Search

The progressive decline of the anatomical architecture and loss of functional integrity of an individual is aging. Accumulation of degenerative cellular and molecular changes in the aging cells increases the fragility at the cellular and molecular levels. It pushes towards age-associated diseases like Alzheimer's disease, hypertension, cancer, cardiovascular diseases, etc. The impaired T cell function in aging is a leading contributor to increased susceptibility to pathogens, minimized vaccine response, and skewed inflammation. Recent studies about the role of T cells in the remodelling of the immune system have provided ways to examine and explore aging puzzles and their correlation with T cell functions. Here we review the metabolic aspect of T cell function and its possible restoration. IL-7 and mTOR mediated pathways and their association with reactivation of effector T cell function could help understanding the dark side of the compromised adaptive immune system, particularly T cell response, in aging. Understanding these crucial fundamentals could help design and target new molecules to prevent loss of T cell functionality in aging.

OBJECTIVE: The study reports the efficacy of sequential instillations of intralesional percutaneous polidocanol in the treatment of skeletal ABC. The study also analyses the pain relief, recurrence, radiological outcome and complications after percutaneous sclerotherapy. MATERIALS AND METHODS: A total of 43 patients with ABC were managed by fluoroscopy assisted percutaneous intralesional sclerotherapy with 3% Injection Polidocanol under suitable anaesthesia. The pain relief was assessed by Visual Analog Scale (VAS) and the progressive healing of the lesion by Rastogi Classification. Patients were evaluated clinico-radiologically, pre-operatively and at monthly interval for the first three months and then at 6 months, one year and two years follow up. RESULT: The VAS score decreased significantly at six months follow up and was zero (No pain) at one year follow up. Out of 43 patients, 37 patients had Degree I (excellent) residual lesion and 6 patients had degree II (good) lesion at one year follow-up as per Rastogi classification. The lesions resolved completely by two-year follow-up with all 43 patients having Degree (excellent) I resolution. CONCLUSION: Our study highlights the efficacy of percutaneous intralesional polidocanol in the treatment of ABC's. The procedure is safe, simple and effective with excellent outcome. Sclerotherapy is highly beneficial for deep lesions which are difficult to assess and for comorbid patients who are medically unfit for surgery. Our study strongly advocates the use of sclerotherapy as the first line treatment for ABC, considering its clinical and radiological efficacy.

