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Background: Arthrocentesis of the temporomandibular joint (TMJ) is the unadorned form of surgical therapy which comprises of lavage of inflammatory enzymes and mediators and improve joint mobility and eliminate pain by pressure of the lavage solution in the upper compartment of TMJ. Objectives: The current study was conducted to assess and compare the effectiveness of arthrocentesis with normal saline alone and in conjunction with sodium hyaluronate (SH) injection in the treatment of internal derangement of the TMJ. Methodology: Sixty patients with internal derangement of the TMJ were randomly divided into two equal groups; Group 1 was performed with normal saline and Group 2 with normal saline followed by 1 ml of SH. The patients were followed up after 1 week to check for any postoperative complications and 1, 2, and 3 months for subsequent sessions and changes in subjective and objective variables. Results: The increase in mouth opening from preoperative to 3 months' postoperatively was 4.9 mm for Group 1 and 6.43 mm for Group 2. The change in the pain score (visual analogue scale scale) in Group 1 from the preoperative session to 3 months' follow-up was 7.23–4.1 and in Group 2 was 7.36–3.7. The difference in clicking/popping in Group 1 from preoperative session to 3 months' follow-up was 2.43–1 and in Group 2 was 2.4–0.53. Conclusion: Patients refractory to conservative treatment showed promising results with arthrocentesis with SH than arthrocentesis alone in treatment of TMJ internal derangement.

Background: Dental plaque is a complex ecosystem which consists of densely packed microbial colonies, microbial by-products, salivary glycoproteins and desquamated epithelial cells. Clinical studies have proved the relationship between plaque and periodontal disease. Aim: This study compares the anti-plaque efficacy and anti-inflammatory potential of turmeric gel with 0.2% chlorhexidine gel along with scaling and root planing (SRP). Materials and Methods: One hundred and fifty individuals were selected and divided into three groups for the study. Group A was instructed to use 0.2% chlorhexidine gel, whereas Group B used turmeric gel along with SRP. Participants were assessed for plaque and gingivitis on the 14th and 21st days. Subjective and objective criteria were assessed. The clinical data were recorded and used for statistical analysis to obtain results. Results: The percentage reduction of plaque index (PI) between the chlorhexidine and turmeric gel on 21st day were 74.85 and 65.91 respectively. similarly, the percentage reduction of gingival index (GI) between the chlorhexidine and turmeric gel on 21st day were 58.49 and 62.46 respectively. Conclusion: Turmeric gel shows a slightly lower anti-plaque property in comparison to chlorhexidine gel. Their effect on a reduction of gingival inflammation was equal. It was also noted that turmeric gel showed better acceptability and biocompatibility by the participants.

Aims: The aim of this study was to evaluate and compare canal transportation (CT), centering ability (CA), and volumetric changes in the curved canals prepared using Hyflex Electrical Discharge Machining (HEDM), ProTaper Gold (PG), and NeoEndo Flex rotary file systems through cone-beam computed tomography (CBCT). Materials and Method: Sixty mesiobuccal canals of maxillary molars were selected. Pre- and postinstrumentation CBCT scans were taken in the same position. CT and CA were calculated at 1 mm, 4 mm, and 7 mm from the apex; change in volume for the whole canal was measured and analyzed statistically. Results: The results showed that mean CT of HEDM and NeoEndo was less than PG at all levels, with significant differences at 4 mm and 7 mm. Regarding CA, no significant differences were found among the file systems. PG showed maximum volumetric increase with no statistically significant differences between the groups. Conclusion: All the experimental file systems respected the canal anatomy, although in the middle third, PG showed significantly more CT than HEDM and NeoEndo, whereas in the coronal third, PG showed significantly greater CT than NeoEndo. Regarding CA, no significant differences were found among the file systems. PG showed maximum volume of dentin removal.

Aim: This study was aimed to evaluate and compare the pull-out bond strength of fiber post using glass ionomer cement (GIC), resin-modified glass ionomer cements (RMGIC), self-etch adhesive resin cement, and self-adhesive resin cement in endodontically treated teeth. Materials and Methods: Forty single-rooted teeth with single canal were decoronated, endodontically treated, post space were prepared and divided into four groups (n = 10) based on the cement used for luting the fiber post. Group 1: GIC, Group 2: RMGIC, Group 3: Self etch adhesive resin cement, Group 4: Self-adhesive resin cement. Pull-out test was evaluated for the prepared samples. Statistical analysis was performed using analysis of variance and Tukey's test (P = 0.05). Results: The mean pull-out bond strength of Group 4 was statistically higher than Group 1,2 and 3. Group 1 showed the least bond strength among all the groups. Conclusion: Within the limitation of this study, self-adhesive resin cements provide better bond strength of fiber post to root canal compared to self-etch adhesive resin cement and glass ionomer based cements.

Background: Hidradenitis suppurativa (HS) demonstrates high placebo response rates in clinical trials, possibly due to the natural variability of the disease. No quantification of variability in lesion counts of untreated disease has been undertaken. Objective: To quantify the variability of untreated HS. Methods: Deidentified individual patient data from the placebo arms of PIONEER studies were analyzed, and measurements of within-subject coefficients of variation were examined. Variability was stratified by disease-associated variables (Hurley stage, BMI, sex, smoking, family history) and body site. Results: Analysis of within-subject coefficients of variation demonstrated that half of the participants had a middle spread [difference between 75th and 25th percentiles of the subject's abscess and nodule counts] greater than 33% and 40% of their median abscess and nodule counts, and 25% of the subjects had a middle spread greater than 70% and 78% of their median abscess and nodule counts in PIONEER I and II, respectively. Hurley stage 2 participants had significantly greater within-subject variation than Hurley stage 3 patients. Variation was greater in the axillary and groin regions than in other anatomical locations. Limitations: Limitations include the use of precollected clinical trial data. Conclusion: The within-subject variability of the lesion counts in untreated HS was greater than previously appreciated. This has profound effects on outcome measures and the conduct of future clinical trials of HS.

