 158 (62%) completed their follow‐up. Anti‐Aspergillus IgG was positive in 11.1% at baseline and 27.8% at end‐of‐TB‐therapy. Overall, proven CPA was diagnosed in 7% at baseline and 14.5% at the end‐of‐TB‐therapy. Around 6% patients had evidence of aspergilloma in CT chest at the end‐of‐TB‐therapy. Conclusions: CPA can be present in newly diagnosed P.TB patients at diagnosis and also develop during anti‐tubercular treatment. Patients with persistent symptoms or developing new symptoms during treatment for P.TB should be evaluated for CPA. Whether patients with concomitant P.TB and CPA, while receiving antitubercular therapy, need additional antifungal therapy, needs to be evaluated in future studies. [ABSTRACT FROM AUTHOR]

Background: Bronchoalveolar lavage (BAL) galactomannan (GM) is commonly used to diagnose Aspergillus‐related lung diseases. However, unlike serum GM, which is measured in undiluted blood, BAL‐GM is estimated using variable aliquots and cumulative volume of instillates during bronchoscopy. Objective: Since different studies have reported varying diagnostic accuracy and cut‐offs for BAL‐GM in CPA, we hypothesized that the total volume of instillate and ‘order/label’ of aliquots significantly affects the BAL‐GM values, which was evaluated as part of this study. Patients & Methods: We obtained 250 BAL samples from 50 patients (five from each) with suspected chronic pulmonary aspergillosis. BAL fluid was collected after instilling sequential volumes of 40 mL of normal saline each for the first four labels and a fifth label was prepared by mixing 1 mL from each of the previous labels. The GM level of each label was measured by PLATELIA™ ASPERGILLUS Ag enzyme immunoassay. This study measured the discordance, level of agreement, diagnostic characteristics (sensitivity, specificity and AUROC) and best cut‐offs for BAL‐GM in the different aliquots of lavage fluid. Results: The study population, classified into CPA (28%) and non‐CPA (72%) groups, based on ERS/ESCMID criteria (excluding BAL‐GM) were not different with respect to clinico‐radiological characteristics. The discordance of BAL‐GM positivity (using a cut‐off of >1) between the serial labels for the same patient ranged between 10% and 22%, while the discordance between classification using BAL‐GM positivity (using a cut‐off of ≥1) and clinic‐radio‐microbiological classification ranged between 18% and 30%. The level of agreement for serial labels was at best fair (<0.6 for all except one ‘label’). The AUROC for the serial samples ranged between 0.595 and 0.702, with the ‘40 mL and the ‘mix’ samples performing the best. The best BAL‐GM cut‐off also showed significant variation between serial labels of varying dilutions (Range:1.01 ‐ 4.26). Interpretation: This study highlights the variation in BAL‐GM measured and the ‘positivity’ between different ‘labels’ of aliquots of BAL, with the first aliquot and the mixed sample showing the best performances for diagnosis of CPA. Future studies should attempt to ‘standardise’ the instilled volume for BAL‐GM estimation to standardise the diagnostic yield. [ABSTRACT FROM AUTHOR]

Supplemental Digital Content is Available in the Text. Background: Women living with HIV (WLH) in rural communities face challenges to obtaining treatment and accurate disease-related information. Nutritional deficits exacerbate disease progression. Setting: WLH were recruited from primary health centers in rural India. Method: A quasi-experimental trial of a comprehensive Accredited Social Health Activist (Asha)-supported intervention compared 4 distinct Asha-based programs [(1) standard education (SE) alone; (2) nutrition education (+NE); (3) nutrition supplements (+NS); or (4) nutrition education and nutrition supplements (+NENS)] on key disease and nutrition-related outcomes [CD4 count, body mass index (BMI), serum albumin, and hemoglobin]. Assessments occurred at baseline, and months 6 (immediately after intervention), 12, and 18. Multilevel modeling examined effects of program (group) over time. Findings: Among 600 WLH enrolled (n = 150 per arm), mean age, CD4 count, and BMI (kg/m2) were 34.31, 447.42, and 20.09, respectively, at baseline. At 18-month follow-up, program 4 (+NENS) experienced greatest improvements in CD4 counts compared with program 1 (+SE) [adjusted difference = 223.81, 95% confidence interval (CI): 170.29 to 277.32]. For BMI, programs 3 (+NS; adjusted difference = 2.33, 95% CI: 1.39 to 3.26) and 4 (+NENS; adjusted difference = 2.14, 95% CI: 1.17 to 3.12) exhibited greater gains compared with program 1 (+SE). Programs 3 and 4 were not significantly different from each other (adjusted difference = −0.18, 95% CI: −1.12 to 0.76). Hemoglobin and serum albumin also improved over time; program 4 (+NENS) exhibited the greatest gains. Conclusions: A low-cost Asha-supported behavioral and nutritional intervention improved outcomes for WLH. Gains were sustained at 18-month follow-up. Similar approaches may help improve HIV and other infectious disease-related outcomes in vulnerable populations. [ABSTRACT FROM AUTHOR]

