Global epidemiological burden of fungal infections in cirrhosis patients: A systematic review with meta-analysis.

BACKGROUND AND AIMS: Fungal infections (FIs) have serious implications, yet understated in cirrhosis. Therefore, we reviewed the epidemiology and trends of FIs among cirrhotics. METHODS: Four electronic databases were searched for full-text articles describing prevalence of FIs in cirrhosis. Studies from post-transplant, malignancy and classical-immuno-deficiency patients were excluded. A random-effects meta-analysis was done to pool estimates of FIs (overall, and by type and infection-site), and their variation(I2 ) was explored on moderator-analysis and meta-regression. Risk of bias and asymmetry in estimates was assessed by a checklist and Egger's regression, respectively.(CRD42019142782). RESULTS: Thirty-four low-risk and four moderate-risk studies (31 984 cirrhotics) were included. Pooled estimates of overall FIs (17 studies), invasive fungal infections (IFIs; 17 studies), invasive candidiasis (23 studies) and invasive aspergillosis (16 studies) in cirrhosis were 10.2%(6.0-16.9), 9.5%(5.4-16.2), 4.0%(2.0-8.0) and 2.8%(1.5-5.3), respectively (I2  > 90%;each). Site of FIs in decreasing order of pooled prevalence was pulmonary, urinary tract, bloodstream, peritoneal, oesophageal and cerebral. Geographic differences in these estimates were remarkable, with highest burden of overall FIs from Belgium, the United States and India. Non-albicans-Candida and Aspergillus infections have increased over the last decade in cirrhosis. Intensive-care-unit (ICU)-admitted and acute-on-chronic liver failure (ACLF) patients had the highest prevalence of IFIs. MELD score(cases), bias score and sample size across studies were the predictors of variance in overall FI estimates. Diabetes, steroid and broad-spectrum antibiotic-exposure, and multiple organ failures were the common predispositions reported in patients with FIs. CONCLUSIONS: FIs impose a substantial burden in cirrhosis. ACLF and ICU admission should be considered as a host factor for defining IFIs. Epidemiology of FIs can guide interpretation of biomarkers and antifungal treatment in cirrhosis.

The perceived need for evidence-based COVID-19 management and Tele-education in the North-East region of India: a cross-sectional survey.

Due to the sudden rise in the cases of COVID-19 in the North-Eastern region of India, this study was conducted to survey the felt needs of the medical professionals with regards to education on the evidence-based management of COVID-19. A total of 25 North-East leaders were recruited and a baseline survey was conducted through the digital medium. Out of 25 North-East leaders, 52% were undergoing training in evidence-based medicine in the capacity-building program for evidence-based child health. Participants (48%) strongly agreed and 40% agreed on the possibility of enhanced care by capacity building in the areas of COVID-19 management through discussing cases. Out of 25 North East leaders, 48% agreed to join both as a speaker as well as a participant. Various priority topics on COVID-19 management e.g. childhood, adult, ocular manifestation, ICU management, telemedicine, vaccines, lab protocols, psychological distress, and treatment strategy have emerged. We have presented the findings of the survey which will help guide the mentoring program focusing on evidence-based management of COVID-19 in remote areas through Tele-education.

Effect of Probiotics on the Frequency of CD4+ T-Cells in HIV-Infected Children and Adolescents: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

BACKGROUND: Depletion of CD4+ T-cells in the gut-associated lymphoid tissue is the hallmark of HIV infection, with only partial restoration by potent antiretroviral therapy (ART). Gut dysbiosis, together with disruption of mucosal integrity contributes to chronic immune activation that further exacerbates the disease. Data from randomized controlled trials in pediatric HIV patients have indicated potential of probiotics in complementing routine ART in managing HIV-associated gastrointestinal complications. We have systematically extracted data from these trials and performed meta-analysis to quantify the effect of probiotics on CD4+ T-cell counts and any adverse events associated with their supplementation. METHODS: A systematic search through multiple databases yielded three studies that were pooled using fixed-effect model. Risk of bias assessment was done by the Cochrane risk of bias tool and publication bias was assessed by Egger's test. RESULTS: Included studies had moderate risk of bias and Egger's statistics revealed no publication bias (p > 0.05). Pooled analysis showed significant improvement in CD4+ T-cell counts, with mean difference, 123.92 (95% CI: 104.36-143.48), p < 0.0001, no heterogeneity (I2=0) among the included trials. Subgroup analysis also depicted improvement in CD4+ T-cell counts irrespective of treatment duration, in both ART naïve and treated patients. No adverse effects with probiotic consumption were reported. CONCLUSIONS: Probiotics supplementation led to an improvement in CD4+ T-cell counts among HIV-infected children with no observed adverse effects. Despite the inherent limitations of included studies, our systematic review would justify more well-designed, large-scale trials in children, which may guide pediatricians on whether to incorporate probiotics as an adjunct therapy to routine ART.