Otosclerosis (OTSC) is a complex bone disorder of the otic capsule, which causes conductive hearing impairment in human adults. The dysregulation of the signaling axis mediated by the receptor activator of nuclear factor-kappa-B (RANK), RANK ligand (RANKL), and osteoprotegerin has been widely attributed to the context of metabolic bone disorders. While genetic associations and epigenetic alterations in the TNFSF11 gene (RANKL) have been well-linked to metabolic bone diseases of the skeleton, particularly osteoporosis, they have never been addressed in OTSC. This study aimed to assess whether the genetic association of rs1021188 polymorphism in the upstream of TNFSF11 and the DNA methylation changes in its promoter CpG-region reveal the susceptibility of OTSC. Peripheral blood DNA samples were collected from unrelated Tunisian-North African subjects for genotyping (109 cases and 120 controls) and for DNA methylation analysis (40 cases and 40 controls). The gender-stratified analysis showed that the TNFSF11 rs1021188 C/T was associated with OTSC in men (p = 0.023), but not in women (p = 0.458). Individuals with CC genotype were more susceptible to OTSC, suggesting an increased risk to disease development. Using publicly available data, the rs1021188 was within a cluster grouping the subpopulations with African ethnicity. Moreover, 26 loci in the TNFSF11 gene were in linkage disequilibrium with rs1021188, revealing relative similarities between different populations. Significant differences in both DNA methylation and unmethylation status were detected with 4.53- and 4.83-fold decreases in the global DNA methylation levels in female and male OTSC groups, respectively. These changes could contribute to an increased risk of OTSC development. Bioinformatic analyses indicated that each of the rs1021188 variations and the DNA methylation changes in the promoter CpG-sites within TNFSF11 may play an important role in its transcription regulation. To our knowledge, this is the first study that investigates an independent effect of the rs1021188 polymorphism and DNA hypomethylation of TNFSF11 promoter in OTSC. Genetic and epigenetic changes in the regulatory regions of TNFSF11 could offer new molecular insights into the understanding of the complexity of OTSC.

The calibration technique is the process of adjusting weights for the better enhancement of the estimate of the population parameters using auxiliary information. In this manuscript, we have proposed ratio and regression type calibration estimators for the population mean under both correlated and uncorrelated measurement errors. The variances of the proposed calibrated estimators to the first order approximation are obtained and compared their efficiencies. A Monte Carlo simulation study has been carried out to show the effect of measurement errors on the proposed calibrated estimators.

Abstract Background Otosclerosis (OTSC) is among the most common causes of a late-onset hearing loss in adults and is characterized by an abnormal bone growth in the otic capsule. Alteration in the osteoprotegerin (OPG) expression has been suggested in the implication of OTSC pathogenesis. Methods A case-control association study of rs2228568, rs7844539, rs3102734 and rs2073618 single nucleotide polymorphisms (SNPs) in the OPG gene was performed in a Tunisian-North African population composed of 183 unrelated OTSC patients and 177 healthy subjects. In addition, a multilocus association and a meta-analysis of existing studies were conducted. Results Rs3102734 (p = 0.013) and rs2073618 (p = 0.007) were significantly associated with OTSC, which were predominantly detected in females after multiple corrections. Among the OPG studied SNPs, the haplotypes A-A-C-G (p = 0.0001) and A-A-C-C (p = 0.0004) were significantly associated with OTSC in females. Multilocus association revealed that the SNPs: rs2073618 in OPG, rs1800472 in TGFβ1, rs39335, rs39350 and rs39374 in RELN, and rs494252 in chromosome 11 showed significant OTSC-associated alleles in Tunisian individuals. In addition, meta-analysis of the rs2073618 SNP in Tunisian, Indian and Italian populations revealed evidence of an association with OTSC (OR of 0.826, 95% CI [0.691–0.987], p = 0.035). Conclusions Our findings suggest that rs3102734 and rs2073618 variants are associated with OTSC in North African ethnic Tunisian population. Meta-analysis of the rs2073618 in three different ethnic population groups indicated an association with OTSC.

The proviral integration site for Moloney murine leukemia virus (PIM) serine/threonine kinases have an oncogenic and prosurvival role in hematological and solid cancers. However, the mechanism by which these kinases drive tumor growth has not been completely elucidated. To determine the genes controlled by these protein kinases, we carried out a microarray analysis in T‐cell acute lymphoblastic leukemia (T‐ALL) comparing early progenitor (ETP‐ALL) cell lines whose growth is driven by PIM kinases to more mature T‐ALL cells that have low PIM levels. This analysis demonstrated that the long noncoding RNA (lncRNA) H19 was associated with increased PIM levels in ETP‐ALL. Overexpression or knockdown of PIM in these T‐ALL cell lines controlled the level of H19 and regulated the methylation of the H19 promoter, suggesting a mechanism by which PIM controls H19 transcription. In these T‐ALL cells, the expression of PIM1 induced stem cell gene expression (SOX2, OCT‐4, and NANOG) through H19. Identical results were found in prostate cancer (PCa) cell lines where PIM kinases drive cancer growth, and both H19 and stem cell gene levels. Small molecule pan‐PIM inhibitors (PIM‐i) currently in clinical trials reduced H19 expression in both of these tumor types. Importantly, the knockdown of H19 blocked the ability of PIM to induce stem cell genes in T‐ALL cells, suggesting a novel signal transduction cascade. In PCa, increases in SOX2 levels have been shown to cause both resistance to the androgen deprivation therapy (ADT) and the induction of neuroendocrine PCa, a highly metastatic form of this disease. Treatment of PCa cells with a small molecule pan‐PIM‐i reduced stem cell gene transcription and enhanced ADT, while overexpression of H19 suppressed the ability of pan‐PIM‐i to regulate hormone blockade. Together, these results demonstrate that the PIM kinases control the level of lncRNA H19, which in turn modifies stem cell gene transcription regulating tumor growth.