Context • Gas discharge visualization (GDV) works on the principle of the Kirlian effect. It’s a noninvasive, quick, and safe biometric tool to investigate the psychophysiological state of an individual, with the potential to identify deviations from the healthy functioning of humans at early stages. Objective • The study intended to systematically document the scientific evidence pertaining to the use of GDV devices in human health and disease conditions. Design • The research team performed a systematic search for studies on GDV on research databases such as Google Scholar, PubMed, and PsychINFO, using the following inclusion criteria: (1) experimental studies dealing with a GDV device, (2) studies dealing with human participants related to health and disease, and (3) studies published in the English language. The study excluded: (1) review articles, (2) case studies, (3) letter to editors, (4) studies with unclear methodology, and (5) studies published before the year 2000. Setting • The study took place in the Department of Integrative Medicine at the National Institute of Mental Health and Neurosciences (NIMHANS) in Bengaluru, India. Results • After filtering, the research team obtained 108 publications that dealt with the application of a GDV device in human participants. Based on the selection criteria, 42 studies were included in the review. These 42 studies included eight randomized controlled trials (RCTs), five nonrandomized controlled studies, 17 crosssectional studies, 10 single-group pre-post studies, and two correlational studies. Conclusions • More studies with a robust methodology are needed to make definitive conclusions. The literature reveals that the GDV technique has the potential to provide early diagnosis and screening, especially in disorders of the endocrine and immune systems. It might also be used to assess wellness in healthy subjects and monitor the effects of interventions, such as yoga— including pranayama and meditation, acupuncture, qigong, music therapy, and massage on the human energy system. Future studies should focus on the validation of GDV imaging in clinical settings. [ABSTRACT FROM AUTHOR]

Background: Sleep-disordered breathing (SDB) is common in patients with end-stage renal disease (ESRD). SDB is associated with comorbidities such as hypertension, diabetes mellitus, and obesity, interplaying with metabolic derangements in the form of uremia, acidosis, and hypervolemia. Renal transplant has been observed to correct most of these metabolic derangements and to control progression of comorbidities. While SDB is highly prevalent among patients in the pretransplant stage, it remains to be seen whether the beneficial aspects of transplant are extended to improvement in SDB in patients with ESRD.Methods: Eighteen patients undergoing thrice-weekly hemodialysis (HD) for ESRD at the transplant clinic of All India Institute of Medical Sciences (AIIMS), New Delhi, underwent detailed clinical, laboratory, and polysomnographic evaluation. The average number of apneas and hypopneas per hour of sleep, ie, Apnea-Hypopnea Index (AHI), was used to define the severity of sleep apnea. All patients underwent polysomnography (PSG) within 24 h of the last HD and after three months of living-donor transplant.Results: Of 18 patients, there were 14 males and four females. The median age was 28 years (range 19-50 years). They had already spent a median period of six months (range 3-31 months) on HD before inclusion. The prevalence of SDB (AHI ≥ 5/h) was 44.4% (8/18) before transplant, which decreased to 5.6% (1/18) after transplant (p = 0.016). The oxygen desaturation index had a median value of 5.8 events/h (range 0.1-35.4) in the pretransplant stage, which decreased to 0 events/h (range 0-6.6) in the post-transplant stage (p = 0.035).Conclusion: There was a significant improvement in the prevalence and severity of SDB after transplant. Whether improvement in SDB is sustained on a long-term follow-up remains to be seen. [ABSTRACT FROM AUTHOR]

