Estimation of Total Saponins and Evaluate Their Effect on in vitro Methanogenesis and Rumen Fermentation Pattern in Wheat Straw Based Diet

The present experiment was carried out to estimate the total saponins and evaluate their effect on methanogenesis and rumen fermentation by in vitro gas production techniques. Three plant material, rough chaff tree seed (Achyranthus aspara, T1), gokhru seed (Tribulus terrestris, T2) and Siris seed (Albizia lebbeck, T3) were selected for present study. The total saponins content in T1, T2 and T3 were 45.75, 25.65 and 48.26% (w/w), respectively. Three levels of each saponins (3, 6 and 9% on DM basis) and wheat straw based (50R:50C) medium fiber diet (200±10 mg) were used for the evaluation of their effect on methanogenesis and rumen fermentation pattern. Results showed the maximum methane reduction (49.66% in term of mM/gDDM) and acetate propionate ration (35.08%) were found in T1 at 6 and 3% levels. Result show that propionate production (mM/ml) was increased; protozoa population decreased (75%) significantly on addition with T3 at 6% level. No significant variation was found in dry matter digestibility in all cases. The present results demonstrate that total saponins extracted from different herbal plants are a promising rumen modifying agent. They have the potential to modulate the methane production, dry matter digestibility and microbial biomass synthesis

Evaluation of temporomandibular joint disorders using cone beam computed tomography

Background: The aim of this study was to evaluate efficacy of segmental cone beam computed tomography (CBCT) in detecting bony changes in condyle and thickness of roof of glenoid fossa in temporomandibular joint (TMJ) disorders.Methods: The study group comprised of 10 temporomandibular disorders (TMD) patients of either sex between the age group of 20-60 years diagnosed as TMDs by clinical evaluation using the research diagnostic criteria was considered. After the clinical examination, radiographic investigations were carried out which included digital OPG, transcranial radiograph and CBCT scan. TMJ Evaluation included: (a) bony changes of the condyle (flattening, erosion, sclerosis, osteophytes, resorption); (b) joint space (normal, increased, reduced, bony contact between the condyle and the mandibular fossa); and (c) bony changes of mandibular fossa (normal, sclerosis, erosion, resorption). The radiographic findings were statistically analysed.Results: Significant difference between OPG, transcranial and CBCT were found for the presence of erosion (P =0.000), thickness of roof of glenoid fossa (P =0.000), deformed contour (P =0.001), joint space (P =0.011), subchondral sclerosis (P =0.011), irregularity of articular surface and eminence (P =0.000), flattening (P =0.050). Conclusions: Using CBCT as imaging technique in our study to detect osseous changes in the TMJ was proved to be effective as compared to the conventional radiographic techniques, the results achieved with CBCT was 100%.The results obtained in our study prove to be a full proof one and it seems to promise to go one step closer to detect progression and severity of the osseous changes in the condylar head and mandibular fossa in patients with TMDs

Clinical profile of dengue fever infection in patients admitted in tertiary care centre Agroha, Hisar, Haryana, India

Background: Dengue infections can result in a wide spectrum of disease severity ranging from an influenza-like illness (dengue fever; DF) to the life-threatening dengue hemorrhagic fever (DHF)/dengue shock syndrome (DSS). The study was aimed to compare the clinical profile of all patients diagnosed with dengue viral infection at MAMC.Methods: This retrospective study included 188 patients infected with dengue virus, age 6 years to 70 years. Laboratory and haematological data were included.Results: Peak of infection occurred in October 2015 and least number of cases were recorded in December 2015. Common clinical symptoms were fever, and abdominal pain. Common haematological abnormalities were thrombocytopenia and leucopoenia. All patients survived. There was no case of dengue hemorrhagic fever or dengue shock syndrome.Conclusions: Significant differences in the clinical profile is possibly because of infection with different serotypes of dengue virus (DENV), concurrent/sequential infection of more than one serotype, and differences in host immune responses associated with host genetic variations

