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Abstract Current influenza vaccines are strain-specific and require frequent updates to combat new strains, making a broadly protective influenza vaccine (BPIV) highly desirable. A promising strategy is to induce T-cell responses against internal proteins conserved across influenza strains. In this study, pH1N1 pre-exposed pigs were immunized by aerosol using viral vectored vaccines (ChAdOx2 and MVA) expressing matrix (M1) and nucleoprotein (NP). Following H3N2 challenge, all immunizations (M1, NP or NPM1) reduced lung pathology, but M1 alone offered the greatest protection. NP or NPM1 immunization induced both T-cell and antibody responses. M1 immunization generated no detectable antibodies but elicited M1-specific T-cell responses, suggesting T cell-mediated protection. Additionally, a single aerosol immunization with the ChAdOx vaccine encoding M1, NP and neuraminidase reduced lung pathology. These findings provide insights into BPIV development using a relevant large natural host, the pig.

Abstract Hypertension poses a critical threat to health in India, being the predominant risk factor for mortality and disability. With over 70% of outpatient care being provided by the private sector, our study investigated the practices and incentives of private health providers in screening, diagnosing, treating, monitoring, and counseling hypertension patients in rural and peri-urban India. Conducted from April 2020 to February 2021, the qualitative study involved 46 participants, including various healthcare professionals and patients in three Telangana state districts. Analysis revealed a lack of recognition of hypertension’s gravity among private providers in these areas, leading to inconsistent screening practices and varied diagnostic thresholds, particularly among rural medical practitioners. Both formal and informal providers lacked standardized protocols and follow-up mechanisms, with limited technical knowledge about hypertension observed, especially among rural practitioners who were often the first point of contact. Drug effectiveness, and incentives from pharmaceutical sales representatives influenced prescribing practices. Diagnostic labs also offered financial incentives for patient referrals. Thus, aligning providers’ objectives with patient preferences and public health goals is crucial. To encourage evidence-based hypertension care, the government and NGOs could implement strategies such as tailored incentives, financial rewards, tax benefits, accreditation, and recognition for private healthcare providers. Professional bodies in the private sector should establish programs emphasizing quality assurance and certifications. Future research should focus on designing and testing new models for private sector hypertension service delivery, coupled with targeted interventions to enhance care in rural and peri-urban settings.

Hepatitis C virus infection is one of the main causes of liver disease that can lead to liver cirrhosis and finally to the chronic development of Hepatocellular Carcinoma (HCC). With 8 different HCV genotypes circulating, it becomes necessary to characterize the pathogenesis caused by each one of the HCV genotypes infecting population of a particular setting. Present study aims to identify the circulating Hepatitis C virus (HCV) genotypes in the different areas of State of Uttar Pradesh, India and understand their clinical etiology and related co-morbidities. The patients reporting to Sharda Hospital, Uttar Pradesh, India who were diagnosed positive for HCV were included in the study. The informed consent was obtained and then blood was drawn. In-house primers, for all the 8 genotypes were prepared and RT-PCR was performed. The amplified product was subjected to Agarose gel electrophoresis to identify the genotypes present in individual samples. Total 30 serum samples were taken. Of these, 21 (70%) showed presence of multiple genotypes, while 7 (23.33%) showed positivity for single genotype and two did not show any bands. Presence of multiple genotypes in individual patient has been reported for the first time. The pathological consequences of multiple genotypes within one host need to be studied further in terms of increased risk of developing a chronic liver disease. Further studies are being undertaken to study association of specific HCV genotype and multiple genotypes, Core, NS3 and NS5 viral proteins with the disease progression to develop predictors of liver cirrhosis and HCC.

Assessing the pharmacokinetics of monoclonal antibodies (mAbs) in relevant animal models is essential for designing improved formulations and developing mAb delivery platforms. We have established the pig, a large natural host animal for influenza with many similarities to humans, as a robust model for testing the therapeutic efficacy of anti-influenza mAbs and evaluating mAb delivery platforms. Here, we compared the pharmacokinetic characteristics of two anti-influenza hemagglutinin mAbs, human 2-12C and porcine pb27, in Göttingen minipigs and Landrace × Large White outbred pigs. Minipigs offer the advantage of a more stable weight, whereas outbred pigs are more readily available but exhibit rapid growth. Outbred pigs and minipigs showed similar pharmacokinetics and a similar porcine pb27 half-life (half-life of 15.7 days for outbred pigs and 16.6 days for minipigs). In contrast, the half-life of human 2-12C was more rapid in two of the minipigs but not in the outbred pigs, correlating with the development of antidrug antibodies in the two minipigs. Our results demonstrate that both outbred pigs and minipigs are appropriate models for pharmacokinetic studies and the evaluation of mAb delivery platforms, potentially bridging the gap between small animals and human trials.

Objective: The severe acute type of respiratory distress caused by Coronavirus disease 2019 (COVID-19) was responsible for the global pandemic of 2019. While most of the focus of vaccine/drug molecules is on the receptor, there are certain enzymes that also need to be checked. Cell surface proteases are one of these. Activation of the virus spike protein becomes more complicated when many host proteases are involved. As many Variants of Concerns have been reported in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), this study aimed to understand the proteolytic function of Furin in each, and its involvement in virus-host interaction. Material and Methods: Spike Protein sequence alignment, furin cleavage site prediction of variants: Wuhan, Alpha (B.1.1.7), Beta (B.1.351), Gamma (P.1), Delta (B.1.617.2) and Omicron (B.1.1.529), and protein-protein docking studies have been undertaken using appropriate bioinformatics tools. Results: It was observed that when compared to previous variations, the November 2021, outbreak of Omicron variant showed 50 amino acid substitutions in the Spike protein. Thus, in addition to the Angiotensin Converting Enzyme 2 (ACE-2) receptor, the role of virus binding sites to act as “Addition Receptors” for viral entry has been reported here. Conclusion: It was observed that substitution of basic amino acids in the Omicron variant may be responsible for the recognition of furin cleavage sites and the presence of furin cleavage site in the receptor binding domain (RBD) region will thus enhance viral transmission. If these sites are utilized in formulation of new drugs/vaccine molecules to target the furin hydrolyse sites, we may be able to add to the existing course of COVID-19 treatment.

Background: The burden of foodborne diseases and antimicrobial resistance carried by key foodborne pathogens in India is unknown due to a lack of an integrated surveillance system at the human-animal interface. Methods: We present data from the WHO-AGISAR (Advisory Group on Integrated Surveillance of Antimicrobial Resistance), India project. Concurrent human and animal sampling was done across a large area across north India. Community-acquired diarrhea cases (n = 1968) of all age groups were included. Cross-sectional sampling of stool/ intestinal contents (n = 487) and meat samples (n = 419) from food-producing animals was done at farms, retail shops, and slaughterhouses. Pathogens were cultured and identified, and antimicrobial susceptibility was performed. Results: Over 80% of diarrhoeal samples were obtained from moderate to severe diarrhea patients, which yielded EAEC (5%), ETEC (4.84%), EPEC (4.32%), and Campylobacter spp. (2%). A high carriage of EPEC (32.11%) and Campylobacter spp. (24.72%) was noted in food animals, but the prevalence of ETEC (2%) and EAEC (1%) was low. Atypical EPEC (aEPEC, 84.52%, p ≤0.0001) were predominant and caused milder diarrhea. All EPEC from animal/poultry were aEPEC. Overall, a very high level of resistance was observed, and the MDR rate ranged from 29.2% in Campylobacter spp., 53.6% in EPEC, and 59.8% in ETEC. Resistance to piperacillin-tazobactam, cefepime, ceftriaxone, and co-trimoxazole was significantly higher in human strains. In contrast, resistance to ciprofloxacin, aminoglycosides, and tetracycline was higher in animal strains, reflecting the corresponding usage in human and animal sectors. ESBL production was commoner in animal isolates than in humans, indicating high use of third-generation cephalosporins in the animal sector. C. hyointestinalis is an emerging zoonotic pathogen, first time reported from India. Conclusion: In one of the most extensive studies from India, a high burden of key foodborne pathogens with MDR and ESBL phenotypes was found in livestock, poultry, and retail meat.