Introduction Delineation of variant anatomy in celiac trunk and superior mesenteric artery including its origin and branching pattern and variations in branching pattern of hepatic artery in patients of hepatopancreaticobiliary malignancy with the use of mutidetector CT (computed tomography) angiograpgy was performed. Materials and Methods All CT examinations were performed on a 64-multidetector computed tomography (MDCT) scanner. Technical features of multislice computed tomography (MSCT) are as follows: 64 mm × 1 mm collimation, minimum slice thickness of 0.625, gantry rotation time of 320 ms, 120 kV, and 320 mAs. CT angiography was performed with intravenous (IV) administration of nonionic contrast material, that is, iodixanol (Visipaque). The contrast medium and saline solution were injected with a Medrad power injector at 3 mL/sec through an 18-gauge plastic intravenous catheter placed in an antecubital vein in most of the cases. Contrast medium volumes varied between 100 and 150 mL at 1.5 mL/kg. Images were obtained in triphasic pattern at arterial (20–30 seconds), portal (60–70 seconds), and equilibrium (at 3 minutes) phases. Results Five types of celiac axis anatomic variations and nine type of variants in celiac axis branching was found in the study sample of 124 patients. Classical celiac axis anatomy was seen in 92.7% of the cases, while the five types of variation in branching were found in nine patients. Majority of cases showed pattern I (59.6%) followed by patterns V (12.1%), II (9.7%), and III (8.9%). There were three (2.4%) cases each showing pattern VIII and AA, and two (1.6%) cases each showing patterns IV and VI, respectively. There was one (0.8%) case each showing pattern VII and IX. A total of three (2.4%) cases showed right hepatic artery arising from celiac axis. Conclusion We conclude that most common pattern of celiac axis and superior mesenteric artery (SMA) branching is classical pattern (92.7%) which is in concordance with literature. Type-I pattern of hepatic artery branching was most common (59.6%), similar to that documented in literature. Although the most common variation in our study is type V (12.1%), followed by types II (9.7%) and III (8.9%), the most common variation in most of the literature was found to be type III. CT angiography hence is an excellent diagnostic modality for depiction of arterial anatomic variations and provides a roadmap for surgical treatment.

Abstract Background Pay for performance (P4P) schemes provide financial incentives to health workers or facilities based on the achievement of pre-specified performance targets and have been widely implemented in health systems across low and middle-income countries (LMICs). The growing evidence base on P4P highlights that (i) there is substantial variation in the effect of P4P schemes on outcomes and (ii) there appears to be heterogeneity in incentive design. Even though scheme design is likely a key determinant of scheme effectiveness, we currently lack systematic evidence on how P4P schemes are designed in LMICs. Methods We develop a typology to classify the design of P4P schemes in LMICs, which highlights different design features that are a priori likely to affect the behaviour of incentivised actors. We then use results from a systematic literature review to classify and describe the design of P4P schemes that have been evaluated in LMICs. To capture academic publications, Medline, Embase, and EconLit databases were searched. To include relevant grey literature, Google Scholar, Emerald Insight, and websites of the World Bank, WHO, Cordaid, Norad, DfID, USAID and PEPFAR were searched. Results We identify 41 different P4P schemes implemented in 29 LMICs. We find that there is substantial heterogeneity in the design of P4P schemes in LMICs and pinpoint precisely how scheme design varies across settings. Our results also highlight that incentive design is not adequately being reported on in the literature – with many studies failing to report key design features. Conclusions We encourage authors to make a greater effort to report information on P4P scheme design in the future and suggest using the typology laid out in this paper as a starting point.

Introduction The diagnosis of anemia in pregnancy should be early to prevent complications to mother and baby. It should be simple and safe, and therefore feasibility of reticulocyte parameters may prove beneficial in this regard. Newer reticulocyte parameters have not been studied extensively especially in pregnancy. The present study was conducted to evaluate reticulocyte hemoglobin content (Ret-He), immature reticulocyte fraction, and reticulocyte count and to compare them with serum ferritin, mean corpuscular volume (MCV), and mean corpuscular hemoglobin (MCH) in assessment anemia in pregnancy. Material and Methods Prospective study included first trimester pregnant females where hemoglobin, MCV, and MCH were categorized and statistically analyzed with serum ferritin and reticulocyte parameters. Results The study included 155 first trimester pregnant females showing statistical difference in Ret-He between all categories of hemoglobin and MCV (p < 0.05). ROC curve analysis using MCV < 83 fl and MCH

Abstract Approximately one‐third of Merkel cell carcinoma (MCC) patients eventually develop distant metastatic disease. Little is known about whether the location of the primary lesion is predictive of initial distant metastatic site, or if survival likelihood differs depending on the metastatic site. Such data could inform imaging/surveillance practices and improve prognostic accuracy. Multivariate and competing‐risk analyses were performed on a cohort of 215 MCC patients with distant metastases, 31% of whom had two or more initial sites of distant metastasis. At time of initial distant metastasis in the 215 patients, metastatic sites (n = 305) included non‐regional lymph nodes (present in 41% of patients), skin/body wall (25%), liver (23%), bone (21%), pancreas (8%), lung (7%), and brain (5%). Among the 194 patients who presented with MCC limited to local or regional sites (stage I‐III) but who ultimately developed distant metastases, distant progression occurred in 49% by 1 year and in 80% by 2 years following initial diagnosis. Primary MCC locations differed in how likely they were to metastasize to specific organs/sites (P