HIV infection is associated with a progressive decline of CD4+ T-cell numbers and increase in viral load. To keep the virus replication in check, patients need to take the antiretroviral therapy life-long, which is not without gastrointestinal discomfort. Probiotics have already shown multiple benefits ranging from reduction in diarrhea, nausea and bloating besides replenishment of CD4+ T-cells numbers. Based on this background information, we have compiled the data on probiotics among HIV-infected children. A pooled analysis from randomized clinical trials revealed significant improvement in CD4+ T-cell counts in HIV-infected children without any adverse effects. However, we recommend large and well-designed trials in future that would help in forming a concrete and high quality evidence in this context.

Identification of Mtb GlmU Uridyltransferase Domain Inhibitors by Ligand-Based and Structure-Based Drug Design Approaches.

Targeting enzymes that play a role in the biosynthesis of the bacterial cell wall has long been a strategy for antibacterial discovery. In particular, the cell wall of Mycobacterium tuberculosis (Mtb) is a complex of three layers, one of which is Peptidoglycan, an essential component providing rigidity and strength. UDP-GlcNAc, a precursor for the synthesis of peptidoglycan, is formed by GlmU, a bi-functional enzyme. Inhibiting GlmU Uridyltransferase activity has been proven to be an effective anti-bacterial, but its similarity with human enzymes has been a deterrent to drug development. To develop Mtb selective hits, the Mtb GlmU substrate binding pocket was compared with structurally similar human enzymes to identify selectivity determining factors. Substrate binding pockets and conformational changes upon substrate binding were analyzed and MD simulations with substrates were performed to quantify crucial interactions to develop critical pharmacophore features. Thereafter, two strategies were applied to propose potent and selective bacterial GlmU Uridyltransferase domain inhibitors: (i) optimization of existing inhibitors, and (ii) identification by virtual screening. The binding modes of hits identified from virtual screening and ligand growing approaches were evaluated further for their ability to retain stable contacts within the pocket during 20 ns MD simulations. Hits that are predicted to be more potent than existing inhibitors and selective against human homologues could be of great interest for rejuvenating drug discovery efforts towards targeting the Mtb cell wall for antibacterial discovery.

Effectiveness-of Calcium Phosphate derivative agents on the prevention and remineralization of caries among children- A systematic review & meta-analysis of randomized controlled trials.

OBJECTIVES: Dental caries among children is a highly prevalent yet easily preventable oral health issue among children. Various calcium phosphate (CaP) derivatives are implicated to exhibit caries preventive potential; however, no study has summarized the anti-caries effectiveness of these agents. This systematic review and meta-analysis sought to assess the caries-preventive and tooth-remineralizing effect of various (CaP) derivative agents compared to no-intervention/placebo or Fluoride (F) use alone among children. MATERIALS AND METHODS: EMBASE, Ovid, PubMed, Scopus, Web of Science, Cochrane central register of controlled trials (CENTRAL), and grey literature were searched for relevant articles up to April 2021. Only English-language articles were included. Total 2636 articles were searched through different databases; out of the 2161 articles were screened after duplicate removal. 26 studies fulfilling the eligibility criteria were included in this systematic review. Methodological quality assessment and quantitative analysis were done using RevMan. GRADE was used to evaluate the certainty of evidence. RESULTS: A total of 26 trials fulfilling the eligibility criteria were included. The meta-analysis of 10 studies revealed that complete white spot lesions (WSLs) regression (RR=1.56; 95% CI, 1.27 to 1.91; P < .0001, I2=0%), post intervention active WSLs (RR=0.80; 95% CI, 0.70 to 0.90; P = .0004, I2=0%) and post intervention Salivary S. mutans count (RR= 0.69; 95% CI, 0.48 to 0.99; P = .47, I2=0%) significantly favored the CaP+F combined therapy as compared to F alone. No significant differences in the lesion area, Delta F, and DIAGNOdent values were observed between the 2 groups. Low certainty of the evidence was found in the present systematic review due to the high/unclear risk of bias, imprecision, and indirectness of included trials. CONCLUSIONS: Topical treatment using CaP+F group showed superior remineralization potential as well as the antibacterial effect on dental caries among children as compared to no intervention and/or placebo or F alone. Apart from CPP-ACP, other CaP derivatives like TCP and fTCP seem to have promising effects in remineralizing early lesions, however, very few trials exist on these potential agents. To provide definitive recommendations in this area, more clinical trials on caries preventive effectiveness of various CaP agents are warranted.