The emergence of SARS-CoV-2 created a havoc worldwide, causing high morbidity, serious complications and mortality. The ORF1ab of SARS-CoV-2 has 16 non-structural proteins which are required for genome replication and transcription. All of these are druggable targets, of which NSP12 (RNA-dependent RNA polymerase), was selected as a potential target for drug molecules. Remdesivir is a recommended drug for SARS-CoV-2 and it targets the RdRp protein. Although Remdesivir was given to COVID-19 patients based on their clinical manifestations, yet the transmission and spread of the virus continued and to add to its pandemicity, new variants emerged from time to time. This necessitates the need for molecular modification of existing antiviral drugs so that more precise targets for halting viral replication can be selected. For this, the approach used was repurposing of the existing drugs. In the present study, ten FDA-approved drugs were chosen on the basis of their properties of inhibiting the RdRp protein. These drugs were subjected for checking the docking score with the target protein. Of these, Remdesivir, Ribavirin, Favipiravir and Baloxavir were taken for further analysis on the basis of their best scores. These drugs were then modified to check the efficiency to inhibit the RdRp and to stop the replication rate of the virus. We docked the modified drugs with the macrodomain of RdRp by using the CB-Dock web server and checked the binding affinity and amino acid contact residues. The modified drugs were also checked for bioactivity in the Molinspiration cheminformatics online tool. Our results showed increased affinity for RdRp of SARS-CoV-2 when compared to the original compound. We also checked the synthetic accessibility of the drugs using the SwissADME tool. The study showed promising results when modified. The findings reported need further confirmation through wet lab studies.

Abstract HIV affects more than 38 million people worldwide. Although HIV can be effectively treated by lifelong combination antiretroviral therapy, only a handful of patients have been cured. Therapeutic vaccines that induce robust de novo immune responses targeting HIV proteins and latent reservoirs will likely be integral for functional HIV cure. Our study shows that immunization of naïve rhesus macaques with arenavirus-derived vaccine vectors encoding simian immunodeficiency virus (SIVSME543 Gag, Env, and Pol) immunogens is safe, immunogenic, and efficacious. Immunization induced robust SIV-specific CD8+ and CD4+ T-cell responses with expanded cellular breadth, polyfunctionality, and Env-binding antibodies with antibody-dependent cellular cytotoxicity. Vaccinated animals had significant reductions in median SIV viral load (1.45-log10 copies/mL) after SIVMAC251 challenge compared with placebo. Peak viral control correlated with the breadth of Gag-specific T cells and tier 1 neutralizing antibodies. These results support clinical investigation of arenavirus-based vectors as a central component of therapeutic vaccination for HIV cure.

In India and other affected countries, Omicron variant of SARS-CoV-2 has shown faster transmission but less clinical severities when compared to Delta strain. Present study was aimed to investigate how molecular changes in the spike proteins of Omicron variant has increased its transmission but reduced the disease severity. We report molecular interactions of Spike proteins of Delta and Omicron variants with ACE-2 receptor to explain how change in chemical and physical nature of mutated amino acids of Omicron variant has affected the internalization competence of virus into host cell. The Research Collaboratory Structural Bioinformatics (RCSB) and Protein Data Bank (PDB) were used to construct ACE2-Spike Protein interaction. The binding affinity of both omicron and delta variant spike proteins with human ACE2 receptor was observed. Spike protein of Omicron variants has revealed total number of 93 dissimilarities of amino acids from Delta strain,15 of which are in its Receptor Binding Domain (RBD). Our study showed that RBD of Delta variant contained only one hydrophobic amino acid whereas there were 6 hydrophobic amino acids in the RBD of Omicron variant. We report that increased number of Hydrophobic Amino Acids in RBD of Omicron variant affects its binding with ACE2 receptor to enter into the cell. The failure of internalization of virus has increased concentration of extracellular virions at nasopharyngeal region leading to faster expulsion of infective droplets during coughing or sneezing to increase transmission but has reduced the severity of infection. The reported observations could prove to be of public health and therapeutic significance.

Arenavirus-based vectors are being investigated as therapeutic vaccine candidates with the potential to elicit robust CD8 T-cell responses. We compared the immunogenicity of replicating (artPICV and artLCMV) and non-replicating (rPICV and rLCMV) arenavirus-based vectors expressing simian immunodeficiency virus (SIV) Gag and Envelope (Env) immunogens in treatment-naïve non-human primates. Heterologous regimens with non-replicating and replicating vectors elicited more robust SIV IFN-γ responses than a homologous regimen, and replicating vectors elicited significantly higher cellular immunogenicity than non-replicating vectors. The heterologous regimen elicited high anti-Env antibody titers when administered intravenously, with replicating vectors inducing significantly higher titers than non-replicating vectors. Intramuscular immunization resulted in more durable antibody responses than intravenous immunization for both vector platforms, with no difference between the replicating and non-replicating vectors. Overall, both replicating and non-replicating arenavirus vectors generated robust T- and B-cell-mediated immunity to SIV antigens in treatment-naïve non-human primates, supporting further evaluation of these vectors in a clinical setting for HIV therapy.

Anaerobic bacteria are part of the normal human skin flora. However, anaerobic infections could have different clinical courses with outcomes ranging from local abscesses to life-threatening conditions. Any long-term wound infection or a wound discharging pus with a foul smell is an indication of anaerobic infections. We present here a series of three cases of infection in patients injured in road traffic accidents (RTA) in which Anaerococcus prevotii was identified as the pathogen. Samples isolated from tissues of patients from three different RTAs were received in anaerobic conditions in Robertson Cooked Meat medium (RCM) within 2-4 h of collection. RCM was incubated for 24 h and then inoculated on three blood agars (BA) plates cultured anaerobically in a Gas Pack Jar, in a CO 2 incubator, or aerobically. No growth was noted on the aerobically incubated plate. After 48 h, anaerobic plates were examined for growth and a Gram stain was performed. The identity of isolated colonies was confirmed by VITEK-2, and sensitivity testing was done by the pour plate method using Epsilon meter strips. All three tissue samples isolated from (1) the right leg, (2) the right inguinal region, and (3) the left thigh of patients revealed Anaerococcus prevotii , and two isolates showed resistance to the antibiotic metronidazole. Any injury with long-term infection, especially in patients suffered from RTAs, needs to be scrutinized for anaerobic infections since they are common in RTA related injuries. No random medication should be administered without prior culture sensitivity testing, because it might contribute to metronidazole or other antibiotics resistance.