Background: Endemic fluorosis is one of the major health problems in India. About 96% of the fluoride found in the body is in bones and teeth. When ingested in adequate quantities, fluoride is beneficial for teeth by reducing the level of dental caries, whereas the ingestion of fluoride in higher concentrations may cause fluorosis. Objectives: The objective of the study was to find the prevalence of dental fluorosis in school-going children of 6–14 years in Greater Noida City, residing there since birth. The severity of fluorosis was determined after estimating the fluoride concentration in drinkable groundwater. The distribution of dental fluorosis was then compared according to various variables. Materials and Methods: A sample of 1516 school-going children, residing in the Greater Noida since childhood and consuming the groundwater, were taken across various schools from all five directions. These children were examined for dental fluorosis according to the Dean's criteria for assessment. Results: The prevalence of dental fluorosis in 6–14-year-old school-going children was 69.9%. A stepwise increase in prevalence was noted with a corresponding rise in the water fluoride content in different zones of the city. Conclusion: The prevalence of dental fluorosis was found to be 69.9% with the groundwater concentration gradient ranging from 1.6 to 2.4 ppm.

Abstract Introduction Although controversial, pre-emptive analgesia has shown some promise in preventing altered pain perception and reducing pain amplification after surgery. Hence, it has the potential to be more effective than a similar analgesic regimen started after surgery with an appropriate combination of patient category and analgesic modality. Hence, the present study was undertaken to evaluate the effect of preventive epidural analgesia in reducing pain severity and duration after bilateral single-stage knee arthroplasty. Methods Fifty patients, 18–70 years, with American Society of Anesthesiologists physical status class I & II posted for bilateral single-stage knee replacement under regional anesthesia were randomly allocated into preventive versus postoperative epidural analgesia group to compare severity of post-operative pain, analgesic consumption, day of mobilization, C-reactive protein (CRP) levels, and hospital stay. Results The pain score after surgery [2.0 (1.5, 2.0); 3.0 (1.5, 3.0), p = 0.005] and day of mobilization [(2. 92 ± 0. 28; 3. 31 ± 0. 48; p value 0.02)] were significantly lesser in the preventive epidural group. However, there was no difference in the hospital stay (9.92 ± 3.71 and 9.00 ± 2.12, p = 0.95) and analgesic consumption (65.38 ± 37.55 and 73.08 ± 43.85, p = 0.30). The preventive group had a larger drop in CRP and experienced a lesser number of days with pain after surgery as compared to the controls [(64.29 ± 21.29); (142.37 ± 80.04), p = 0.0001]. Six patients in the preemptive group (24%) and 13 of the control group (24 vs. 56.5%; p = 0.02) had chronic postsurgical pain. Conclusions Preventive epidural analgesia reduces the severity and number of chronic pain days after bilateral single-stage knee replacement. Trial Registration The study was registered in the Indian national registry (CTRI/2017/03/008240 on 28/03/2017).

Background: Tumor necrosis factor-alpha (TNF-α), a ” major inflammatory cytokine,” not only plays an important role in periodontal destruction but also is extremely toxic to the host. Till date, there are not many studies comparing the levels of TNF-α in serum and its relationship to periodontal disease. Aim: Our study aimed to compare the serum TNF-α among the two study groups, namely, healthy controls and chronic periodontitis patients and establish a correlation between serum TNF-α and various clinical parameters. Hence, an attempt is made to estimate the level of TNF-α in serum, its relationship to periodontal disease and to explore the possibility of using the level of TNF-α in serum as a biochemical ” marker” of periodontal disease. Materials and Methods: Forty individuals participated in the study and were grouped into two subgroups. Group A – 20 systemically and periodontally healthy controls. Group B – twenty patients with generalized chronic periodontitis. The serum samples were assayed for TNF-α levels by enzyme-linked immunosorbent assay method. Results: The mean serum TNF-α cytokines for Group B Generalized chronic periodontitis (GCP) was 2.977 ± 1.011, and Group A (healthy) was 0.867 ± 0.865. The range of serum TNF-α was from (0.867 to 2.977). Serum TNF-α cytokines had highly significant correlation with all clinical parameters (plaque index, probing pocket depth, clinical attachment loss, and gingival index) among all study participants (P = 0.001). Conclusion: These observations suggest a positive association between periodontal disease and increased levels of TNF-α in serum. It can be concluded that there is a prospect of using the estimation of TNF-α in serum as a ” marker” of periodontal disease in future. However, it remains a possibility that the absence or low levels of TNF-α in serum might indicate a stable lesion and elevated levels might indicate an active site but only longitudinal studies taking into account, the disease ” activity” and ” inactivity” could suggest the possibility of using TNF-α in serum as an ” Indicator” of periodontal disease.

A new-onset acute kidney injury (AKI) after arthroplasty impairs rehabilitation and outcome. A prior knowledge of risk factors contributes to a planned preventive management and prognostication. Although many studies have addressed the issue, our objective was to perform a meta-analysis to bring a consensus on the perioperative risk factors promoting AKI postoperatively. We conducted a systematic review and meta-analysis of observational studies reporting risk factors with odds of development of AKI according to the existing criteria after hip or knee replacement surgery. We searched the PubMed and Google Scholar databases for free English articles published until June 2018. Two authors independently screened the articles and extracted data. Discrepancies were resolved by consensus or consulting the third author. Methodological quality of the articles was assessed using the Newcastle-Ottawa Scale. A total of five studies were included in this meta-analysis. The following risk factors were found to contribute to new kidney injury: advanced age; male gender; preoperative liver, cardiac, or kidney diseases; presence of heart failure; American Society of Anesthesiologists grade ≥ 3; requirement of perioperative blood transfusion, revision arthroplasty, and knee arthroplasty; body mass index; and use of angiotensin-converting enzyme inhibitors. Diabetes, hypertension, duration of surgery, type of anesthesia, and preoperative serum creatinine were not found to be associated with renal injury. The key limitation was the availability of small number of studies. More longitudinal observational studies addressing the issue are the need of the hour, and, till then, a preventive strategy aimed at the identified risk factors should help.