Invasive aspergillosis is a critical determinant of mortality in cirrhosis: a systematic review with meta-analysis.

Invasive fungal infections pose a severe threat in unconventional immunocompromised hosts such as cirrhosis. Herein we review the impact of invasive aspergillosis (IA) on the prognosis of cirrhosis patients. An electronic search for full-text articles describing IA in cirrhosis was conducted and the disease outcomes and mortality (point-estimate and comparative risk) were pooled on random-effects meta-analysis. Of 4127 articles, 11 studies (9 with good/fair and 2 with poor quality) were included. IA was associated with high disease severity and multi-organ failures in cirrhosis. The pooled-mortality of IA was 81.8% (95% CI: 64.3-91.8, I2 = 59%, P < 0.01). Estimate's-heterogeneity (I2) was explored through sub-groups, meta-regression, and influential diagnostics. Mortality estimates were higher among subgroups of acute-on-chronic liver failure (ACLF, 86.4%) and intensive care unit (ICU)-admitted patients (84.0%). The odds of mortality related to IA were 8.9 times higher than controls and much higher in ACLF (OR: 22.5) and ICU-admitted patients (OR: 36.4). The odds of mortality in IA were 4.1, 12.9, and 48.6 times higher than bacterial, no-fungal infections, and no-infection controls. There was no asymmetry in mortality estimates or odds ratios and mortality in IA was high irrespective of country of origin, site of infection, proven or probable category, and quality of study. Thus, IA is associated with very high mortality in cirrhosis patients, especially in ACLF and ICU-admitted patients. Intensive research is needed for the rapid diagnosis and treatment of IA in cirrhosis. LAY SUMMARY: We report a high mortality rate of 81.8% in patients with liver cirrhosis and invasive aspergillosis. Higher odds (8.9 times) of death, especially in patients with ACLF or ICU admission were seen. Mortality was not affected by the country of study, site of infection, proven or probable nature of infection category, and quality of study.

Comparative accuracy of 1,3 beta-D glucan and galactomannan for diagnosis of invasive fungal infections in pediatric patients: a systematic review with meta-analysis.

Invasive fungal infections (IFI) cause considerable morbidity and mortality in pediatric patients. Serum biomarkers such as 1,3-beta-D glucan (BDG) and galactomannan (GM) have been evaluated for the IFI diagnosis. However, most evidence regarding their utility is derived from studies in adult oncology patients. This systematic review aimed to compare the diagnostic accuracy of BDG and GM individually or in combination for diagnosing IFI in pediatric patients. PubMed, CINAHL, Embase, and Cochrane Library were searched until March 2019 for diagnostic studies evaluating both serum GM and BDG for diagnosing pediatric IFI. The pooled diagnostic odds ratio (DOR), specificity and sensitivity were computed. Receiver operating characteristics (ROC) curve and area under the curve (AUC) were used for summarizing overall assay performance. Six studies were included in the meta-analysis. The summary estimates of sensitivity, specificity, pooled DOR, AUC of the GM assay for proven or probable IFI were 0.74, 0.76, 13.25, and 0.845. The summary estimates of sensitivity, specificity, pooled DOR, AUC of the BDG assay were 0.70, 0.69, 4.3, and 0.722. The combined predictive ability of both tests was reported in two studies (sensitivity: 0.67, specificity: 0.877). Four studies were performed in hematology-oncology patients, while two were retrospective studies from pediatric intensive care units (ICUs). In the subgroup of hematology-oncology patients, DOR of BDG remained similar at 4.25 but increased to 40.28 for GM. We conclude that GM and BDG have a modest performance for identifying IFI in pediatric patients. GM has a better accuracy over BDG. Combining both improves the specificity at the cost of sensitivity.