Introduction: Patients on central lines are often having multiple morbidities, and invasive devices provide a niche for biofilm formation, which makes central line-associated bloodstream infections (CLABSIs), a serious concern in health-care settings, as the infections difficult to treat. In this study, we evaluated the common bacteria causing CLABSI, and various patient and pathogen factors affecting the clinical outcome. Methods: In the prospective observational study, patients diagnosed with CLABSI were recruited. Extensive clinical, microbiological, and other laboratory workup was done, and observations were recorded. Congo red agar method, tube test, and microtiter plate assay were used for eliciting the biofilm-forming attributes of the bacterial pathogens. Results: Klebsiella pneumoniae was responsible for 48% of CLABSI, followed by Coagulase-negative Staphylococci (16%) and Staphylococcus aureus and Acinetobacter baumannii (12% each). Fifty-six percent of the isolates produced biofilms. The median (interquartile range) duration of hospital stay till death or discharge was 30 (20, 43) days. The all-cause mortality was 44%. Patients having a deranged liver function on the day of diagnosis (P value for total bilirubin 0.001 and for aspartate transaminase 0.02), and those infected with multidrug-resistant organisms (P value = 0.04) had significantly poor prognosis. The difference in the demographic, clinical, laboratory profile, and outcome of patients infected with biofilm producers and nonproducers was not found to be statistically significant. Conclusion: The study throws light on various host and pathogen factors determining the cause and outcome of CLABSI patients. To the best of our knowledge, this is the first study trying to decipher the role of biofilm formation in the virulence of pathogens and the prognosis of CLABSI. [ABSTRACT FROM AUTHOR]

Background: Administration of rifampicin along with nevirapine reduces the plasma concentration of nevirapine in human immunodeficiency virus positive individuals with concomitant tuberculosis (HIV-TB patients). Nevirapine is a much cheaper drug than its alternative efavirenz, and might be beneficial in resource constrained settings.Methods: A randomised open label trial was conducted at All India Institute of Medical Sciences, New Delhi, India. During the regimen of an antiretroviral therapy (ART), naive HIV-TB patients were randomly assigned to receive either nevirapine or efavirenz based ART with concomitant rifampicin based anti-tubercular therapy (ATT). Participants were followed for 24 months after starting ART. The end points were virological, immunological and clinical responses, and progression of HIV disease marked by failure of ART.Results: Of the 135 HIV-TB patients, who were receiving rifampicin based ATT, 68 were selected randomly to receive efavirenz based ART and 67 to receive nevirapine based ART. The virological failure rates in the overall population, and the nevirapine and efavirenz groups were 14.1% (19/135); 14.9% (10/67) and 13.2% (9/68), respectively (p =0.94). No significant difference was found between the groups in the rate of clinical, immunological or virological failures. The overall mortality was 17% with no significant difference between the two groups. Except for the lead in period on day 14, the mean nevirapine concentration remained above 3 mg/L. No association was found between plasma levels of nevirapine and incidence of unfavourable outcomes in this group.Conclusions: Outcome of ART in HIV-TB patients on rifampicin based ATT showed no significant difference, irrespective of whether efavirenz or nevirapine was used. Therefore, nevirapine based ART could be an alternative in the resource limited settings in patients with HIV and tuberculosis co-infection.Trial Registration: NCT No. 01805258. [ABSTRACT FROM AUTHOR]

In this study, focus groups were conducted with 16 rural women living with AIDS (WLA) from Andhra Pradesh, India, who had previously participated in a clinical trial wherein 68 WLA were randomized into either an Accredited Social Health Activists (ASHA)-Life (AL) intervention or a usual care program. Findings are discussed in terms of (a) mental health issues, (b) perceived stressors, (c) individual resources for coping with mental health issues, and (d) role of ASHA support in coping with mental health issues. These findings highlight the salience of mental health issues in the lives of WLA and the role played by ASHA in addressing some of these issues. The discussion section makes a case for increased emphasis on mental health care in future community-based interventions for this population. [ABSTRACT FROM AUTHOR]