Clinical Study of Granulomatous Mastitis- A Rare Entity

Introduction: Granulomatous Mastitis (GM), a rare and benign disorder, has two forms- Idiopathic Granulomatous Mastitis (IGM) and Specific Granulomatous Mastitis (SGM). IGM is caused without any particular discernable and attributable cause while SGM is caused secondary to tuberculosis, other infectious causes like syphilis, fungal, parasitic infections, corynebacterial; Wegener’s granulomatosis, sarcoidosis, reaction to a foreign body, vasculitis etc. Aim: To identify clinical presentations and to formulate a treatment protocol for patients with granulomatous mastitis. Materials and Methods: This study was a prospective descriptive observational study conducted at Government Wenlock Hospital and Kasturba Medical College Hospital, Attavar, Mangalore, Karnataka, India, from October 2015 to March 2018 on 32 patients admitted to the Department of General Surgery in the study centre, who had a histopathological diagnosis of granulomatous mastitis. All the relevant data of the patients: demographic data and clinical findings, any medical co-morbidities was collected by telephonic interview and case sheets, operative notes were studied thoroughly and the patients were followed up for regression of their signs and symptoms at one month, two months and six months of their hospital visits. Results of microbial cultures or stains, imaging (mammography, ultrasound if done) and biopsy results were collected. All the collected data was analysed by Chi-square test and Fisher’s exact test and the p-values <0.05 was considered significant. Results: Total of 32 female patients (13 patients were in the age group of 31-40 years) were analysed in the present study. A total of 27 (84.4%) had last child birth <5 years back. The patients who presented with a left laterality lesion were 25 (78%) with statistically significant difference. A total of 18 (56%) of the patients had a lesion in the upper outer while 11 (34%) in lower outer quadrant of breast. A total of 29 (90.6 %) of patients, the disease was extending upto the areola region. All the patients had a firm lump and out of these, 25 (78.1%) of the patient presented with a painful lump. Inflammatory skin changes were seen in 20 (62%) of the patients. Retraction of nipple was presented in 26 (81%) of the patients. A total of 19 (59.4%) patients underwent an excision biopsy of the lump and 22 (69%) patients were initiated with Antitubercular Therapy (ATT). Conclusion: Granulomatous mastitis is a highly unpredictable disease with frequent flares and periods of inactivity which may falsely be considered as successful treatment. Due to rare nature of this disease, randomisation of all treatment modalities are availabl

Improving polio vaccination during supplementary campaigns at areas of mass transit in India

<p>Abstract</p> <p>Background</p> <p>In India, children who are traveling during mass immunization campaigns for polio represent a substantial component of the total target population. These children are not easily accessible to health workers and may thus not receive vaccine. Vaccination activities at mass transit sites (such as major intersections, bus depots and train stations), can increase the proportion of children vaccinated but the effectiveness of these activities, and factors associated with their success, have not been rigorously evaluated.</p> <p>Methods</p> <p>We assessed data from polio vaccination activities in Jyotiba Phule Nagar district, Uttar Pradesh, India, conducted in June 2006. We used trends in the vaccination results from the June activities to plan the timing, locations, and human resource requirements for transit vaccination activities in two out of the seven blocks in the district for the July 2006 supplementary immunization activity (SIA). In July, similar data was collected and for the first time vaccination teams also recorded the proportion of children encountered each day who were vaccinated (a new monitoring system).</p> <p>Results</p> <p>In June, out of the 360,937 total children vaccinated, 34,643 (9.6%) received vaccinations at mass transit sites. In the July SIA, after implementation of a number of changes based on the June monitoring data, 36,475 children were vaccinated at transit sites (a 5.3% increase). Transit site vaccinations in July increased in the two intervention blocks from 18,194 to 21,588 (18.7%) and decreased from 16,449 to 14,887 (9.5%) in the five other blocks. The new monitoring system showed the proportion of unvaccinated children at street intersection transit sites in the July campaign decreased from 24% (1,784/7,405) at the start of the campaign to 3% (143/5,057) by the end of the SIA, consistent with findings from the more labor-intensive post-vaccination coverage surveys routinely performed by the program.</p> <p>Conclusions</p> <p>Analysis of vaccination data from transit sites can inform program management changes leading to improved outcomes in polio immunization campaigns. The number of vaccinated children encountered should be routinely recorded by transit teams and may provide a useful, inexpensive alternative mechanism to assess program coverage.</p