Association of Serum TGF-ß1 Levels with Different Clinical Phenotypes of Cystic Fibrosis Exacerbation.

PURPOSE: Cystic Fibrosis (CF) is a multi-organ genetic disorder and Transforming Growth Factor (TGF-ß1) is a modifier gene which modulates lung pathology in CF. There is great phenotypic variability among CF patients who even have similar genotype. The aim of the present study was to associate the serum levels of TGF-ß1 with several clinical phenotypes of CF. METHODS: The diagnosed cases of CF were recruited and the blood sample was withdrawn at different time points: during exacerbation (n = 26), non-exacerbation (n = 9) and after antibiotic therapy (n = 11). The concentration of the total TGF-ß1 in serum was measured with commercial ELISA kit. The ΔF508 mutation was assessed by the Amplification Refractory Mutation System (ARMS-PCR). RESULTS: The levels of TGF-ß1 were increased in exacerbation phase (119.89 ± 29.64 ng/mL), infection with P. aeruginosa (121.8 ± 28.83 ng/mL) and in subjects with ΔF508 mutation (139.2 ± 19.59 ng/mL). The levels of TGF-ß1 in CF patients with Allergic Bronchopulmonary Aspergillosis (ABPA) (109.97 ± 27.71 ng/mL) were decreased as compared to CF patients without ABPA (123.55 ± 30.20 ng/mL). It was observed that the serum levels of TGF-ß1 were decreased significantly after antibiotic therapy (p < 0.05). CONCLUSIONS: The present study has determined that the serum levels of TGF-ß1 vary with the type of infections, ΔF508 CFTR mutation, presence of ABPA and response to therapy.

Design of expert guided investigation of native L-asparaginase encapsulated long-acting cross-linker-free poly (lactic-co-glycolic) acid nanoformulation in an Ehrlich ascites tumor model.

Present study explores native L-asparaginase encapsulated long-acting cross-linker-free PLGA-nanoformulation in an Ehrlich ascites tumor model. L-asparaginase-PLGA nanoparticles for tumor were prepared using a double emulsion solvent evaporation technique, optimized and validated by Box-Behnken Design. L-ASN-PNs showed a particle size of 195 nm ± 0.2 nm and a PDI of 0.2. Scanning Electron Microscopy (SEM) and Transmission Electron Microscopy (TEM) techniques revealed its smooth morphology and elicited an in-vitro release of 80% of the drug, following the Higuchi drug release model. In-vivo studies of L-ASN-PNs on an Ehrlich ascites tumor (EAT) model were completed and compared with the standard medication of 5-fluorouracil (5-FU) treatment. L-ASN-PN treated mice showed a 51.15% decrease in tumor volume and 100% survival rate with no reduction in body weight, no haemotoxicity and no hepatotoxicity, as evident from the hematological parameters, and liver enzyme parameters that were well within the prescribed limits. Chemotherapy has severe side effects and restricted therapeutic success. Henceforth, the purported L-Asparaginase PLGA nanoparticles are a suitable entity for better tumor regression, intra-tumor accumulation and no hematological side-effects.

Need to re-look cut-off of Aspergillus-specific IgE levels in children with ABPA.

The cut-offs for total and specific IgE used for diagnosing ABPA in children have been adopted from adult literature and have not been validated in the paediatric population. To establish the ideal cut-offs of total IgE and Aspergillus-specific IgE for the diagnosis of ABPA in children. This study was a prospective observational case-control study, conducted in a tertiary care hospital in North India, enrolling 140 children with partly controlled and uncontrolled asthma. Seventy children had ABPA based on the Rosenberg-Patterson Criteria (Cases) whereas 70 children were without ABPA (Controls). All children were subjected to clinical examination and investigations such as absolute eosinophil count, total IgE, Aspergillus-specific IgE, Aspergillus skin prick test and radiological tests. ROC curve analysis was done to determine the ideal cut-offs of total and specific IgE to diagnose ABPA. The ROC curve analysis determined 1204IU/L as the cut-off value of total IgE with a sensitivity of 79.7% (95%CI 68.31% to 88.44%) and specificity of 53.1% (95%CI 40.23 to 65.7). The ROC analysis of specific IgE levels of children with ABPA determined the cut-off value of 0.49 KAU/L with a sensitivity of 94.03% (95%CI 85.41 to 98.35) and specificity of 88.89% (95%CI 75.94% to 96.29%). We propose that the cut-offs of total and specific IgE need to be relooked in the paediatric population. Cut-offs of total IgE as 1204 IU/L and for Aspergillus-specific IgE as 0.49KAU/L seem appropriate. Large multicentric studies should be conducted to determine the ideal values for diagnosing paediatric ABPA.