New variants of SARS-CoV-2 continue to evolve. The novel SARS-CoV-2 variant of concern (VOC) B.1.1.529 (Omicron) was particularly menacing due to the presence of numerous consequential mutations. In this study, we reviewed about 12 million SARS-CoV-2 genomic and associated metadata using extensive bioinformatic approaches to understand how evolutionary and mutational changes affect Omicron variant properties. Subsampled global data based analysis of molecular clock in the phylogenetic tree showed 29.56 substitutions per year as the evolutionary rate of five VOCs. We observed extensive mutational changes in the spike structural protein of the Omicron variant. A total of 20% of 7230 amino acid and structural changes exclusive to Omicron's spike protein were detected in the receptor binding domain (RBD), suggesting differential selection pressures exerted during evolution. Analyzing key drug targets revealed mutation-derived differential binding affinities between Delta and Omicron variants. Nine single-RBD substitutions were detected within the binding site of approved therapeutic monoclonal antibodies. T-cell epitope prediction revealed eight immunologically important functional hotspots in three conserved non-structural proteins. A universal vaccine based on these regions may likely protect against all these SARS-CoV-2 variants. We observed key structural changes in the spike protein, which decreased binding affinities, indicating that these changes may help the virus escape host cellular immunity. These findings emphasize the need for continuous genomic surveillance of SARS-CoV-2 to better understand how novel mutations may impact viral spread and disease outcome. [ABSTRACT FROM AUTHOR]

This paper proposes two exposure based recursive histogram equalization methods for image enhancement. The proposed methods are very effective for images acquired in low light condition like underwater sequences or night vision images. The first method is recursive exposure based sub-image histogram equalization (R-ESIHE) that recursively performs ESIHE [20] method till the exposure residue among successive iteration is less than a predefined threshold. The second method is named as recursively separated exposure based sub image histogram equalization (RS-ESIHE) that performs the separation of image histogram recursively; separate each new histogram further based on their respective exposure thresholds and equalize each sub histogram individually. The experimental results show that low exposure image enhancement problem was not addressed by earlier HE based methods, has been efficiently handled by these new methods. The performance evaluation of new methods is done in terms of image information content as well as visual quality inspection. The proposed methods outperforms earlier HE based contrast enhancement algorithms specifically for low light images. [ABSTRACT FROM AUTHOR]

Sepsis is a life-threatening organ dysfunction caused by a dysregulated host response to infection. Septic shock is a subset of sepsis with underlying circulatory cellular and metabolic abnormalities associated with higher mortality rates. However, a detailed understanding of sepsis is still limited. The present study reports the differences in the metabolic profile of serum samples of patients with sepsis compared to healthy controls using Nuclear Magnetic Resonance (NMR) spectroscopy. The study also compares the NMR metabolomics on day zero of admission among sepsis survivors (those who survived till day seven) and sepsis non-survivors (those who succumbed on day zero). Furthermore, the different metabolites in serum were analysed by univariate and multivariate analysis, ROC analysis, principal component analysis (PCA), partial least squares discriminant analysis (PLS-DA) and orthogonal partial least squares discriminant analysis (OPLS-DA) methods. Metabolites with VIP score (>1·0) were considered as potential biomarker/s to discriminate sepsis survivors from non- survivors at day zero. Data showed that phenylalanine was significantly higher in sepsis patients compared to healthy controls, whereas isoleucine, valine and histidine were significantly lower in sepsis patients compared to healthy controls. Also, non-survivors had higher serum levels of creatine, phosphocreatine, choline, betaine, tyrosine, histidine and phenylalanine concentrations than survivors. These findings suggest that the metabolic alterations at day zero may predict the survival of patients with sepsis. The significant differences seen in metabolites concentration of amino acids, phospholipids and creatine may be used as early prognostic markers to discriminate non-survivors from survivors of sepsis patients at day zero. Our findings indicate that the metabolite alterations are associated with the progression of the disease. [ABSTRACT FROM AUTHOR]