Leprosy is a disease with spectral clinical manifestations along with two types of reactions, type 1 reaction (T1R) and type 2 reaction (T2R). T1R especially occurs because of the defensive upgradation of cell-mediated immunity (CMI) to M. leprae antigens. T1R is the main cause of disability in leprosy. The role of conventional adaptive T cells has been well studied to understand T1R. A comprehensive understanding of the role of unconventional T cells in the manifestation of inflammation during T1R is crucial and has not been studied. In our study, we found significantly higher plasma levels of TNFα, IL1β, IL17, and IP10 in T1R when compared to non-reaction (NR). Gene expression for cytokines in blood circulation by qPCR showed significantly higher expression of IFNγ, IP10, TNFα, IL6, IL17A and chemokines CCL3, CCR1, CCR5, and CXCR3 in T1R as compared to NR. Frequencies of NKT-like cells (48.7 %) and NK cells (22.3 %) were found significantly higher in T1R in comparison to NR (36.9 %, 18.3 %, respectively) (p = 0.0001). Significantly lower levels of γδT cells (3.32 %) were observed in T1R in comparison to NR (5.16 %). The present study has provided evidence for the first time on the role of plausible unconventional T cells in the immunopathogenesis of T1R in leprosy.

Introduction In the ongoing severe acute respiratory syndrome coronavirus 2 pandemic, a long hospital stay and empirical broad-spectrum antibiotics make the patients prone to acquire nosocomial infections especially with unconventional organisms, and Chryseobacterium gleum is one such rare nosocomial pathogen.

Urinary tract infections (UTIs) are the leading cause of outpatient visits and nosocomial infections worldwide resulting in increased healthcare costs. Information about the disease-associated pathogens and their susceptibility profile is of paramount importance for choosing antimicrobials and containing the alarming rise in microorganisms’ drug resistance. This study aimed to investigate the prevalence of gram-negative and gram-positive uropathogens in hospitalized adult patients, considering their sensitivity profile. The study retrospectively analyzed 2099 urine samples received from December 2019 to May 2020. The isolates were identified by standard microbiological methods, and sensitivity testing was done following the Clinical and Laboratory Standards Institute (CLSI) guidelines (2019). Out of the 2099 samples tested, 212 were positive. The vast majority of samples (97.6%) was received from women. Escherichia coli (34.9%) was the most common gram-negative pathogen, while Enterococcus spp. (15.1%) prevailed among gram-positive organisms. Among gram-negative organisms, a high susceptibility was observed for aminoglycosides (amikacin, netilmicin), nitrofurantoin, and carbapenems, while a high resistance was found towards co-trimoxazole, fluoroquinolones, and cephalosporins. We confirmed that nitrofurantoin, a traditional oral drug, still demonstrates good activity against uropathogens. Thus, there is an urgent need to study uropathogens and their susceptibility patterns to control the inadvertent use of antimicrobials and the spread of multidrug-resistant strains.

Actinomycosis is an indolent, slowly progressive infection caused by Gram-positive facultative anaerobic bacteria from the genus Actinomyces . These bacteria have been reported as a cause of ophthalmic infections such as endophthalmitis, keratitis, and canaliculitis. The objective of the present study was to investigate the pattern and antibiotic sensitivity profile of anaerobes isolated from lesions in the medial canthus of the eye. Three pus aspirate samples (from eye) were delivered to a microbiology laboratory in a strict anaerobic condition in Robertson Cooked Meat media (RCM). The samples were inoculated on Blood Agar and incubated anaerobically in a Gas Pack Jar incubator at 5%-10% CO 2 and in aerobic condition at 37°C. Pure colonies isolated on anaerobically incubated plates were identified by the VITEK® 2 COMPACT system. Antibiotic sensitivity testing was conducted using an Epsilometer-strip test. Three isolates identified and confirmed with the help of VITEK® 2 were Actinomyces israelii , Actinomyces odontolyticus, and Actinomyces meyeri . All three species of Actinomyces were sensitive to Vancomycin, Moxifloxacin, and Imipenem, but they were resistant to Metronidazole. Since there have been several cases of anaerobic ophthalmic infections reported to date, samples from patients with chronic eye infections should be analyzed for anaerobic culture for correct diagnosis and proper treatment. Moxifloxacin but not Metronidazole is a suitable drug for the treatment of anaerobic eye infection.

Background Human papillomavirus (HPV) E6/E7 mRNA tests determine the oncogenic activity of the virus and represent a good clinical biomarker for predicting the risk of cervical cancer. So, the present study was conducted to know the role of HPV E6/E7 mRNA as a predictive biomarker for cervical carcinoma. Methodology The present study was conducted on 55 clinical samples of cervical scrapings and biopsy from the clinically suspected cases (based on signs and symptoms) of cervical cancer having abnormal PAP smear. The samples were processed in three steps—(1) HPV DNA detection, (2) HPV E6/E7 mRNA detection, and (3) histopathological analysis. Results Out of a total of 55 patients, 16 (29.09%) were positive for both HPV E6/E7 mRNA and HPV DNA and six were positive for only HPV DNA. So, a total of 22 (40%) patients were positive for HPV DNA. Out of these 22 samples, 10 (45.5%) were of HPV-16, six (27.3%) were of HPV-18, four (18.2%) were of HPV-31, and two (9.1%) were of HPV-45. Out of total 16 patients positive for HPV E6/E7 mRNA, 10 (62.5%) were of genotype 16 and six (37.5%) were of genotype 18. The patients who were found positive for HPV 31 and 45 genotypes did not have E6/E7 mRNA expression. On colposcopic-guided biopsy, among these 16 samples, eight (50%) were diagnosed with invasive squamous cell carcinoma, six (37.5%) with cervical intraepithelial neoplasia grade 3 (CIN3), and two (12.5%) with CIN2. Out of those six patients in whom only HPV DNA was positive, five had normal biopsy findings and one had CIN1. Conclusion The present study suggests that HPV E6/E7 mRNA detection could be more reliable than DNA testing for predicting the risk of progression of HPV-induced cervical lesions to cervical carcinoma and it can be used as a non-invasive tool for triage and patient follow-up.

Introduction Low-frequency noise (LFN) is hazardous to hearing. Long-term exposure to LFN may lead to vibroacoustic disease (VAD), which not only affects a specific organ but the physiological function of entire systems, such as the auditory, phonatory, respiratory, and cardiac systems. Moreover, VAD may lead to many psychological problems and hence affect the quality of life.

Echinococcosis or hydatid disease is caused by the larval stage of the dog tapeworm, that is, Echinococcus granulosus, E. multilocularis, E. vogeli, or E. oligarthrus. Echinococcus granulosus causes cystic echinococcosis, which has a worldwide distribution. Liver is the most common site, affecting approximately two-third of the patients, whereas lung involvement is seen in approximately 25% of cases. This case is a very rare scenario of bilateral pulmonary hydatid cysts in a young child having exposure to a pet dog with negative hydatid serology and normal eosinophil count.

Purpose: To report clinical features, antibiotic susceptibility profile, management, and outcomes of a cluster outbreak of post-cataract surgery Pseudomonas stutzeri endophthalmitis. Methods: This was a hospital-based case series in which 14 patients with acute postoperative endophthalmitis who underwent cataract surgery on the same day were included. Based on severity of presentation, they either underwent pars plana vitrectomy (PPV) with intraocular antibiotics (IOAB) or vitreous tap with IOAB. Vitreous aspirates and environmental surveillance samples were inoculated on culture media and further processed by MALDI-TOF MS for identification and Vitek3 for susceptibility profile. Results: There were 8 females and 6 males with a mean age of 62.14 ± 8.08 years. Presenting signs included corneal folds (100%), hypopyon (57.1%) and fibrin (50%). Ten patients with mild presentation underwent vitreous tap with IOAB. Four patients with severe presentation underwent PPV with IOAB. Pseudomonas stutzeri was isolated from the vitreous samples and was pan-sensitive. Six eyes required multiple interventions. Favorable outcome was obtained in 12 eyes, one eye developed phthisis, and one patient was lost to follow-up. Conclusion: We report the first ever cluster outbreak of Pseudomonas stutzeri endophthalmitis following phacoemulsification with IOL implantation in a single surgeon setting. Majority of the patients had a mild presentation and responded well to targeted anti-microbial treatment.