Novel nicotinamide analog as inhibitor of nicotinamide N-methyltransferase.

Nicotinamide N-methyltransferase (NNMT) has been linked to obesity and diabetes. We have identified a novel nicotinamide (NA) analog, compound 12 that inhibited NNMT enzymatic activity and reduced the formation of 1-methyl-nicotinamide (MNA), the primary metabolite of NA by ∼80% at 2 h when dosed in mice orally at 50 mg/kg.

Heated, humidified air for the common cold.

BACKGROUND: Heated, humidified air has long been used by people with the common cold. The theoretical basis is that steam may help congested mucus drain better and that heat may destroy the cold virus as it does in vitro. This is an update of a review last published in 2013. OBJECTIVES: To assess the effects of inhaling heated water vapour (steam) in the treatment of the common cold by comparing symptoms, viral shedding, and nasal resistance. SEARCH METHODS: We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (to February 2017), MEDLINE (1966 to 24 February 2017), Embase (1990 to 24 February 2017), and Current Contents (1998 to 24 February 2017). We also searched World Health Organization International Clinical Trials Registry Platform (WHO ICTRP) (8 March 2017) and ClinicalTrials.gov (8 March 2017) as well as reference lists of included studies. SELECTION CRITERIA: Randomised controlled trials using heated water vapour in participants with the common cold or experimentally induced common cold were eligible for inclusion. DATA COLLECTION AND ANALYSIS: We used standard methodological procedures expected by Cochrane. Three review authors independently screened titles and abstracts for inclusion of potential studies identified from the search. We recorded the selection process in sufficient detail to complete a PRISMA flow diagram. We used a data collection form for study characteristics and outcome data that was developed and used for previous versions of this review. Two review authors independently extracted data, and a third review author resolved any disagreements. We used Review Manager 5 software to analyse data. MAIN RESULTS: We included six trials from five publications involving a total of 387 participants. We included no new studies in this 2017 update. The 'Risk of bias' assessment suggested an unclear risk of bias in the domain of randomisation and a low risk of bias in performance, detection, attrition, and reporting.It was uncertain whether heated, humidified air provides symptomatic relief for the common cold, as the fixed-effect analysis showed evidence of an effect (odds ratio (OR) 0.30, 95% confidence interval (CI) 0.16 to 0.56; 2 studies, 149 participants), but the random-effects analysis showed no significant difference in the results (OR 0.22, 95% CI 0.03 to 1.95). There is an argument for using either form of analysis. No studies demonstrated an exacerbation of clinical symptom scores. One study conducted in the USA demonstrated worsened nasal resistance, but an earlier Israeli study showed improvement. One study examined viral shedding in nasal washings, finding no significant difference between treatment and placebo groups (OR 0.47, 95% CI 0.04 to 5.19). As judged by the subjective response to therapy (i.e. therapy did not help), the number of participants reporting resolution of symptoms was not significantly higher in the heated humidified group (OR 0.58, 95% CI 0.28 to 1.18; 2 studies, 124 participants). There was significant heterogeneity in the effects of heated, humidified air on different outcomes, therefore we graded the quality of the evidence as low. Some studies reported minor adverse events (including discomfort or irritation of the nose). AUTHORS' CONCLUSIONS: The current evidence does not show any benefits or harms from the use of heated, humidified air delivered via the RhinoTherm device for the treatment of the common cold. There is a need for more double-blind, randomised trials that include standardised treatment modalities.

Mapping of arsenic pollution with reference to paddy cultivation in the middle Indo-Gangetic Plains.