Typhoid fever is an endemic disease in many low-income and middle-income countries. The 2018 WHO position paper recommends that countries should consider typhoid vaccination in high-risk groups and for outbreak control. To address the typhoid vaccine supply and demand gap, a typhoid Vi polysaccharide-diphtheria toxoid (Vi-DT) conjugate vaccine development effort was undertaken to achieve WHO prequalification and contribute to the global supply of typhoid conjugate vaccine. The main aim of this study was to show immune non-inferiority of the Vi-DT vaccine compared with the WHO prequalified Vi polysaccharide-tetanus toxoid (Vi-TT) conjugate vaccine (Typbar TCV; Bharat Biotech India, Hyderabad, India) in participants of various ages from an endemic country.We did an observer-blind, active-controlled, randomised, non-inferiority, phase 3 trial at four hospitals in Kathmandu, Dhulikhel, Dharan, and Nepalgunj in Nepal. Eligible participants were healthy individuals aged 6 months to 45 years for whom informed consent was obtained, were willing to follow the study procedures and were available for the duration of the study. Patients with an acute or chronic illness that could interfere with interpretation of the study endpoints, or who were involved in any other clinical trial were excluded. Participants were randomly assigned (1:1:1:1) by block randomisation (block size of four and eight), stratified by age (6 months to2 years, 2 years to18 years, and 18 years to 45 years), into one of four groups (A-D). Participants in groups A-C received a single dose (25 μg; 0·5 mL) of Vi-DT test vaccine via intramuscular injection from one of three good manufacturing practice lots (group A received lot 1, group B received lot 2, and group C received lot 3), and those in group D received a single dose (25 μg; 0·5 mL) of the Vi-TT vaccine via intramuscular injection. All participants, site staff (except for those who administered the study vaccines), and those assessing the outcomes were masked to group assignment. The co-primary endpoints were: (1) non-inferiority of immunogenicity of the Vi-DT vaccine (pooled groups A-C) versus the Vi-TT vaccine (group D), measured by the anti-Vi IgG seroconversion rate at 4 weeks after vaccination; and (2) the lot-to-lot consistency of the Vi-DT vaccine, measured by immune equivalence of the anti-Vi IgG geometric mean titre (GMT) at 4 weeks after receipt of the three Vi-DT vaccine lots (lot 1 vs lot 2, lot 1 vs lot 3, and lot 2 vs lot 3). Non-inferiority of the Vi-DT vaccine compared with the Vi-TT vaccine was shown if the lower limit of the 97·5% CI for the difference between the seroconversion rates in Vi-DT vaccine groups A-C combined versus Vi-TT vaccine group D was above the predefined non-inferiority margin of -10%. Lot-to-lot immune equivalence was shown if the upper and lower bounds of the two-sided 99·17% CI around the GMT ratio for each pairwise lot-to-lot comparison was between 0·67 and 1·50, which is the predefined equivalence margin recommended by WHO. The co-primary immunogenicity endpoints were assessed in all randomised participants who had received their assigned vaccine and had completed at least one post-baseline immunogenicity assessment. Safety was descriptively summarised by group and age strata, and was assessed in all participants who had received one dose of the investigational vaccine. The trial is registered with ClinicalTrials.gov, NCT03933098.Between Nov 20, 2019, and March 10, 2020, 1854 individuals were screened, of whom 1800 were enrolled and randomly assigned to groups A-D (450 participants in each group). 1786 (99·2%; 443 in group A, 450 in group B, 447 in group C, and 446 in group D) were included in the immunogenicity assessments at 4 weeks post vaccination, and all 1800 participants were included in the safety analysis. In the immunogenicity analysis, the anti-Vi-IgG seroconversion rate in all age strata was 99·33% (97·5% CI 98·61 to 99·68; 1331 of 1340 participants) in Vi-DT vaccine groups A-C and 98·88% (97·10 to 99·57; 441 of 446) in Vi-TT vaccine group D. The difference in seroconversion rates between Vi-DT vaccine groups A-C combined versus Vi-TT group D was 0·47% (97·5% CI -0·68 to 1·61), indicating non-inferiority of the Vi-DT vaccine. Anti-Vi-IgG GMT ratios at 4 weeks post-vaccination were 1·02 (99·17% CI 0·85 to 1·22) for lot 1 versus lot 2, 1·02 (0·85 to 1·23) for lot 1 versus lot 3, and 1·01 (0·84 to 1·21) for lot 2 versus lot 3, indicating lot-to-lot equivalence according to the predefined, WHO-recommended equivalence margin. The proportion of participants reporting adverse events was similar between Vi-DT vaccine groups A-C and Vi-TT vaccine group D; 260 (19·3%) of 1350 participants in Vi-DT vaccine groups A-C and 115 (25·6%) of 450 in Vi-TT vaccine group D reported solicited adverse events within 7 days after vaccination, and 208 (15·4%) in Vi-DT vaccine groups A-C and 76 (16·9%) in Vi-TT vaccine group D reported unsolicited adverse events within 4 weeks after vaccination. Seven serious adverse events (four [0·3%] participants in Vi-DT vaccine groups A-C and three [0·7%] in Vi-TT vaccine group D), including one death in the Vi-TT vaccine group, were reported during the 24-week follow-up period, none of which were considered related to the investigational product.When administered as a single dose, the Vi-DT test vaccine was safe, immunogenic, and non-inferior to the Vi-TT vaccine at 4 weeks post vaccination. Equivalent immunogenicity of the three lots of Vi-DT vaccine was also shown, supporting the manufacturing process of this vaccine. Once prequalified by WHO, this vaccine could be an option for purchase by UN agencies.The BillMelinda Gates Foundation.For the Nepali translation of the abstract see Supplementary Materials section.

We performed a retrospective observational study to analyze the neurological recovery pattern in patients with a sub-laminar retro-thecal epidural abscess managed at our tertiary apex center from 2014 to 2020. We evaluated the Maximal Spinal Cord Compression (MSCC) ratio on Magnetic Resonance Imaging (MRI), the time interval between the appearance of neurological deficit and the initiation of management, spasticity as per Modified Ashworth Scale, presence of drug resistance, and the Lower Extremity Motor Score (LEMS). All patients were given anti-tubercular chemotherapy. We surgically managed 8 patients of which 6 required decompression alone, while 2 patients required additional instrumentation. 2 patients were managed conservatively of which 1 responded favorably to conservative treatment while the other patient showed a worsening of neurology following the detection of drug resistance and abrupt discontinuation of chemotherapy. The mean LEMS on admission was 20.2, which improved to 38.5 at the end of 1 year (p-value 0.05).