Background: More and more cases of myelin oligodendrocyte glycoprotein (MOG) antibody are being diagnosed with the availability of laboratory tests helping us to know the differing patterns from AQP-4 antibody disease and we need to understand the natural course, treatment, and prognosis in a better way. Objectives: Neuromyelitis optica spectrum disorder (NMOSD) and anti-MOG syndromes are immune-mediated inflammatory demyelinating conditions of the central nervous system (CNS) that mainly involve the optic nerves and the spinal cord. We conducted this study to compare demographic, clinical, laboratory, and radiological features of AQP-4 antibody and MOG antibody positive patients. Methods: A single-centre retrospective observational study from a large tertiary care university centre of Northwest India conducted during 2019--2021. We screened all patients presenting with acute CNS demyelinating attacks and recruited total 47 patients of which 25 were positive for AQP4 antibody and 22 were positive for MOG antibody. No patient tested positive for both antibodies. Data were collected using a standardized format including demographic, clinical, laboratory, and neuroimaging data. Results: In our study, total 47 patients were included, amongst which 25 patients were AQP4 antibody and 22 patients were MOG antibody positive. Though there was no gender preponderance, pediatric patients were more frequently affected in MOG antibody positive group. In AQP-4 antibody positive patients, myelitis was most common presenting clinical feature followed by optic neuritis (ON), simultaneous ON with myelitis, and brainstem syndrome. In MOG antibody positive group, myelitis was the commonest phenotype followed by ON, brainstem syndrome, and cerebral syndrome. The neuroimaging revealed involvement of medulla mainly area postrema, cervicodorsal spinal cord and extension of cervical lesion up to brainstem more commonly in AQP4 antibody group, on the other hand involvement of upper brainstem (midbrain and pons), cortex, and conus was more common in MOG antibody group. Conclusion: We have made an attempt to find differentiating features in AQP-4 vs. MOG antibody positive cases but they were of no statistically significance value as the numbers were small. Further larger studies may prove helpful in planning better strategies in two groups.

IntroductionT cells are crucial for pathogenesis as well as control for tuberculosis (TB). Although much is known about the signaling pathways which are required for the activation of T cells during acute infection but the way these cells respond during persistent of infection still remained elusive. Therefore, it is rationale to understand T cell activation during tuberculous pleural effusion (TPE), which is similar to bacterial persistency system.MethodsHerein, we will employ T cell receptor (TCR) based approaches for studying events of T cell activation pathways in cells of blood and pleural fluid among patients with TPE. We performed spectrofluorimetric analysis to study effect of M. tuberculosis antigens, ESAT-6 and Ag85A stimulation on intracellular calcium levels, Phosphorylation levels of ZAP-70 (Zeta-chain-associated protein kinase 70), PKC-θ (Protein kinase C theta), Erk1/2 (Extracellular signal-regulated kinase 1 and 2) and p-38 two important members of MAPKs (Mitogen activated Protein kinases) in CD3 and CD28 induced cells of blood and pleural fluid of same patients with TPE by western blotting. Patients with non-TPE were also included as matching disease controls in this study.ResultsWe observed significantly higher intracellular calcium levels, Phosphorylation levels of ZAP-70, Erk1/2 and p-38 in CD3 and CD28 induced cells of pleural fluid as compared to the blood cells of same patients with TPE. Alteration in the activation of these events has also been noted after stimulation of ESAT-6 and Ag85A.DiscussionPresent study demonstrated up-regulated activation of TCR mediated T cell signaling events at local disease site (Pleural fluid) as compared to the blood sample of TB pleurisy patients which could be involved in T-cell dysfunctioning during the progression of the disease and also could be responsible for Th 1 dominance at local disease site in patients with TPE.

Introduction: This study assessed the relationship between intention to receive a COVID-19 vaccine and intention to receive a seasonal influenza vaccine, as well as how intention to receive a COVID-19 vaccine has changed during the pandemic. Methods: Residents of British Columbia aged 25–69 years were invited to complete an online cross-sectional survey from August 2020 - March 2021. Mixed-effects logistic regression models assessed the relationship between intention to receive a COVID-19 vaccine and intention to receive the seasonal influenza vaccine. A generalized additive mixed model was used to investigate changes in COVID-19 vaccine intention during the pandemic (August 2020–March 2021). The relationship between intention to receive a COVID-19 vaccine and retrospective overall perceived value of vaccines prior to and during the pandemic was also considered. Results: Of 6,333 participants, 80.2 % of participants were ‘somewhat or very likely’ to receive a COVID-19 vaccine and 69 % of participants reported intending to receive a seasonal influenza vaccine. In multivariable modeling, intention to receive a COVID-19 vaccine was strongly associated with intention to receive a seasonal influenza vaccine (aOR = 4.25, 95 %CI 3.33–5.43). Intention to receive a COVID-19 vaccine increased over the study period (p

Abstract Despite the availability of effective medication, blood pressure control rates are low, particularly in low‐ and middle‐income countries. Adherence to medication and follow‐up visits are important factors in blood pressure control. This study assessed the effectiveness of reminder telephone calls on follow‐up visits and blood pressure control among hypertensive patients as part of the Mumbai Hypertension Project. This project was initiated by PATH with the support from Resolve to Save Lives from January 2019 to February 2020. The study included hypertensive patients attending 164 private practices in Mumbai, India; practitioners screened all adults visiting their clinic during the project period. Among 13 184 hypertensive patients registered, the mean age was 53 years (SD = 12.38) and 52% were female. Among the 11 544 patients that provided phone numbers and gave consent for follow‐up calls, 9528 responded to phone calls at least once and 5250 patients followed up at least once. Of the 5250 patients, 82% visited the clinic for follow‐up visit within one month after receiving the phone call. The blood pressure control rate among those who answered phone calls and who did not answer phone calls increased from 23.6% to 48.8% (P

Abstract More than half of patients with hypertension require two or more medicines to control blood pressure. Combinations of anti‐hypertensive medicines are available as Single Pill Combinations (SPCs) or Single Agent Pills (SAPs). SPCs of two or more anti‐hypertensive medicines facilitate simpler dosing schedules, decrease pill burden, increase adherence to medicine, and simplify procurement and distribution. Despite this, equivalent combinations of separate pills (SAPs) are often prescribed instead of SPCs under the assumption that SAPs are priced lower. This study compared prices of anti‐hypertensive SPCs and equivalent SAPs in the private health care sector of India. High sales volume anti‐hypertensive SPCs and SAPs were selected from 2018 private sector pharmaceutical sales data. SPCs and SAPs price information was collected from online pharmacy websites between November 2019 and January 2020. Anti‐hypertensive SPCs represent approximately 39.1% of India's private sector anti‐hypertensive drug market. Multiple manufacturers produce the same top‐selling SPCs, suggesting a viable and competitive market. A comparison of SPCs and SAPs across different manufacturers showed that the lowest prices of both SPCs and the sum of component SAPs were nearly identical across different manufacturers. An analysis of dual‐drug SPCs and SAPs by the same manufacturer showed that most manufacturers (five of six) had priced their SPCs higher than SAPs. These observations suggest that the price of SPCs could be lowered to match the combined price of the component SAPs, and manufacturing costs and market forces do not present a barrier to the implementation of anti‐hypertensive SPCs.