A detailed field study was carried out to monitor (i) the arsenic contents in irrigation groundwater and paddy soil and (ii) the accumulation of arsenic in the roots and grains of different paddy varieties grown in the arsenic-contaminated middle Indo-Gangetic Plains of Northern India. Results showed the highest arsenic contamination in the irrigation groundwater (312 µg l(-1)) and in paddy soil (35 mg kg(-1)) values that were significantly exceeded the recommended threshold values of 100 µg l(-1) (EU) and 20 mg kg(-1) (FAO), respectively. The paddy soil arsenic content ranged from 3 to 35 mg kg(-1) with a mean value of 15 mg kg(-1). The soil arsenic content was found to be influenced by the soil texture, carbon, macronutrients, phosphorus, sulfur, hydrolases, and oxidoreductases properties of the paddy soils as revealed in the principal component analyses. Higher root accumulation (>10 mg kg(-1)) of arsenic was observed in 6 of the 17 paddy varieties grown in the study area. The range of arsenic content accumulated in the paddy roots was 4.1 to 16.2 mg kg(-1) dry weight (dw) and in the grains 0.179 to 0.932 mg kg(-1) dw. Out of 17 paddy varieties, eight had 0 > .55 mg kg(-1) grain arsenic content and were found unsafe for subsistence maximum daily tolerable dietary intake (MTDI) by human beings according to the regulatory standards.

Effect of Hydroxychloroquine and Azithromycin Combination Use in COVID-19 Patients - An Umbrella Review.

Background: Hydroxychloroquine and Azithromycin combination was used rampantly in management of COVID-19 patients in different countries. Present review was conducted to evaluate the efficacy of Hydroxychloroquine and Azithromycin combination compared to the control (standard care) and any adverse effect following this combination use in COVID-19 patients if any. Material and Methods: We included all the systematic review with or without meta-analysis reporting the effect of Hydroxychloroquine (HCQ) and Azithromycin (AZM) combination use in COVID-19 patient using three databases namely PubMed, medline, CINHAL, Web of Science from July 2020 till Jan 2022. Results: The systematic search strategy has identified 104 studies in total, after removal of duplicates only 4 systematic reviews were included in the qualitative synthesis. The various tools for assessing and reporting the data in the reviews were PRISMA, ROBINS-I, Robs2, AMSTAR, MASTER checklists. Mortality among the hydroxychloroquine with azithromycin combination group was significantly higher than among the Standard Care group. The duration of hospital stay in days was shorter in the Standard Care group in comparison with the hydroxychloroquine group or the hydroxychloroquine and azithromycin combination group. Of the 4 systematic reviews included, 3 had low risk of bias and one had unclear risk of bias using the ROBIS tool. Chloroquine or Hydroxychloroquine combination did not shorten the duration of hospital stay. Conclusion: Rampant use of Chloroquine or Hydroxychloroquine alone or with Azithromycin combination caused adverse effects like QT prolongation. Finally, there is no evidence to support use of either Hydroxychloroquine with or without Azithromycin, for the treatment of COVID-19.

Heated, humidified air for the common cold.

BACKGROUND: Heated, humidified air has long been used by sufferers of the common cold. The theoretical basis is that steam may help congested mucus drain better and heat may destroy the cold virus as it does in vitro. OBJECTIVES: To assess the effects of inhaling heated water vapour (steam) in the treatment of the common cold by comparing symptoms, viral shedding and nasal resistance. SEARCH METHODS: In this updated review we searched CENTRAL 2013, Issue 2, MEDLINE (1966 to February week 4, 2013), EMBASE (1990 to March 2013) and Current Contents (1994 to March 2013). SELECTION CRITERIA: Randomised controlled trials (RCTs) using heated water vapour in participants with the common cold or participants with experimentally induced common cold. DATA COLLECTION AND ANALYSIS: The two review authors independently reviewed all retrieved articles and excluded any articles, editorials and abstracts with inadequate outcome descriptions. The studies we included were subjected to a methodological assessment. MAIN RESULTS: We included six trials (394 trial participants). Three trials in which patient data could be pooled found benefits of steam for symptom relief for the common cold (odds ratio (OR) 0.31; 95% confidence interval (CI) 0.16 to 0.60). However, results on symptom indices were equivocal. No studies demonstrated an exacerbation of clinical symptom scores. One study conducted in the USA demonstrated worsened nasal resistance, while an earlier Israeli study showed improvement. One study examined viral shedding and antibody titres in nasal washings; there was no change in either between treatment and placebo groups. Minor side effects (including discomfort or irritation of the nose) were reported in some studies. AUTHORS' CONCLUSIONS: Steam inhalation has not shown any consistent benefits in the treatment of the common cold, hence is not recommended in the routine treatment of common cold symptoms until more double-blind, randomised trials with a standardised treatment modality are conducted.