Background: The diagnosis of CPA relies on the detection of the IgG Aspergillus antibody, which is not freely available, especially in resource-poor settings. Point-of-care tests like LDBio Aspergillus ICT lateral flow assay, evaluated in only a few studies, have shown promising results for the diagnosis of CPA. However, no study has compared the diagnostic performances of LDBio LFA in setting of tuberculosis endemic countries and have compared it with that of IgG Aspergillus. Objectives: This study aimed to evaluate the diagnostic performances of LDBio LFA in CPA and compare it with existing the diagnostic algorithm utilising ImmunoCAP IgG Aspergillus. Methods: Serial patients presenting with respiratory symptoms (cough, haemoptysis, fever, etc.) for >4 weeks were screened for eligibility. Relevant investigations, including direct microscopy and culture of respiratory secretions, IgG Aspergillus, chest imaging, etc., were done according to existing algorithm. Serums of all patients were tested by LDBio LFA and IgG Aspergillus (ImmunoCAP Asp IgG) and their diagnostic performances were compared. Results: A total of 174 patients were included in the study with ~66.7% patients having past history of tuberculosis. A diagnosis of CPA was made in 74 (42.5%) of patients. The estimated sensitivity and specificity of LDBio LFA was 67.6% (95% CI: 55.7–78%) and 81% (95% CI: 71.9–88.2%), respectively, which increased to 73.3% (95% CI: 60.3–83.9%) and 83.9% (95% CI: 71.7–92.4%), respectively, in patients with a past history of tuberculosis. The sensitivity and specificity of IgG Aspergillus was 82.4% (95% CI: 71.8–90.3%) and 82% (95% CI: 73.1–89%); 86.7% (95% CI: 75.4–94.1%) and 80.4% (95% CI: 67.6–89.8%), in the whole group and those with past history of tuberculosis, respectively. Conclusions: LDBio LFA is a point-of-care test with reasonable sensitivity and specificity. However, further tests may have to be done to rule-in or rule-out the diagnosis of CPA in the appropriate setting. [ABSTRACT FROM AUTHOR]

Objective: The objective was to study the sensitivity, specificity, and diagnostic accuracy of various computed tomography (CT) chest findings in diagnosing recurrence among pulmonary tuberculosis (PTB) suspects. Materials and Methods: A prospective observational study was conducted in a tertiary care hospital in New Delhi. A total of 130 suspects with a past history of treatment for PTB, who presented with any of the symptoms suggestive of recurrence were included. Sputum-positive, HIV-positive patients, pregnant females, and patients aged <18 years were excluded. Patients underwent CT chest followed by bronchoalveolar lavage (BAL). Results: A total of 62 patients were there in the final analysis. The median age of the patients with recurrent PTB was 27.5 years. Cough was the universal symptom in all these patients (>90%). Hemoptysis was the predominant symptom among patients with chronic pulmonary aspergillosis (66.6%). Necrotic mediastinal lymph nodes had good diagnostic accuracy of 88.71% with area under the curve of 0.806, P < 0.001 in diagnosing recurrent TB. BAL GeneXpert and mycobacteria growth indicator tube had good sensitivity (83.33% and 84.62%, respectively), specificity (100% for both), and excellent diagnostic accuracy (95.16% and 96.36%, respectively) for diagnosing recurrence in sputum negative and sputum scarce patient, (P < 0.001) when compared with composite reference standard. For culture-positive cases, BAL GeneXpert MTB/RIF had 100% sensitivity and 97.73% specificity in diagnosing recurrent PTB patients. Conclusion: The presence of mediastinal necrotic lymph node is the most accurate CT finding that can differentiate recurrent TB from post-TB sequelae. No other single chest CT scan finding had reliable diagnostic accuracy in comparison to microbiological tools in diagnosing recurrence among sputum negative or scarce previously treated PTB suspects. [ABSTRACT FROM AUTHOR]