Transthyretin amyloid cardiomyopathy (ATTR-CM) is potentially a fatal disease characterized by abnormal buildup of amyloid fibrils primarily in the heart causing progressive heart failure. It is categorized into two subtypes-hereditary ATTR and wild type ATTR. Previously, no treatment is available, due to which liver transplantation, multi-organ transplantation, and symptomatic treatment were the only therapies at that time. Approval of Vyndaqel (tafamidis meglumine) and Vyndamax (tafamidis) capsules in 2019, acts like a kick in the research fields due to which other therapeutics are now emerging. Several clinical trials are going on to evaluate the efficacy of different drugs in ATTR-CM. Most of the clinical trials demonstrated positive outcomes which leads to further evaluation for confirmation. In this review treatment pipeline, ongoing clinical trials and challenges related to ATTR-CM are described.

Nocardia africana is a recently identified organism and has rarely been reported to cause mycetoma. Here we report the case of a 40-year-old woman who presented with discharging sinuses and nodules for the past 7 years along with few discrete axillary lymph nodes. Cultures and Maldi-TOF MS (Matrix-assisted laser desorption/ionization–time of flight mass spectrometry) method identified the causative organism as Nocardia africana/nova. The organism was acid-fast positive on modified Ziehl-Neelsen stain and Gram's stain revealed branched filamentous beaded gram-positive bacilli, while histopathology showed granulation tissue along with few ill-defined epithelioid cell granulomas, with giant cells. Based on the sensitivity report, the patient was started on tablet moxifloxacin and cotrimoxazole, and has shown considerable improvement at 2.5 months of follow-up.

Non fermenting gram-negative bacilli (NFGNB) are recently striving as uropathogens. The present study was conducted to isolate the common species of bacteria in NFGNB causing urinary tract infection (UTI) and its correlation with comorbid conditions and to study the antibacterial susceptibility pattern. This retrospective study was done at the diagnostic Microbiology laboratory of a tertiary care hospital. Urine samples were collected for the period of six months. These samples were plated on blood agar and MacConkey agar and incubated at 37°C for 18–24 hr under aerobic conditions. Identification of NFGNB was done by Gram staining and MALDI-TOF (Matrix- Assisted Laser Desorption/ Ionization- Time of Flight, Biomerieux- Diagnostics). Antibiotic sensitivity testing was done by Vitek® 2 system (Biomerieux- Diagnostics) using N 281 card. Data was analyzed using SPSS IBM version 16. Out of the total 16,413 non repetitive urine samples that were received in the laboratory, 318 had significant bacteriuria. NFGNB were identified in 108 (33.9%) of all the urine samples with significant bacteriuria. Prevalence of non-fermenters in our study was 0.6%. NFGNB were more frequently isolated in the females and also in the age group of more than 50 years. Eighty five (78.70%) had comorbid conditions. P. aeruginosa and A. baumannii were the most common organism isolated among NFGNB. Pseudomonas aeruginosa isolates showed high susceptibility to imipenem (80.2%) and amikacin (66.6%). NFGNB although seen frequently in females and in age group of 50 years and above, clinical correlation with comorbid condition is essential to label it as uropathogens. Amikacin or imipenem may be the empirical drug of choice.

Objectives: The objective of this study is to assess clinical characteristics, obstetric and perinatal outcome of pregnant women with H1N1 infection. Methods: A retrospective observational study was conducted at a tertiary care teaching hospital. All clinically suspected, probable as well as confirmed cases of swine flu, in pregnancy were included. We analyzed the presenting complaints, condition on admission, criteria for admission in ICU, abnormalities in laboratory reports, course of illness and perinatal outcome. Results: A total of 52 patients in pregnancy and postpartum period were admitted with fever or acute respiratory illness over the period of two years from March 2017 to February 2019. Mean age of patients was 25.88 years. 32 patients were H1N1 positive. In which, 29 were pregnant and 3 patients were postpartum. Mean gestational age was 31weeks. Out of 32 patients, 11 patients were admitted in intensive care unit. There were 4 deaths due to H1N1 illness and all were in 3rd trimester. Conclusion: Acquiring infection in late trimester, late initiation of antiviral treatment and presence of co-morbid illness were high risk factors for developing critical illness. We emphasize that high index of suspicion, early diagnosis; early antiviral therapy and immunization to pregnant women are to reduce the complications, ICU admissions and mortality in this group.

Objective: To evaluate the learning process for laparoscopic hysterectomy (LH) among yuva surgeons. Material and methods: A retrospective comparative study was conducted of all laparoscopic hysterectomies by yuva surgeons (

Background: Mycobacterium tuberculosis is able to survive and persist as an intracellular pathogen by modulating its own metabolism and host immunity. The molecules and mechanisms utilized to accomplish this modulation are not fully understood. The present study elucidates the effects of M. tuberculosis secretory antigens on T-cell-receptor (TCR)/CD28-triggered signaling in Jurkat T-cells. Method: In the present study, intracellular calcium mobilization was investigated in CD3-activated cells in response to M. tuberculosis antigens, Ag85A, early secretory antigenic target-6 (ESAT-6), and H37Rv. The activation of mitogen-activated protein kinases, extracellular signal-regulated kinases 1 and 2 (ERK1/2), and p-38 was also analyzed in CD3- and CD28-activated cells by western blotting. Results: Our results showed CD3-triggered modulations in free intracellular calcium levels in Jurkat T-cells in response to M. tuberculosis antigens. In addition, we also noted M. tuberculosis antigens induced downregulation in phosphorylation of ERK1/2 and p-38. Overall, our results proposed that M. tuberculosis secretory antigens, particularly ESAT-6, impede TCR/CD28-induced signaling events which could be responsible for T-cell unresponsiveness, implicated in the progression of disease. Conclusion: The present study demonstrated M. tuberculosis secretory antigens induced alteration of T-cell signaling pathways in unsensitized Jurkat T-cell line which might be implied in T-cell dysfunctioning during the progression of the disease.

Background Hospital acquired infections are preventable cause for morbidity and mortality worldwide. In the current pandemic era proper implementation of infection control measures can prevent the spread of such infections including SARS-CoV 2. The study was done to identified the source and reason for spread of COVID-19 infection and devise recommendations to halt the progress of infection in a non-COVID area. Methods An outbreak in a non-COVID area of a tertiary care hospital was investigated by the infection control team along with the epidemiologist when they were notified about the rising cases of COVID-19 from Advanced Trauma Center’s (ATC) disaster ward. The time, place and person distribution of the cases were studied. Recommendations based on gaps identified were developed onsite and implemented to control the outbreak. Results The outbreak lasted from 19th December 2020 to 12th January 2021, affecting 34 people (25 patients and 9 health care workers). The attack rate was 9.2%. We identified the causes of current outbreak as compromises in infection prevention measures, high bed patient ratio, irregularities in the ventilation system, overcrowding by patient attendants and communication gaps between nursing officers and doctors. Measures required to control the outbreak were implemented and no cases were reported for 2 weeks following the last positive case. Conclusion Non-COVID areas of hospitals are also at risk of nosocomial outbreaks of SARS-CoV 2 and therefore strict infection prevention measures those designated to COVID areas should be followed in non-COVID zones also to prevent such outbreaks.