Aims and Objectives: Total quality management is an essential component of laboratory to maintain quality and includes pre-analytical, analytical and post-analytical phases. Pre-analytical phase starts from ordering investigation by the clinician till it is analysed in the laboratory. It is essential that a pathologist is aware of the confounding factors that may lead to pre-analytical errors with the knowledge of reducing them to improve the quality of the lab. The present study was conducted to evaluate the pre-analytical errors in the haematology laboratory and steps taken to minimise it. Materials and Methods: The study was conducted in the Haematology Laboratory of Pathology Department, All India Institute of Medical Sciences, Rishikesh, over a period of 4 years and included all the blood samples analysed in the lab. The pre-analytical variables including requisition form, patient preparation, labelling, sample collection, quality and transportation were analysed for the errors along with the corrective actions taken to minimise them. Results: A total of 25,15,583 investigations were received in the haematology laboratory over a period of 4 years. The total errors observed in the haematology lab in pre-analytical phase were 13,031 comprising 0.51% of total haematological investigations during the study period. The most common error observed was due to clotted sample (40.3%), followed by haemolysed samples (15%) and incomplete or wrongly filled requisition forms (10%). Conclusion: Pre-analytical phase forms an integral part of total quality management system and its analysis is essential to minimise the errors in haematology lab. The quality of blood sample with completely filled requisition forms and prompt transportation of sample to the lab are essential components to avoid pre-analytical errors. In addition, continuous training and acknowledgement of non-conformance with root cause analysis is the basic key for reducing errors and improving quality of haematology lab.

Interstitial mycosis fungoides is a rare histopathologic variant of mycosis fungoides that may resemble interstitial granuloma annulare, inflammatory morphea, and interstitial granulomatous dermatitis. Reported is a case of a 62-year-old African American female who presented with an asymptomatic, progressive rash of the left underarm and abdomen with histologic features suggestive of granuloma annulare. Biopsies revealed an interstitial pattern of cells in the dermis with prominent small aggregates of atypical lymphocytes, a few atypical lymphocytes in the lower epidermis, and a mild increase in dermal mucin. Immunohistochemistry staining revealed the atypical lymphocytes to be positive for CD3 and CD8 and negative for CD4 and CD7, an aberrant immunoprofile. Mixed in the dermis with the atypical lymphoid cells were a few CD68 positive histiocytes and S100 protein positive dermal dendritic cells. T-cell receptor beta gene rearrangement studies showed nearly the same clonal peaks for TCRB rearrangement in two biopsy specimens from separate sites, all supporting a diagnosis of interstitial mycosis fungoides. The patient is undergoing treatment with full body narrowband UVB (nbUVB) phototherapy with notable improvement in skin discoloration and resolution of several abdominal lesions. A diagnosis of interstitial mycosis fungoides is challenging to make based on clinical features alone and is often clinically misdiagnosed. Awareness of histopathologic features is critical to make an accurate diagnosis and thus patient management.

Category: Midfoot/Forefoot Introduction/Purpose: Jones fracture is the fracture of the base of 5th metatarsal and is a commonly encountered in the clinical setting. Its management has always been a subject of great debate with paucity of consensus on post- operative weight bearing protocols. We aim to evaluate the efficacy of early weight bearing in the post-operative management of Jones fracture and assess its association with radiological union and patient reported outcomes. Methods: Retrospectively, patients undergoing fixation of Jones fracture from January 2011 to December 2020 were identified. Radiographic follow-up of at least 8 weeks was required for inclusion yielding 40 patients. Patients were grouped by early weight bearing (EWB) as tolerated (26 patients) and non-weight bearing (NWB) for 2 weeks followed by partial weight bearing (14 patients). Medical records were reviewed for demographic variables, associated comorbidities, type of surgical construct used, fracture type, mode of injury and union. Delayed union was defined as patients without radiographic evidence of union at 12.5 weeks. Patients completed PROMIS physical function, PROMIS pain interference, and FFI scoring postoperatively. Results: The mean age was 42.83+- 17.03 years with a female gender predominance (n=23; 57.5%) and an average BMI of 32.2 +- 8.7. Thirteen (50%) in the EWB and 5 (43%) in NWB groups experienced delayed radiological union (>12 weeks) and this did not differ by group. There was one nonunion in the NWB group and none in the EWB group. The number of wound complications did not vary by group. Seventeen patients completed postoperative FFI and PROMIS scores at a median of 40 months (41.5 IQR). The FFI and PROMIS scores did not differ by group. In the EWB group, the median PROMIS scores were physical function 43.7 (6.7 (IQR)) and pain interference 52.8 (10.1) compared to physical function 44.0 (11.6) and pain interference 55.2 (11.8) in the NWB group. The median total FFI score in the EWB group was 20.0 (27) compared to 32 (32) in the NWB group. Conclusion: The EWB group exhibited comparable results to the NWB group after surgical fixation of Jones fracture. Importantly, PROMIS scores indicate both groups had comparable functional outcomes at long term follow up and were within a standard deviation of the general population of the United States (Score of 50 with SD of 10) for both pain and function. While further investigation is required, EWB may have equivocal results in terms of union, wound complications, and functional outcomes while allowing for early mobilization after Jones fracture fixation.