H19 Noncoding RNA, an Independent Prognostic Factor, Regulates Essential Rb-E2F and CDK8-β-Catenin Signaling in Colorectal Cancer

The clinical significance of long noncoding RNAs (lncRNAs) in colorectal cancer (CRC) remains largely unexplored. Here, we analyzed a large panel of lncRNA candidates with The Cancer Genome Atlas (TCGA) CRC dataset, and identified H19 as the most significant lncRNA associated with CRC patient survival. We further validated such association in two independent CRC cohorts. H19 silencing blocked G1-S transition, reduced cell proliferation, and inhibited cell migration. We profiled gene expression changes to gain mechanism insight of H19 function. Transcriptome data analysis revealed not only previously identified mechanisms such as Let-7 regulation by H19, but also RB1-E2F1 function and β-catenin activity as essential upstream regulators mediating H19 function. Our experimental data showed that H19 affects phosphorylation of RB1 protein by regulating gene expression of CDK4 and CCND1. We further demonstrated that reduced CDK8 expression underlies changes of β-catenin activity, and identified that H19 interacts with macroH2A, an essential regulator of CDK8 gene transcription. However, the relevance of H19-macroH2A interaction in CDK8 regulation remains to be experimentally determined. We further explored the clinical relevance of above mechanisms in clinical samples, and showed that combined analysis of H19 with its targets improved prognostic value of H19 in CRC

Evaluation of Critical Quality Attributes of a Pentavalent (A, C, Y, W, X) Meningococcal Conjugate Vaccine for Global Use

Towards achieving the goal of eliminating epidemic outbreaks of meningococcal disease in the African meningitis belt, a pentavalent glycoconjugate vaccine (NmCV-5) has been developed to protect against Neisseria meningitidis serogroups A, C, Y, W and X. MenA and X polysaccharides are conjugated to tetanus toxoid (TT) while MenC, Y and W polysaccharides are conjugated to recombinant cross reactive material 197 (rCRM197), a non-toxic genetic variant of diphtheria toxin. This study describes quality control testing performed by the manufacturer, Serum Institute of India Private Limited (SIIPL), and the independent control laboratory of the U.K. (NIBSC) on seven clinical lots of the vaccine to ensure its potency, purity, safety and consistency of its manufacturing. In addition to monitoring upstream-manufactured components, samples of drug substance, final drug product and stability samples were evaluated. This paper focuses on the comparison of the vaccine’s critical quality attributes and reviews key indicators of its stability and immunogenicity. Comparable results were obtained by the two laboratories demonstrating sufficient levels of polysaccharide O-acetylation, consistency in size of the bulk conjugate molecules, integrity of the conjugated saccharides in the drug substance and drug product, and acceptable endotoxin content in the final drug product. The freeze-dried vaccine in 5-dose vials was stable based on molecular sizing and free saccharide assays. Lot-to-lot manufacturing consistency was also demonstrated in preclinical studies for polysaccharide-specific IgG and complement-dependent serum bactericidal activity for each serogroup. This study demonstrates the high quality and stability of NmCV-5, which is now undergoing Phase 3 clinical trials in Africa and India

Pitfalls in assessing stromal tumor infiltrating lymphocytes (sTILs) in breast cancer