Background: Clinical guidelines differ on the recommended number of blood pressure (BP) measurements for hypertension diagnosis in primary health care settings. We assessed the accuracy in identifying high BP (≥140/90 mmHg) and efficiency (mean BP measures per person in one visit) of a practical BP measurement approach against the research standard. Methods: We analyzed data from a national survey in India with three BP measurements for each adult participant (N = 372,110). The research standard (referred to as ‘standard approach’) is measuring three BP and using the mean of the last two. In the practical approach, the first BP reading was used if the measure was 5 mmHg, then we used the third reading. Results: Prevalence of high BP was 15.5% and 14.9% using standard and practical approaches, respectively. The sensitivity, specificity, false positive, and false negative rates of the practical approach were 85.4%, 98.0%, 11.3%, and 2.7% compared to the standard approach. The practical approach was more resource-efficient (mean BPs/person/visit 1.4 versus 3.0 for the standard approach). The practical approach had similar validity, but higher efficiency compared to other internationally recommended BP measurement protocols. Conclusion: The practical BP measurement approach has high validity, is simpler and involves a lower measurement burden on health care providers and can improve the utility of BP measurement, hypertension diagnosis, and management in busy primary health care settings.

Background: India has a high burden of hypertension. While the private sector provides 70% of out-patient care in the country, a significant proportion of patients seeking care from the public sector buy drugs from private markets. This study aimed to describe India’s private sector antihypertensive drugs market at the national and state levels over 2016–2018. Methods: Antihypertensive drugs sales in India from 2016–2018 were analysed using a large nationally representative dataset for the private pharmaceuticals market. In addition, data for five states (Punjab, Madhya Pradesh, Kerala, Telangana, and Maharashtra) that were the foci of a large hypertension control program were studied. Results: The Indian hypertension drug market grew at a rate of 6.9% from 2016 to 2018 with a total of 21,066 million pills sales in 2018. Single-pill combinations (SPCs) contributed to 39.1% of total sale volumes. The market comprised of 182 different antihypertensive drugs including 134 SPCs. Total volume of sales covered a maximum of 26% of treatment need for the estimated population with hypertension. Two-drug SPCs had the highest market share (36%), followed by calcium channel blockers (18%), beta-blockers (16%) and angiotensin receptor blockers (14%). Among SPCs, amlodipine+atenolol had highest sales (9.8%). Twenty-five drugs, a mix of single drugs and SPCs, accounted for 80% of total sales. There were large state-to-state variations in sales per capita, preferred therapeutic classes and drugs. Conclusions: Despite the large antihypertensive drugs market, there exists a high unmet need for treatment in India. Inter-state differences in product sales indicate variable treatment practices, underscoring the need for private sector engagement to improve hypertension care practices aligned with national and international guidelines. SPCs contributed to a large share of the private market and inclusion of select antihypertensive SPCs in the national list of essential medications should be considered for the public health system.

Abstract Background Leprosy is an ideal human disease to study T cell regulation as patients show correlation between cytokine skewed Th1-Th2 responses and clinical forms of the disease. The Role of transcription factors on the modulation of Th1 and Th2 responses by M. leprae antigens has not been adequately studied. In the present study, we studied the effect of M. leprae antigens on transcription factors STAT-4, STAT-6 and CREB and their correlation with Th1/Th2 cell mediated immune responses in leprosy. Methods Leprosy patients of both categories of tuberculoid leprosy (BT/TT) and lepromatous leprosy (BL/LL) were selected from the OPD of NJ1L & OMD, (ICMR), Agra and healthy individuals (H) were chosen from the staff and students working in the institute. Peripheral blood mononuclear cells (PBMCs) of the study subjects were stimulated with M. leprae antigens (WCL, MLSA, and PGL-1). Sandwich ELISA was done in the culture supernatants of healthy and leprosy patients to detect IL-4, IL-10 and IFN-γ. Further, expression of IFN-γ and IL-4 and activation of STAT4, STAT6 and CREB transcription factors in CD4+ T cell with or without stimulation of M. leprae antigens was investigated by flow cytometry. Results Lepromatous leprosy patients showed significantly lower IFN-γ and higher IL-4 levels in culture supernatant and significantly low expression of IFN-γ and higher expression of IL-4 by CD4+ T cells than healthy individuals with or without antigenic stimulation. Antigenic stimulation significantly increased IL-10 in BL/LL patients but not in BT/TT patients or healthy individuals. PGL-1 stimulation led to significantly higher activation of STAT-6 in BT/TT and BL/LL patients in comparison to healthy individuals. All the three antigens led to activation of CREB in healthy and BT/TT patients but not in BL/LL patients. Conclusion Our findings show that M. leprae antigens differentially modulate activation of T cell transcription factors STAT-4/STAT-6 and CREB. These transcription factors are well known to regulate Th1 and Th2 mediated immune response which in turn could play vital role in the clinical manifestations of leprosy. These observations may help to determine how these T cell transcription factors affect the development of immune dysfunction and whether these new pathways have a role in immunomodulation in intracellular diseases like leprosy and TB.

Background: Despite the availability of effective and affordable treatments, only 14% of hypertensive Indians have controlled blood pressure. Increased hypertension treatment coverage (the proportion of individuals initiated on treatment) and adherence (proportion of patients taking medicines as recommended) promise population health gains. However, governments and other payers will not invest in a large-scale hypertension control program unless it is both affordable and effective. Objective: To investigate if a national hypertension control intervention implemented across the private and public sector facilities in India could save overall costs of CVD prevention and treatment. Methods: We developed a discrete-time microsimulation model to assess the cost-effectiveness of population-level hypertension control intervention in India for combinations of treatment coverage and adherence targets. Input clinical parameters specific to India were obtained from large-scale surveys such as the Global Burden of Disease as well as local clinical trials. Input hypertensive medication cost parameters were based on government contracts. The model projected antihypertensive treatment costs, avoided CVD care costs, changes in disability-adjusted life year (DALYs) and incremental cost per DALY averted (represented as incremental cost-effectiveness ratio or ICER) over 20 years. Results: Over 20 years, at 70% coverage and adherence, the hypertension control intervention would avert 1.68% DALYs and be cost-saving overall. Increasing adherence (while keeping coverage constant) resulted in greater improvement in cost savings compared to increasing coverage (while keeping adherence constant). Results were most sensitive to the cost of antihypertensive medication, but the intervention remained highly cost-effective under all one-way sensitivity analyses. Conclusion: A national hypertension control intervention in India would most likely be budget neutral or cost-saving if the intervention can achieve and maintain high levels of both treatment coverage and adherence.