Development and Characterization of Terbinafine-Loaded Nanoemulgel for Effective Management of Dermatophytosis.

Dermatophytosis, the most prevalent fungal infection, is witnessing a rising incidence annually. To address this challenge, we developed a terbinafine-loaded oil-in-water nanoemulsion (TH-NE) through the aqueous microtitration method. The formulation comprised olive oil (oil phase), Span 80 (surfactant), and propylene glycol (co-surfactant). Pseudo-phase ternary diagrams and thermodynamic studies underscored the stability of TH-NE. Employing the Box-Behnken design (BBD), we optimized TH-NE, which resulted in a remarkable particle size of 28.07 nm ± 0.5, a low polydispersity index (PDI) of 0.1922 ± 0.1, and a substantial negative zeta potential of -41.87 mV ± 1. Subsequently, TH-NE was integrated into a 1.5% carbopol matrix, yielding a nanoemulgel (TH-NEG). Texture analysis of TH-NEG demonstrated a firmness of 168.00 g, a consistency of 229.81 g/s, negative cohesiveness (-83.36 g), and a work of cohesion at -107.02 g/s. In vitro drug release studies revealed an initial burst effect followed by sustained release, with TH-NEG achieving an impressive 88% release over 48 h, outperforming TH-NE (74%) and the marketed formulation (66%). Ex vivo release studies mirrored these results, with TH-NEG (86%) and TH-NE (71%) showcasing sustained drug release in comparison to the marketed formulation (67%). Confocal microscopy illustrated that TH-NEG and TH-NE penetrated to depths of 30 µm and 25 µm, respectively, into the epidermal layer. Furthermore, dermatokinetic studies highlighted the enhanced drug penetration of TH-NEG compared to TH-NE through mouse skin. In summary, our study establishes TH-NEG as a promising carrier for terbinafine in treating dermatophytosis, offering improved drug delivery and sustained release potential.

Exploration of a W/O Nanoemulsion for Antibiofilm Activity against Cariogenic Enterococcus faecalis.

A ciprofloxacin-loaded water-in-oil nanoemulsion (CPX-NE) was prepared and evaluated for the antimicrobial effect against oral biofilms produced by Enterococcus faecalis. CPX-NE was prepared by ultrasonication using functional excipients oleic acid (oil phase), Span 80 (surfactant), and Transcutol P (cosurfactant). Rheological parameters (viscosity = 20 ± 1.24 cp) confirmed optimum values for CPX-NE, a pH of 6.5 ± 0.23 suggested the simulation of CPX-NE with the pH of the mouth cavity, refractive index (1.46 ± 0.22), and % transmittance (92.34 ± 0.02) indicated the isotropic nature of the NE. The droplet size (72.19 ± 1.68 nm), polydispersity index (0.142 ± 0.02), and ζ potential (-28 mV) demonstrated a narrow size distribution and electrostatically stabilized NE. The morphology of the optimized formulation showed uniform spherical nanodroplets, as seen in fluorescence microscopy. In vitro drug release showed an initial burst effect followed by sustained release for 48 h, following Fick's diffusion. The minimum biofilm inhibitory and eradication concentration (MBIC/MBEC) was determined to compare CPX-NE with ciprofloxacin plain drug solution (CPX-PS) for their efficacy. CPX-NE demonstrated a significant inhibitory and eradication effect compared to CPX-PS. It was concluded that the developed CPX-NE has effective antibiofilm activity against E. faecalis and may be useful in the prevention and treatment of dental caries.

Needle Fear among Children during Mass Measles Rubella (MR) Injectable Vaccination Campaign in North India: an Observational Study.