Background: Though invasive pulmonary aspergillosis is a well known complication of COVID‐19 pneumonia, indolent forms of aspergillosis have been rarely described. Methods: We prospectively collected the clinico‐radio‐microbiological data of 10 patients of subacute invasive pulmonary aspergillosis (SAIA), who presented to our hospital with recent history of COVID‐19 pneumonia along with cavitary lung disease, positive IgG (against Aspergillus) with or without positive respiratory samples for Aspergillus spp. Result: The mean age of presentation of SAIA was 50.7 ± 11.8 years. All the patients had recently recovered from severe COVID‐19 illness with a mean duration of 29.2 ± 12 days from COVID‐19 positivity. Cough was the predominant symptom seen in 8/10 (80%) patients followed by haemoptysis. 7/10 (70%) patients were known diabetic. While serum galactomannan was positive in 5/9 patients (55.5%), fungal culture was positive in 2/7 patients (28.5%) and polymerase chain reaction (PCR) for Aspergillus was positive in three patients. Eight (80%) patients presented with a single cavitary lesion; pseudoaneurysm of pulmonary artery was seen in two patients and post‐COVID‐19 changes were seen in all patients. All patients were treated with voriconazole, out of which four (40%) patients died during the follow‐up period. Conclusion: SAIA should be considered in the differential diagnosis of cavitating lung lesions in patients with recent history of COVID‐19 in the background of steroid use with or without pre‐existing diabetes. [ABSTRACT FROM AUTHOR]

Global literature examining the association between mental health of women living with HIV (WLWH) and child development is scarce. In this study, we examined the relationship between mothers' mental health and their children's social development outcomes 6 months later. Data for these analyses come from several waves of interviews of 600 WLWH in the South Indian state of Andhra Pradesh, India. These women were enrolled in a 2 × 2 factorial clinical trial designed to assess the impact of food supplementation and nutrition education, both in addition to ASHA support, on adherence to ART and improved health outcomes for the women and one of their children. They were assessed on food security, stigma, social support, quality of life, depressive symptoms and child development outcomes. Results of longitudinal GEE regression analysis indicate that mother's depressive symptoms were significantly negatively associated with child's social quotient 6 months later. These findings have important implications for targeted health interventions, integrating mental health, both for WLWH and their children in India. [ABSTRACT FROM AUTHOR]

Background & objectives: HIV/AIDS patients may have renal involvement also, however, Indian data are sparse. The present study was done to find the spectrum of renal diseases in HIV/AIDS patients in north India. Methods: In this prospective pilot study, HIV positive patients aged >18 yr were screened for renal involvement [serum creatinine >1.5 mg% and/or significant proteinuria (>500 mg /day)]. Patients who were positive on screening were followed up prospectively and underwent kidney biopsy if indicated. Results: A total of 526 patients were screened, of these, 91 (17.3%) were found to have renal involvement. Group A (Treatment naïve) comprised 392 patients who were not on antiretroviral treatment (ART) and group B (patients on ART) comprised 134 patients. More patients (74/392, 18.9%) in group A had renal involvement as compared to patients in group B (17/134, 12.7%). Of the 91 patients with renal involvement, 26 were followed up and underwent kidney biopsy. Thirteen patients had only proteinuria and another 13 had renal dysfunction with or without proteinuria. Most common histological diagnosis was mesangioproliferative glomerulonephritis (mes PGN) (10/26). Two patients had collapsing FSGS (focal segmental glomerulosclerosis) and three patients had immune complex glomerulonephritis. Seven patients had acute kidney injury, whom six totally recovered from their renal function. All patients with mesPGN tolerated angiotensin converting enzyme (ACE) inhibitors well. There was mixed response of collapsing FSGS to steroids. Both patients with MPGN (membranoproliferative glomerulonephritis) did well on low dose of steroid and ART. Interpretation & conclusions: Renal involvement was found to be common in HIV positive patients (17.3%). A low occurrence of renal involvement found in patients already on ART suggests some renoprotective effect of ART. Our preliminary results showed that collapsing FSGS was not rare in Indian HIV positive population, but classical HIV associated nephropathy was not seen. Longitudinal studies with robust study design and large sample size need to be done to confirm the findings. [ABSTRACT FROM AUTHOR]