This study aimed to treat hepatocellular ailments with biologically prepared silver nanoparticle (AgNPs). AgNPs were formulated using Morus alba leaf extract and their synthesis and characterization were determined by UV–visible spectroscopy, Transmission Electron Microscope (TEM), Scanning Electron microscope (SEM), X-ray diffraction (XRD), Fourier transform infrared spectroscopy (FT-IR) and Zeta analysis. In vitro studies on HepG2 cell lines for cytotoxic effect and in vivo studies in a rat model for hepatoprotective effect were carried out using biologically prepared AgNPs as curing agents. Dose response cytotoxicity on hepatic cancer (HepG2) cells was confirmed by 3-(4, 5-dimethyl thiazole-2-yl)-2, 5-diphenyl tetrazolium (MTT) assay. The inhibitory concentrations (IC50) were found to be 20 μg/mL and 80 μg/mL for AgNPs and M. alba leaf extract respectively against HepG2 cells at 24 h incubation. In addition, hepatotoxicity in Wistar rats (180 ± 10 g) was induced by intraperitoneal injection of N-nitrosodiethylamine (NDEA) and were treated with different doses of AgNPs (25, 50, 100 μg/kg). NDEA administration showed a significant rise in the biochemical parameters whereas the levels of enzymic antioxidants were decreased. Obtained results revealed that the elevated levels of Liver Function Test (LFTs) biomarkers were significantly reversed and the antioxidant levels were significantly recouped towards normal after the conjoint treatment of AgNPs in a dose-dependent manner. Thus green synthesized AgNPs showed a promising curing effect on hepatocellular ailments. Keywords: Morus alba, Silver nanoparticles, N-Nitrosodiethylamine, HepG2, Liver

INTRODUCTION: Invasive pulmonary aspergillosis (IPA) is a major cause of morbidity and mortality in patients with hematological malignancies. In recent years, testing for values of galactomannan (GM) in serum and bronchoalveolar lavage (BAL) fluid has been investigated as a diagnostic test for IPA for such patients, but global experience and consensus on optical density (OD) cutoffs, especially for BAL galactomannan remains lacking. METHODS: We performed a prospective case–control study to determine an optimal BAL GM OD cutoff for IPA in at-risk patients. Cases were subjects with hematological diagnoses who met established revised definitions for proven or probable IPA established by the European Organization for Research and Treatment of Cancer/Invasive Fungal Infections Cooperative Group (EORTC/MSG, 2008), without the use of BAL GM results. Exclusion criteria included the use of piperacillin/tazobactam and use of antifungals that were active against Aspergillus spp. before bronchoscopy. There were two control groups: patients with hematological diagnoses not meeting definitions for proven or probable IPA and patients with nonhematological diagnoses with no evidence of aspergillosis. Following bronchoscopy and BAL, GM testing was performed using the Platelia Aspergillus seroassay in accordance with the manufacturer’s instructions. RESULTS: There were 51 cases and 20 controls. Cases had higher BAL fluid GM OD indices (ODIs) (mean: 1.27 and range: 0.4–3.78) compared with controls (mean: 0.26 and range: 0.09–0.35). Receiver operating characteristic analysis demonstrated an optimum ODI cutoff of 1.0, with high specificity (100%) and sensitivity (87.5%) for diagnosing IPA. CONCLUSIONS: Our results support BAL GM testing as a reasonably safe test with higher sensitivity compared to serum GM testing in at-risk patients with hematological diseases. A higher OD cutoff is necessary to avoid overdiagnosis of IPA.

Background: Competitive examinations, particularly in mathematics, have made emotional stress a major problem for preuniversity students, emotions like aggression toward fellow students and teachers increase. Mindfulness is a quality that reduces both emotional stress and aggression, so increasing mindfulness should be helpful. Aims: To study the effects of Yoga Pranayama (YP) and Vedic Mathematics (VM) on mindfulness, aggression, and emotion regulation. Methods: Participants were 12th graders attending a preuniversity college in Chikkamagaluru, India, of both genders. Exclusion criteria included major psychological problems. Three classes were arbitrarily assigned to one of three interventions, which consisted of 15 days each of 30 min daily instruction in YP, Group 1, VM, Group 2, or 30 min ordinary class work, Group 3, the control group. Assessments were made using the Mindfulness Attention Awareness Scale, the Nonphysical Aggression Scale from Pittsburgh Youth Study, and the Emotion Regulation Questionnaire. Statistical Analysis Used: SPSS 19.0. Results: Mindfulness, aggression, and negative emotional regulation changed significantly for the YP group, while mindfulness alone improved significantly for the VM group. No group changed on positive emotion regulation. Controls apparently improved on aggression. An interesting post hoc correlation analysis is also reported, among other things directly linking increased mindfulness to decreased aggression. Conclusions: The study showed positive effects of traditional methods of decreasing emotional pressure on students facing preuniversity mathematics examinations. Increasing mindfulness is considered a way of increasing emotion regulation, so the failure of this study to provide evidence for that is of interest.

Context: Many children have low self-confidence in mathematics, leading to math anxiety, disturbed cognitive skills, and reduction of the quality of their educational experience. Aims: This study aimed to compare methods of reducing such anxiety and improving cognitive skills using pranayama; and second, introducing pattern recognition in problem solving, using methods of Vedic Mathematics. These methods were chosen because pranayamas are well-established, standardized means of anxiety reduction for any stressful condition, offering a precise standard for comparison, while, Vedic Mathematics shortens and facilitates calculations. Settings and Design: The study design was a randomized controlled trial with three groups: Yoga pranayama (YP), Vedic Mathematics (VM), and controls (CG) taking 12th grade students from a private preuniversity college in India. Method: Intervention was 15 days each of 30 min daily instruction in either selected YP or VM for the two experimental groups. All the three groups received conventional math training every day. Exclusion criteria were major psychological problems. Assessments used the Mathematics Anxiety Rating Scale Revised and Children's Cognitive Assessment Questionnaire. Statistical Analysis Used: SPSS 19.0 was used for statistical analysis. Results: The experimental groups improved on all subscales of both tests, p < 0.001: the VM group improving more on the first test and the pranayama group performing better on the second test. Controls showed no improvements. Conclusion: Introducing pranayama and VM methods as teaching aids would improve cognitive skills and reduce math anxiety and offer a means to improve examination results, as later demonstrated.

This study highlights the major trust areas, where the medical tourists are considering India as the country of choice. This study revolves around highlighting the reasons for which medical tourists recognize India as the perfect destination. The study investigates the framework of Medical Tourism in India, as the platform for medical tourists who seek low cost treatments with less waiting time. The study also revolves around identifying the core competencies of Indian Medical Tourism market, which makes it as the strategic thrust for the future growth drivers of the healthcare industry. The study is based upon the data collected through primary research, as well as secondary research from hospitals website, India’s Ministry of Health website and from the website of National Association of Health Tourism.

Reduced graphene oxide (RGO) was synthesized in this research via Tour’s method for the use of filler in the hydrogel matrix. The copolymerization of N,N-dimethylacrylamide (DMA) onto the gum tragacanth (GT) was carried out to develop gum tragacanth-cl-N,N-dimethylacrylamide (GT-cl-poly(DMA)) hydrogel using N,N’-methylenebisacrylamide (NMBA) and potassium persulfate (KPS) as cross-linker and initiator correspondingly. The various GT-cl-poly(DMA) hydrogel synthesis parameters were optimized to achieve maximum swelling of GT-cl-poly(DMA) hydrogel. The optimized GT-cl-poly(DMA) hydrogel was then filled with RGO to form reduced graphene oxide incorporated gum tragacanth-cl-N,N-dimethylacrylamide (GT-cl-poly(DMA)/RGO) hydrogel composite. The synthesized samples were used for competent adsorption of Hg2+ and Cr6+ ions. Fourier transform infrared, X-ray powder diffraction, field emission scanning electron microscopy, energy-dispersive X-ray spectroscopy were used to characterize the gum tragacanth-cl-N,N-dimethylacrylamide hydrogel and reduced graphene oxide incorporated gum tragacanth-cl-N,N-dimethylacrylamide hydrogel composite. The experiments of adsorption-desorption cycles for Hg2+ and Cr6+ ions were carried out to perform the reusability of gum tragacanth-cl-N,N-dimethylacrylamide hydrogel and reduced graphene oxide incorporated gum tragacanth-cl-N,N-dimethylacrylamide hydrogel composite. From these two samples, reduced graphene oxide incorporated gum tragacanth-cl-N,N-dimethylacrylamide exhibited high adsorption ability. The Hg2+ and Cr6+ ions adsorption by gum tragacanth-cl-N,N-dimethylacrylamide and reduced graphene oxide incorporated gum tragacanth-cl-N,N-dimethylacrylamide were best suited for pseudo-second-order kinetics and Langmuir isotherm. The reported maximum Hg2+ and Cr6+ ions adsorption capacities were 666.6 mg g-1 and 473.9 mg g-1 respectively.