The study presents the morpho-physiological performance under induced drought condition and molecular marker based genetic variability amongst 13 rice varieties released for cultivation in Uttar Pradesh, India. An attempt was made to identify suitable genotypes for drought affected areas, based on their morpho-physiological characteristics and genetic diversity. The physiological parameters of photosynthesis rate (A), transpiration rate (E), water use efficiency (WUE), along with the yield parameters and genetic diversity by simple sequence repeats marker (SSR) profile were analysed. The rice varieties PR-115 and PR-113 exhibited high water use efficiency, suggesting its possible advantageous response to drought due to low transpiration and high rate of net photosynthesis. The varieties, PR-115 and PR-113 were also found to be best performer in terms of yield under drought conditions. However, the more widely cultivated varieties namely Basmati, IR-36 and IR-20 were found to be intermediate in their response to drought for both yield and physiological parameters. The 19 simple sequence repeats marker (SSR) produces a total of 64 alleles across the 13 varieties, with alleles ranging from 2 to 7 per locus (average 3 alleles). The Polymorphic information content (PIC) value ranged from 0.13 to 0.78 with an average of 0.45 ± 0.19.

Accumulating evidence suggests the critical role of miR-590–5p in various aspects of cellular homeostasis, including cancer. Furthermore, we and others have recently demonstrated that miRNA-590–5p acts as an oncogene in some cancers while it acts as a tumor-suppressor in others. However, the role of miR-590–5p in oncogenesis is more complex, like a double-edged sword. Thus, this systematic review introduces the concept, mechanism, and biological function of miR-590–5p to resolve this apparent paradox. We have also described the involvement of miR-590–5p in crucial cancer-hallmarks processes like proliferation, invasion, metastasis, and chemo radioresistance. Finally, we have presented the possible genes/pathways targets of miR-590–5p through bioinformatics analysis. This review may help in designing better biomarkers and therapeutic targets for cancers.

Otosclerosis (OTSC) is the primary form of conductive hearing loss characterized by abnormal bone remodelling within the otic capsule of the human middle ear. A genetic association of the RELN SNP rs3914132 with OTSC has been identified in European population. Previously, we showed a trend towards association of this polymorphism with OTSC and identified a rare variant rs74503667 in a familial case. Here, we genotyped these variants in an Indian cohort composed of 254 OTSC cases and 262 controls. We detected a significant association of rs3914132 with OTSC (OR = 0.569, 95%CI = 0.386–0.838, p = 0.0041). To confirm this finding, we completed a meta-analysis which revealed a significant association of the rs3914132 polymorphism with OTSC (Z = 6.707, p

Background: There are an estimated 55 million internally displaced persons (IDPs) globally. IDPs commonly have worse health outcomes than host populations and other forcibly displaced populations such as refugees. Official development assistance (ODA) is a major source of the global financial response for health in low- and middle-income countries (LMICs), including for populations affected by armed conflict and forced displacement. Analysis of ODA supports efforts to improve donor accountability, transparency and the equitable use of ODA. The aim of this study is to examine international donor support and responsiveness to IDP health needs through analysis of ODA disbursements to LMICs between 2010 and 2019. Methods: ODA disbursement data to LMICs from 2010 to 2019 were extracted from the Creditor Reporting System (CRS) database and analysed with Stata software using a combination of: (i) text searching for IDP and refugee related terms; and (ii) relevant health and humanitarian CRS purpose codes. Descriptive analysis was used to examine patterns of ODA disbursement, and nonlinear least squared regression analysis was used to examine responsiveness of ODA disbursement to recipient country IDP population size and health system capacity and health characteristics. Findings: The study highlighted declining per IDP capita health ODA from USD 5.34 in 2010 to USD 3.72 in 2019 (with annual average decline of -38% from the 2010 baseline). In contrast, health ODA for refugees in LMICs increased from USD 18.55 in 2010 to USD 23.31 in 2019 (with an annual average increase of +14%). Certain health topics for IDPs received very low ODA, with only 0.44% of IDP health ODA disbursed for non-communicable diseases (including mental health). There was also weak evidence of IDP health ODA being related to recipient country IDP population size, and health system capacity and health characteristics. The paper highlights the need for increased investment by donors in IDP health ODA and to ensure that it is responsive to their health needs.

BACKGROUND: Menopause in females is a corporeal stage that gives rise to a number of adaptive changes both at systemic and oral levels, prototypically occurring in the late fourth or fifth decade of life. Though physiological aging affects the oral tissue, the hormonal changes due to menopause also act as a major contributing factor in deteriorating the health of oral tissues. Thus, the main aim of our study was to compare the overall periodontal status and alkaline phosphatase levels in the saliva of females in their pre and postmenopausal ages. MATERIAL AND METHODS: This study was conducted on 200 female subjects coming to the Department of Periodontology at Rajendra Institute of Medical Science for oral prophylaxis. The subjects were arbitrarily selected in the age group ranging from 15 to 70 years and were further divided based on the inclusion criteria. Group A included 100 subjects with age ranging from 15 to 45 years, and group B, 100 subjects with age 54 to 70 years. Signs of periodontitis including clinical attachment loss, furcation involvement, and probing depth and salivary alkaline levels were obtained, evaluated, compared, and analyzed. RESULTS: In group A 65% of patients had grade 0 and 28% had grade 1 of clinical attachment level. Similarly in group B, 44% of the total had grade 0 of clinical attachment loss, 38% had grade 1, and 18% were of grade 2. On evaluating grades of furcation involvement, around 45% of the total patients in group A were grade 1 (incipient, pocket formation), while in group B, 51% of the total patients were grade 1. At least 46% in group A and only 20% in group B had no signs of furcation involvement. Salivary alkaline phosphatase levels in pre and postmenopausal patients showed a significant difference between the two groups was obtained. CONCLUSION: The study concluded a major difference in the periodontal health of pre and postmenopausal women with many influencing factors apart from menopause itself.