Stromal tumor-infiltrating lymphocytes (sTILs) are important prognostic and predictive biomarkers in triple-negative (TNBC) and HER2-positive breast cancer. Incorporating sTILs into clinical practice necessitates reproducible assessment. Previously developed standardized scoring guidelines have been widely embraced by the clinical and research communities. We evaluated sources of variability in sTIL assessment by pathologists in three previous sTIL ring studies. We identify common challenges and evaluate impact of discrepancies on outcome estimates in early TNBC using a newly-developed prognostic tool. Discordant sTIL assessment is driven by heterogeneity in lymphocyte distribution. Additional factors include: technical slide-related issues; scoring outside the tumor boundary; tumors with minimal assessable stroma; including lymphocytes associated with other structures; and including other inflammatory cells. Small variations in sTIL assessment modestly alter risk estimation in early TNBC but have the potential to affect treatment selection if cutpoints are employed. Scoring and averaging multiple areas, as well as use of reference images, improve consistency of sTIL evaluation. Moreover, to assist in avoiding the pitfalls identified in this analysis, we developed an educational resource available at www.tilsinbreastcancer.org/pitfalls.Stromal tumor-infiltrating lymphocytes (sTILs) are important prognostic and predictive biomarkers in triple-negative (TNBC) and HER2-positive breast cancer. Incorporating sTILs into clinical practice necessitates reproducible assessment. Previously developed standardized scoring guidelines have been widely embraced by the clinical and research communities. We evaluated sources of variability in sTIL assessment by pathologists in three previous sTIL ring studies. We identify common challenges and evaluate impact of discrepancies on outcome estimates in early TNBC using a newly-developed prognostic tool. Discordant sTIL assessment is driven by heterogeneity in lymphocyte distribution. Additional factors include: technical slide-related issues; scoring outside the tumor boundary; tumors with minimal assessable stroma; including lymphocytes associated with other structures; and including other inflammatory cells. Small variations in sTIL assessment modestly alter risk estimation in early TNBC but have the potential to affect treatment selection if cutpoints are employed. Scoring and averaging multiple areas, as well as use of reference images, improve consistency of sTIL evaluation. Moreover, to assist in avoiding the pitfalls identified in this analysis, we developed an educational resource available at www.tilsinbreastcancer.org/pitfalls.Peer reviewe

The global burden of cancer attributable to risk factors, 2010-19 : a systematic analysis for the Global Burden of Disease Study 2019

Background Understanding the magnitude of cancer burden attributable to potentially modifiable risk factors is crucial for development of effective prevention and mitigation strategies. We analysed results from the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2019 to inform cancer control planning efforts globally. Methods The GBD 2019 comparative risk assessment framework was used to estimate cancer burden attributable to behavioural, environmental and occupational, and metabolic risk factors. A total of 82 risk-outcome pairs were included on the basis of the World Cancer Research Fund criteria. Estimated cancer deaths and disability-adjusted life-years (DALYs) in 2019 and change in these measures between 2010 and 2019 are presented. Findings Globally, in 2019, the risk factors included in this analysis accounted for 4.45 million (95% uncertainty interval 4.01-4.94) deaths and 105 million (95.0-116) DALYs for both sexes combined, representing 44.4% (41.3-48.4) of all cancer deaths and 42.0% (39.1-45.6) of all DALYs. There were 2.88 million (2.60-3.18) risk-attributable cancer deaths in males (50.6% [47.8-54.1] of all male cancer deaths) and 1.58 million (1.36-1.84) risk-attributable cancer deaths in females (36.3% [32.5-41.3] of all female cancer deaths). The leading risk factors at the most detailed level globally for risk-attributable cancer deaths and DALYs in 2019 for both sexes combined were smoking, followed by alcohol use and high BMI. Risk-attributable cancer burden varied by world region and Socio-demographic Index (SDI), with smoking, unsafe sex, and alcohol use being the three leading risk factors for risk-attributable cancer DALYs in low SDI locations in 2019, whereas DALYs in high SDI locations mirrored the top three global risk factor rankings. From 2010 to 2019, global risk-attributable cancer deaths increased by 20.4% (12.6-28.4) and DALYs by 16.8% (8.8-25.0), with the greatest percentage increase in metabolic risks (34.7% [27.9-42.8] and 33.3% [25.8-42.0]). Interpretation The leading risk factors contributing to global cancer burden in 2019 were behavioural, whereas metabolic risk factors saw the largest increases between 2010 and 2019. Reducing exposure to these modifiable risk factors would decrease cancer mortality and DALY rates worldwide, and policies should be tailored appropriately to local cancer risk factor burden. Copyright (C) 2022 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license.Peer reviewe