Background: Pulmonary aspergilloma (PA) is a common complication seen in patients with pulmonary tuberculosis sequelae. Antifungal therapy, including oral azoles, is commonly used though only surgical resection offers curative benefit. Local administration of amphotericin B, like intracavitary instillation, has been effective in aspergilloma patients though nebulised amphotericin B (nAB) has never been formally assessed. Objective: The aim of this prospective, non‐inferior, open‐label, randomised control trial is to evaluate the efficacy and safety of nebulised amphotericin B compared to oral itraconazole therapy in the treatment of PA. Patients/Methods: Diagnosed cases of PA (n=33) were randomised into the control group receiving oral itraconazole (n=18) and intervention group receiving nebulised amphotericin B (n = 15). Response to treatment was assessed both clinically and radiologically at the end 6 months. Results and Conclusion: The number of patients showing overall improvement at the end of 6 months in the control arm(oral itraconazole) vs intervention arm(nebulised amphotericin B) was 65% (95% CI 38.3–85.8) and 67%(95% CI 38.4%–88.2%), respectively, in the intention‐to‐treat and 79% (95% CI 49.2%–95.3%), and 65% (95% CI 38.4%–88.2%), respectively, in the per‐protocol analysis. While there was no statistically significant difference between the intervention and control arm in both the analyses, non‐inferiority was shown in the per‐protocol but not in the intention‐to‐treat analysis. No major adverse events were noted in either group; however, a significant proportion of patients receiving nAB reported minor cough (40%), which, however, did not lead to discontinuation of therapy in any patients. Nebulised amphotericin B can be an effective therapeutic option for pulmonary aspergilloma patients. [ABSTRACT FROM AUTHOR]

Background: Currently, there is no data on the impact of COVID-19 on patients' income and work in India. Methods: We conducted a cross-sectional study at a tertiary hospital in New Delhi. We included all the patients who were ≥18 years of age and consecutively diagnosed with COVID-19 between the 1st of May 2020 to 31st July 2020. Patients were interviewed by a physician using a semi-structure questionnaire. Data were collected on socio-economic status, occupation, income loss, leaves taken, decrease in work efficiency (self-perceived) and about-facing any stigma/discrimination at the workplace. Results: Out of 245 patients, 190 patients were employed. A total of 126 patients (66.3%) self-reported their work was affected due to COVID-19 disease. A total of 30.5% of patients (n = 58/190) reported deduction in their salary. The median amount of salary loss was INR 10,000 (IQR 9000–25000). Decrease in income and work efficiency (self-perceived) was found to be 37.3% (n = 71) and 12.1% (n = 23), respectively. A total of 47 patients (37.3%) took personal leaves (median number – 17 days (IQR 14–25), and discrimination/stigma related to the COVID-19 at the workplace was faced by 22.6% of patients. Conclusion: Income and work of a substantial number of patients was affected due to COVID-19, as there was a decrease in income and work efficiency. Patients also had to take personal leaves and face stigma in the workplace. This will inform the policymakers to formulate strategies to mitigate the impact of COVID-19. [ABSTRACT FROM AUTHOR]

The article offers information on the role of Empagliflozin Outcome Trial in Patients with Chronic Heart Failure and a Reduced Ejection Fraction. It mentions that empaglif1ozin was associated with a lower risk than placebo of a composite outcome of cardiovascular death or hospitalization for heart failure among patients who had heart failure with reduced ejection fraction.

Background: Obstructive sleep apnoea (OSA) is an important factor in the development and progression of heart failure (HF). The prevalence of OSA is higher in patients with HF than in the general population. We sought to test the hypothesis that OSA severity was predictive of ventricular function and cardiac injury [as assessed by high-sensitivity cardiac troponin I(hs-cTnI)].Methods: A total of 60 patients were recruited after evaluation for sleep disturbances using the Jenkins Sleep Questionnaire (JSQ) and Epworth Sleepiness Scale (ESS). Subsequently, they underwent polysomnography thus confirming the diagnosis of OSA and were equally divided into three groups according to OSA severity grade. Following polysomnography, the next morning patients underwent venous blood sampling and echocardiography.Results: We observed a statistically significant association (P = 0.009) between diastolic dysfunction grades and severity grades of OSA. All the three diastolic dysfunction variables E/A ratio, deceleration time and E/e' ratio had a significant association(P < 0.05) with severity grades of OSA. There was a marginally significant positive correlation (ρ = 0.3244, p = 0.04) between AHI events per hour and mitral E/e' ratio. There was a statistically significant association(P < 0.001) between hs-cTnI value among different severity grades of OSA.Conclusions: Here in our study, we found OSA a potential risk factor for development of myocardial injury and diastolic dysfunction. Severe grades of OSA are associated with higher grades of diastolic dysfunction and circulating levels of hs-cTnI. These data are consistent with the notion of a vicious cycle of frequent apnoea's or hypoxemia and recurrent myocardial injury, which could increase the risk of heart failure especially diastolic dysfunction in OSA. [ABSTRACT FROM AUTHOR]