The cross-sectional observational study evaluated the prevalence and predictors of needle-fear among school-going children during mass Measles-Rubella (MR) immunization campaign (year 2017) in the north Indian city of Chandigarh. Fear of needle was assessed using a single-item self-report global question, anxiety was assessed using the Likert scale (score 1-5) and the standardized "Children Faces Scale" where facial responses were graded from 0 to 4. Out of a total sample of 2568 school children, 1225 (47.7%) reported needle fear (95% CI: 45.8%-49.6%) on a global single item assessment. On an anxiety related Likert scale, 52.3% did not respond (mainly younger children) and among those who responded, 42.6% (523/1226) showed significant anxiety (score of ≥3 on Likert scale of 1 to 5). Finally, 17.4% children (95% CI: 15.9%-18.9%) (n = 446/2568) scored 2 or above (indicating significant needle fear) on the 'Children Faces Scale' during the actual vaccination procedure. The needle fear were significantly increased among girl students as compared to boys (adjusted OR 2.58; 95% CI: 2.05-3.24, p < 0.001) as well as children accompanied by their parents (adjusted OR 2.05; 95% CI:1.57-2.69, p < 0.001). On the other hand, needle fear was significantly lowered in children studying in private schools as compared to public school children (adjusted OR 0.45; 95% CI: 0.28-0.74, p = 0.002). The needle fear, which was an overriding concern in the minds of girls, children accompanied by their parents, and public-school students, must be proactively addressed for successful mass vaccination campaigns. These findings assume further importance with recent international roll out of COVID 19 vaccine.

Remote Monitoring and Holistic Care of Home-Isolated COVID-19 Positive Healthcare Workers Through Digital Technology During the Omicron (B1.1.529) Wave: A Prospective Cohort Study From India.

Background: Remote monitoring through digital technology offers a promising solution for the diverse medical, psychological and social issues that plague patients with COVID-19 under home-isolation, but remain neglected due to a lack of streamlined medical services for these patients. Methods: This prospective cohort study determined the feasibility of remote telemonitoring of healthcare workers with mild COVID-19 under home isolation during the Omicron (B1.1.529) wave and characterized their clinico-demographic profile. A holistic monitoring model comprising of mandatory phone calls at the beginning and end of isolation, assisted by home oximetry, predesigned google forms, and opt-in software-based (eSanjeevani OPD) teleconsultation was employed. Factors associated with development of symptomatic disease were also determined. Results: Out of 100 COVID-19 positive healthcare workers under home-isolation, data for 94 participants was available [median age 27(20-52) years, 56(60%) females]. 93(99%) patients were previously vaccinated for COVID-19 (median time from last dose = 248 days); 34(36%) had a past history of COVID-19. Fever (67%), myalgia (69%), sore throat/dry cough (70%), and running nose (45%) were the most common symptoms. No patient progressed to moderate-severe disease or required care escalation during the remote monitoring period. Most participants reported several additional psychosocial concerns which were adequately addressed. Symptomatic patients had higher BMI (24.1 vs. 21.8kg/m2, p = 0.01) compared to asymptomatic patients. Age, past infection with COVID-19, and time since last vaccine dose were not different between symptomatic and asymptomatic patients. Conclusion: COVID-19 patients under home isolation have multi-faceted medical and psychosocial issues which can be holistically managed remotely through digital technology.

Structure of a 14-3-3ε:FOXO3apS253 Phosphopeptide Complex Reveals 14-3-3 Isoform-Specific Binding of Forkhead Box Class O Transcription Factor (FOXO) Phosphoproteins.

The transcriptional activity of Forkhead Box O3 (FOXO3a) is inactivated by AKT-mediated phosphorylation on Serine 253 (S253), which enables FOXO3a binding to 14-3-3. Phosphorylated FOXO3a binding to 14-3-3 facilitates the nuclear exclusion of FOXO3a, causing cancer cell proliferation. The FOXO3a/14-3-3 interaction has, therefore, emerged as an important therapeutic target. Here, we report a comprehensive analysis using fluorescence polarization, isothermal titration calorimetry, small-angle X-ray scattering, X-ray crystallography, and molecular dynamics simulations to gain molecular-level insights into the interaction of FOXO3apS253 phosphopeptide with 14-3-3ε. A high-resolution structure of the fluorophore-labeled FOXO3apS253:14-3-3ε complex revealed a distinct mode of interaction compared to other 14-3-3 phosphopeptide complexes. FOXO3apS253 phosphopeptide showed significant structural difference in the positions of the -3 and -4 Arg residues relative to pSer, compared to that of a similar phosphopeptide, FOXO1pS256 bound to 14-3-3σ. Moreover, molecular dynamics studies show that the significant structural changes and molecular interactions noticed in the crystal structure of FOXO3apS253:14-3-3ε are preserved over the course of the simulation. Thus, this study reveals structural differences between the binding to 14-3-3 isoforms of FOXO1pS256 versus FOXO3apS253, providing a framework for the rational design of isoform-specific FOXO/14-3-3 protein-protein interaction inhibitors for therapy.