Link prediction is a fundamental task in network theory due to the wide variety of applications in different domains. The objective of link prediction is to find the future links that are likely to be seen in some future time. In this paper, we propose a novel embedding-based technique that utilizes the concept of the Skip-gram framework. An embedding-based method embodies the learning of feature representations of nodes or links in a network. Our method jointly exploits the Skip-gram framework and max aggregator for edge embedding tasks. To test the effectiveness of the proposed method, we have conducted experiments on large size real-world networks. In the experimental evaluation, we have compared the proposed method against both similarity-based and learning-based approaches. The experimental results indicate the effectiveness of the proposed method both in terms of time and accuracy.

Wireless Sensor Network (WSN) is one of the integral part of the present ubiquitous and pervasive computing. The smartness of the applications is incomplete without WSNs. Almost all the scenarios of WSNs require efficient and accurate localization process. However, the main disadvantage of the existing frameworks and algorithms is that they are not so much significant with the trust of the beacon nodes which are integral part of WSNs. This must be ensured for localization. In our present solution, we consider this issue. It is obvious to have the malicious nodes in the hostile environment of WSN operations. Our proposed solution, therefore, address this challenge and provides a trust-based framework for secure localization. It focus on the trust assessment algorithm and blockchain generation. In the localization process, trust values of each beacon node are computed based on different trust metrics and the corresponding weights are dynamically adjusted. Subsequently, for the mining process, higher trusty beacon nodes are only selected. This two-step approach ensures an updated blockchain with reliability and consistent trust values of all beacon nodes. We perform a set of simulations to validate the performance and effectiveness of the proposed algorithm. The results are comparatively analyzed based on localization accuracy, detection of malicious activities, False Positive Rate (FPR), and False Negative Rate (FNR). In all the aspects our solution outperforms the other algorithms.

Marine natural bioactive compounds have chemical diversities, which can be used to develop new potent drugs for various diseases. In this study, Lyngbya sp. (cyanobacterium), was used to explore for its biological potential against inflammation and cancer. (9S,E)-8-ethyl-9-methylnonadec-6-en-3-one (EME), was extracted from Lyngbya sp., purified, and characterized by different spectroscopic techniques. In addition, EME was assessed for the anti-inflammatory potential by Fluorescence Activated Cell Sorting Analysis (FACS) in Lipopolysaccharide (LPS) induced RAW 264.7 macrophage cell lines, and a significant reduction in COX-2 expression was observed. Further, COX-2, TNF-α, iNOS, NF-ĸβ, and IL-1β gene expressions were also analysed in EME treated LPS induced RAW 264.7 cell line by semi-quantitative PCR. Subsequently, to enhance the availability of EME into the cells for the anti-inflammatory potential, it was blended with aminated mesoporous silica nanoparticles (MSNPs). The expressions of COX-2, TNF-α, iNOS, NF-κβ, and IL-1β were significantly downregulated in EME + MSNPs treated LPS induced RAW 264.7 cells. Conclusively, EME combined with MSNPs showed the therapeutic potential of an antiinflammatory agent. Furthermore, the cytotoxic activity of EME was also explored in cervical (HeLa) and liver cancer (HepG2) cell lines; the western blotting results witnessed that EME had induced the expressions of p53, caspase-3, and p21.

Oxidative stress is common consequence of abiotic stress in plants as well as cyanobacteria caused by generation of reactive oxygen species (ROS), an inevitable product of respiration and photosynthetic electron transport. ROS act as signalling molecule at low concentration however, when its production exceeds the endurance capacity of antioxidative defence system, the organisms suffer oxidative stress. A highly toxic metabolite, methylglyoxal (MG) is also produced in cyanobacteria in response to various abiotic stresses which consequently augment the ensuing oxidative damage. Taking recourse to the common lineage of eukaryotic plants and cyanobacteria, it would be worthwhile to explore the regulatory role of glyoxalase system and antioxidative defense mechanism in combating abiotic stress in cyanobacteria. This review provides comprehensive information on the complete glyoxalase system (GlyI, GlyII and GlyIII) in cyanobacteria. Furthermore, it elucidates the recent understanding regarding the production of ROS and MG, noteworthy link between intracellular MG and ROS and its detoxification via synchronization of antioxidants (enzymatic and non-enzymatic) and glyoxalase systems using glutathione (GSH) as common co-factor.