BACKGROUND:In 2010, WHO recommended the use of new short-course treatment regimens in kala-azar elimination efforts for the Indian subcontinent. Although phase 3 studies have shown excellent results, there remains a lack of evidence on a wider treatment population and the safety and effectiveness of these regimens under field conditions. METHODS:This was an open label, prospective, non-randomized, non-comparative, multi-centric trial conducted within public health facilities in two highly endemic districts and a specialist referral centre in Bihar, India. Three treatment regimens were tested: single dose AmBisome (SDA), concomitant miltefosine and paromomycin (Milt+PM), and concomitant AmBisome and miltefosine (AmB+Milt). Patients with complicated disease or significant co-morbidities were treated in the SDA arm. Sample sizes were set at a minimum of 300 per arm, taking into account inter-site variation and an estimated failure risk of 5% with 5% precision. Outcomes of drug effectiveness and safety were measured at 6 months. The trial was prospectively registered with the Clinical Trials Registry India: CTRI/2012/08/002891. RESULTS:Out of 1,761 patients recruited, 50.6% (n = 891) received SDA, 20.3% (n = 358) AmB+Milt and 29.1% (n = 512) Milt+PM. In the ITT analysis, the final cure rates were SDA 91.4% (95% CI 89.3-93.1), AmB+Milt 88.8% (95% CI 85.1-91.9) and Milt+PM 96.9% (95% CI 95.0-98.2). In the complete case analysis, cure rates were SDA 95.5% (95% CI 93.9-96.8), AmB+Milt 95.5% (95% CI 92.7-97.5) and Milt+PM 99.6% (95% CI 98.6-99.9). All three regimens were safe, with 5 severe adverse events in the SDA arm, two of which were considered to be drug related. CONCLUSION:All regimens showed acceptable outcomes and safety profiles in a range of patients under field conditions. Phase IV field-based studies, although extremely rare for neglected tropical diseases, are good practice and an important step in validating the results of more restrictive hospital-based studies before widespread implementation, and in this case contributed to national level policy change in India. TRIAL REGISTRATION:Clinical trial is registered at Clinical trial registry of India (CTRI/2012/08/002891, Registered on 16/08/2012, Trial Registered Prospectively).

Medicopsis romeroi (M. romeroi) (syn. Pyrenochaeta romeroi) is a rare melanized fungus causing subcutaneous/localized invasive phaeohyphomycosis in immunocompromised patients. We present a rare case of subcutaneous phaeohypho-mycotic cyst caused by M.romeroi in a diabetic male with lepromatous leprosy. Molecular identification was performed by sequencing of Internal Transcribed Spacer (ITS) region and D1/D2 region of Large Ribosomal Subunit (LSU).

AmBisome therapy for VL has an excellent efficacy and safety profile and has been adopted as a first-line regimen in Bangladesh. Second-line treatment options are limited and should preferably be given in short course combinations in order to prevent the development of resistant strains. Combination regimens including AmBisome, paromomycin and miltefosine have proved to be safe and effective in the treatment of VL in India. In the present study, the safety and efficacy of these same combinations were assessed in field conditions in Bangladesh.The safety and efficacy of three combination regimens: a 5 mg/kg single dose of AmBisome + 7 subsequent days of miltefosine (2.5 mg/kg/day), a 5 mg/kg single dose of AmBisome + 10 subsequent days of paromomycin (15 mg/kg/day) and 10 days of paromomycin (15 mg/kg/day) + miltefosine (2.5 mg/kg/day), were compared with a standard regimen of AmBisome 15 mg/kg given in 5 mg/kg doses on days 1, 3 and 5. This was a phase III open label, individually randomized clinical trial. Patients from 5 to 60 years with uncomplicated primary VL were recruited from the Community Based Medical College Bangladesh (CBMC,B) and the Upazila Health Complexes of Trishal, Bhaluka and Fulbaria (all located in Mymensingh district), and randomly assigned to one of the treatments. The objective was to assess safety and definitive cure at 6 months after treatment.601 patients recruited between July 2010 and September 2013 received either AmBisome monotherapy (n = 158), AmBisome + paromomycin (n = 159), AmBisome + miltefosine (n = 142) or paromomycin + miltefosine (n = 142). At 6 months post- treatment, final cure rates for the intention-to-treat population were 98.1% (95%CI 96.0-100) for AmBisome monotherapy, 99.4% (95%CI 98.2-100) for the AmBisome + paromomycin arm, 94.4% (95%CI 90.6-98.2) for the AmBisome + miltefosine arm, and 97.9% (95%CI 95.5-100) for paromomycin + miltefosine arm. There were 12 serious adverse events in the study in 11 patients that included 3 non-study drug related deaths. There were no relapses or PKDL up to 6 months follow-up. All treatments were well tolerated with no unexpected side effects. Adverse events were most frequent during treatment with miltefosine + paromomycin, three serious adverse events related to the treatment occurred in this arm, all of which resolved.None of the combinations were inferior to AmBisome in both the intention-to-treat and per-protocol populations. All the combinations demonstrated excellent overall efficacy, were well tolerated and safe, and could be deployed under field conditions in Bangladesh. The trial was conducted by the International Centre for Diarrhoeal Disease Research (ICDDR,B) and the Shaheed Suhrawardy Medical College (ShSMC), Dhaka, in collaboration with the trial sites and sponsored by the Drugs for Neglected Diseases initiative (DNDi).ClinicalTrials.gov NCT01122771.

Most breast cancer patients die due to bone metastasis. Although metastasis accounts for 5% of the breast cancer cases, it is responsible for most of the deaths. Sometimes even before the detection of a primary tumor, most of the patients have bone and lymph node metastasis. Moreover, at the time of death, breast cancer patients have the bulk of the tumor burden in their bones. Therapy options are available for the treatment of primary tumors, but there are minimal options for treating breast cancer patients who have bone metastasis. C-X-C motif chemokine receptor type 2 (CXCR2) receptor-mediated signaling has been shown to play a critical role during bone-related inflammations and its ligands C-X-C motif chemokine ligand 6 (CXCL6) and 8 (CXCL8) aid in the resorption of bone during bone metastasis. In this study, we tested the hypothesis that CXCR2 contributes to mammary tumor-induced osteolysis and bone metastasis. In the present study, we examined the role of both tumor cell-derived and host-derived CXCR2 in influencing mammary tumor cell bone metastasis. For understanding the role of tumor cell-derived CXCR2, we utilized Cl66 CXCR2 knockdown (Cl66-shCXCR2) and Cl66-Control cells (Cl66-Control) and observed a significant decrease in tumor growth and tumor-induced osteolysis in Cl66-shCXCR2 cells in comparison with the Cl66-Control cells. Next, for understanding the role of host-derived CXCR2, we utilized mice with genomic knockdown of CXCR2 (Cxcr2−/−) and injected Cl66-Luciferase (Cl66-Luc) or 4T1-Luciferase (4T1-Luc) cells. We observed decreased bone destruction and metastasis in the bone of Cxcr2−/− mice. Our data suggest the importance of both tumor cell- and host-derived CXCR2 signaling in the bone metastasis of breast cancer cells.