Abstract Background Coleoptera is the second most important group of entomofauna associated with decomposition, yet little is known about its role in decomposition and postmortem colonization of carcasses in India and other parts of the world. Consequently, a preliminary study was conducted to study the succession of forensically important Coleoptera using goat carrion as an animal model. Results Five decomposition stages were observed during the experiment. A total of 1174 adult coleopterans belonging to 21 species and seven families were collected during this study. Throughout faunal succession, Histeridae and Silphidae were the dominant Coleopteran families, and they occurred mainly during the bloated and decay stages of decomposition; Necrophila (Calosilpha) ioptera was the dominant species present from the bloated to dry stage of putrescence. Two species, Pachylister bellicus and Saprinus sternifossa were reported for the first time from India. Conclusion This study provides baseline data regarding Coleopteran species associated with different decomposition stages, but more extensive studies need to be performed to develop a geographical database on arthropod succession from as many habitats as possible so that this kind of data can be used in forensic cases.

Various pollutants are being introduced into aquatic ecosystems both directly or indirectly as a result of industrialisation and urbanisation. Heavy metal contamination in freshwater bodies is of great concern owing to their toxicity, persistence and bioaccumulation. In toxicology, behavioural bioassays are used as a tool to assess heavy metal toxicity. Even at very low doses, chemicals can cause organisms to exhibit rapid behavioural responses. The current study deals with the acute toxicity of cadmium, zinc and their mixture to freshwater fish, Labeo rohita. Static bioassay tests were carried out to evaluate LC50 value of Cadmium (Cd), Zinc (Zn) and a mixture of both metals (Cd+Zn) for freshwater fish, L. rohita as well as the behavioural responses were also observed. Fishes were treated with various concentrations of metals for different exposure periods and per cent mortality was recorded. The objective of this study was to grasp the link between mortality and abnormal behavioural alterations of L. rohita exposed to CdCl2, ZnCl2 and a mixture of both metals (CdCl2+ ZnCl2). The major behavioural responses observed during the experiment were restlessness, jumping, erratic swimming, gulping of air at the surface, loss of equilibrium, sluggishness, opercular movements and fishes lying on the water surface before death etc. were observed in exposed fishes. The observed data showed that L. rohita can be used as a good bio-indicator for heavy metal contamination in freshwater bodies. Thus, a behavioural bioassay is more promising than lethality evaluating bioassays, which are currently employed for toxicant risk evaluation

BIN1 (amphyphysin-II) is a structural protein involved in T-tubule (TT) formation and phosphatidylinositol-4,5-bisphosphate (PIP2) is responsible for localization of BIN1 to sarcolemma. The goal of this study was to determine if PIP2-mediated targeting of BIN1 to sarcolemma is compromised during the development of heart failure (HF) and is responsible for TT remodeling. Immunohistochemistry showed co-localization of BIN1, Cav1.2, PIP2, and phospholipase-Cβ1 (PLCβ1) in TTs in normal rat and human ventricular myocytes. PIP2 levels were reduced in spontaneously hypertensive rats during HF progression compared to age-matched controls. A PIP Strip assay of two native mouse cardiac-specific isoforms of BIN1 including the longest (cardiac BIN1 #4) and shortest (cardiac BIN1 #1) isoforms as well human skeletal BIN1 showed that all bound PIP2. In addition, overexpression of all three BIN1 isoforms caused tubule formation in HL-1 cells. A triple-lysine motif in a short loop segment between two helices was mutated and replaced by negative charges which abolished tubule formation, suggesting a possible location for PIP2 interaction aside from known consensus binding sites. Pharmacological PIP2 depletion in rat ventricular myocytes caused TT loss and was associated with changes in Ca2+ release typically found in myocytes during HF, including a higher variability in release along the cell length and a slowing in rise time, time to peak, and decay time in treated myocytes. These results demonstrate that depletion of PIP2 can lead to TT disruption and suggest that PIP2 interaction with cardiac BIN1 is required for TT maintenance and function.

Objective Large data on the clinical characteristics and outcome of COVID-19 in the Indian population are scarce. We analysed the factors associated with mortality in a cohort of moderately and severely ill patients with COVID-19 enrolled in a randomised trial on convalescent plasma.Design Secondary analysis of data from a Phase II, Open Label, Randomized Controlled Trial to Assess the Safety and Efficacy of Convalescent Plasma to Limit COVID-19 Associated Complications in Moderate Disease.Setting 39 public and private hospitals across India during the study period from 22 April to 14 July 2020.Participants Of the 464 patients recruited, two were lost to follow-up, nine withdrew consent and two patients did not receive the intervention after randomisation. The cohort of 451 participants with known outcome at 28 days was analysed.Primary outcome measure Factors associated with all-cause mortality at 28 days after enrolment.Results The mean (SD) age was 51±12.4 years; 76.7% were males. Admission Sequential Organ Failure Assessment score was 2.4±1.1. Non-invasive ventilation, invasive ventilation and vasopressor therapy were required in 98.9%, 8.4% and 4.0%, respectively. The 28-day mortality was 14.4%. Median time from symptom onset to hospital admission was similar in survivors (4 days; IQR 3–7) and non-survivors (4 days; IQR 3–6). Patients with two or more comorbidities had 2.25 (95% CI 1.18 to 4.29, p=0.014) times risk of death. When compared with survivors, admission interleukin-6 levels were higher (p10 (9.97, 3.65–27.13, p1.0 mg/L (2.50, 1.14–5.48, p=0.022), ferritin ≥500 ng/mL (2.67, 1.44–4.96, p=0.002) and lactate dehydrogenase ≥450 IU/L (2.96, 1.60–5.45, p=0.001) were significantly associated with death.Conclusion In this cohort of moderately and severely ill patients with COVID-19, severity of illness, underlying comorbidities and elevated levels of inflammatory markers were significantly associated with death.Trial registration number CTRI/2020/04/024775.