To evaluate Gene Xpert for diagnosis of Female Genital Tuberculosis (FGTB) as compared to conventional methods.Study Design: It was a prospective study conducted over 167 cases of infertile female genital tuberculosis (FGTB) diagnosed on composite reference standard (CRS) (smear for AFB, histopathological evidence of epithelioid granuloma or definite or possible findings of tuberculosis on laparoscopy). All women underwent endometrial biopsy for AFB microscopy, culture, gene Xpert, PCR and histopathology) and laparoscopy and hysteroscopy for diagnosis and prognostication of disease. The results of Gene Xpert were compared with conventional methods in detection of FGTB. All patients were treated with 6 months course of rifampicin (R), isoniazid (H), pyrazinamide (Z) and ethambutol (E) (RHZE for 2 months, RHE for 4 months) using directly observed treatment short course strategy.Results: Mean age, parity, body mass index and history of contact was 28.3 years, 0.28, 22.9 Kg/m2 and 38.92% respectively. Primary infertility was seen in 87.42% cases with mean duration of 2.42 years. Menstrual dysfunctions, abdominal or pelvic pain and lump were seen in 38.92%, 14.37% and 10.77% cases. Abnormal vaginal discharge and adnexal mass were seen in 28.14% and 13.17 % cases. On diagnostic laparoscopy, definite findings of tuberculosis (beaded tubes, tuebrcles and caseous nodules) were seen in 96 (57.48%) women while probable findings of tuberculosis (pelvic or abdominal adhesions, hydrosaplinx, tubo-ovarian mass, pyosalpinx) were seen in 81 (48.50%) women. On laboratory investigations, positive AFB on microscopy or culture was seen in 2.99% casess, PCR was positive in 47.90% gene Xpert was positive in 18.56% cases while epitheloid granuloma was seen on histopathology in 16 (9.58%) cases. Gene Xpert had sensitivity of 35.63%, specificity of 100%, positive predictive value of 100% and negative predictive value of 58.82% and diagnostic accuracy of 66.47% in the present study.Conclusion: Gene Xpert is a very useful test to rule in tuberculosis whereas when it is negative it is not a good test to rule out tuberculosis. [ABSTRACT FROM AUTHOR]

Background Malnutrition is a common clinical concern among children in low-income communities affected by human immunodeficiency virus (HIV). We examined the effect of a community-based nutritional intervention on anthropometric and clinical outcomes of children of women living with HIV in rural India. Methods We assigned women living with HIV and their child (oldest 3–8 years) to 1 of 4 programs: (1) community-based HIV care program, (2) program 1 + nutrition education, (3) program 1 + food supplement, and (4) all elements of programs 1–3. Study data were collected at baseline and months 6, 12, and 18. We applied mixed-effects modeling with restricted maximum likelihood estimation to examine changes in weight (all children) and CD4+ T-cell counts (children with HIV only). Results Overall, 600 mother–child pairs were enrolled (150/group) with 100% retention at follow-up visits. Approximately 20% of children were living with HIV. Children in program 4 had higher weight gain than those in programs 1, 2, and 3 at all time points (adjusted P <.001). We found a higher increase in CD4+ T cells across all time points among participants in programs 3 and 4 compared with program 1 (adjusted P <.001). Factorial analysis suggested a synergistic effect of combining nutrition education and food supplements for weight gain but not for increase in CD4+ T cells. Conclusions A combination of nutrition education and food supplements provided to women living with HIV significantly increased weight and CD4+ T cells, and such interventions can be integrated into HIV-care programs in low-income settings. [ABSTRACT FROM AUTHOR]