Background: Student psychological health has been an increasing concern. The COVID-19 pandemic situation has brought this vulnerable population into renewed focus. Objective: Our study aims to conduct a timely assessment of the effects of the COVID-19 pandemic on the mental health of college graduates and postgraduates. Methodology: We conducted online survey with 550 students to understand the effects of the pandemic on their psychology and well-being. The data were analyzed through quantitative and qualitative methods. Results: Of the 550 students, 138 (71%) indicated increased stress and anxiety due to the COVID-19 outbreak. When asked about how the lockdown in COVID-19 situation affecting them, 97% said that it is severely affecting them. When asked about what the problems do you faced during online class, 5% said the Internet, 83.8% said noninteractive, and 11.2% said lack of explanatory mediums. When asked about number of hours spent on the Internet, 100% said more than 10 h. When asked about the activities to keep yourself busy during lockdown in COVID-19 situation, 37% said social media followed by 23% who mentioned cooking. Conclusion: Due to the long-lasting pandemic situation and onerous measures such as lockdown and stay-at-home orders, the COVID-19 pandemic brings negative impacts on education. The findings of our study highlight the urgent need to develop interventions and preventive strategies to address the psychological health of college students.

Background: COVID-19 pandemic resulted in lockdown affecting all businesses globally. Everyone was forced to work from home (WFH) leading to challenges in productivity and motivation. Methodology: One thousand working professionals who worked from home participated in the online survey with semi-structured questionnaire using nonprobability Snowball sampling technique. Descriptive statistics was used to analyze the findings and to collect data method. Results: Participants were asked about their biggest worries during lockdown COVID-19 situation and their biggest worry was infection to COVID-19/death. Professionals were asked whether they were affected or not affected due to “WFH” in COVID situation. The questionnaire items were clubbed into six major categories of job role overload, lifestyle choices, family distraction, occupational discomfort, job performance, and distress, and majority categories were affected. Conclusion: Thus, it is observed that the increase in work commitments leads to distress among employees while distractions from family members disrupt the quality of work. While good job performance contributes to life satisfaction, distress significantly diminished it. This paves the way for more studies to be done on work–life balance under WFH arrangements for as long as the pandemic of COVID-19 is prevalent.

Background: Many academic institutions have been cheering lecturers to execute flipped learning methodologies. The present study determined perceived competency of dental interns toward dental practice among various dental colleges. Materials and Methods: A total of 138 interns of dental college were provided with self-administered questionnaire with close-ended questions. All were instructed to read it and submit it. Results: Out of 138 subjects, there were 78 males and 60 females. The mean value for general patient management was 3.12 and 3.0 in males and females, periodontology and dental public health was 2.54 and 2.65, conservative dentistry was 2.70 and 2.82, oral rehabilitation was 2.32 and 2.30, orthodontics was 2.10 and 2.28, management of children and special needs patients was 2.52 and 2.64, oral and maxillofacial surgery was 2.49 and 2.42, and drug and emergency management was 2.62 and 2.60, respectively. Conclusion: Dental interns were well prepared toward dental practice.

The use of smartphone-based applications as a telenutrition tool could redefine the nutritional management of IBD. We developed and validated a digital health platform in the form of a smartphone application for the nutritional assessment of IBD patients. Our team of gastroenterologists and dieticians at the All-India Institute of Medical Sciences, New Delhi developed a smartphone application titled IBD NutriCare, which was made available in both Android and iOS interfaces in English and seven other Indian languages. The application includes >650 Indian recipes and provides subjective global assessment and IBD clinical activity scores in a patient-friendly manner. The utility of the smartphone app was validated in comparison with the traditional 24-h dietary recall method. A total of 49 IBD patients were enrolled in the study. The mean difference in energy intake between the two dietary assessment methods was −4.776 kJ (95% LOA, range −417.916–408.365 kJ). A total of 94% of patients found the smartphone application convenient and acceptable in comparison to the recall method for dietary assessment. Bland–Altman plots showed a good level of agreement for nutrients and food groups between the two methods. Telenutrition in the form of a smartphone application helps in real-time tracking of dietary details of IBD patients, thus making appropriate interventions and large-scale data acquisition feasible.

Background: In this study, a novel electromechanical robotic exoskeleton was developed for the rehabilitation of distal joints. The objective was to explore the functional MRI and the neurophysiological changes in cortical-excitability in response to exoskeleton training for a 9-year chronic stroke patient.Case-Report: The study involved a 52-year old female patient with a 9-year chronic stroke of the right hemisphere, who underwent 20 therapy sessions of 45 min each. Cortical-excitability and clinical-scales: Fugl-Mayer (FM), Modified Ashworth Scale (MAS), Brunnstrom-Stage (BS), Barthel-Index (BI), Range of Motion (ROM), were assessed pre-and post-therapy to quantitatively assess the motor recovery.Clinical Rehabilitation Impact: Increase in FM wrist/hand by 6, BI by 10, and decrease in MAS by 1 were reported. Ipsilesional Motor Evoked Potential (MEP) (obtained using Transcranial Magnetic Stimulation) was increased by 98 μV with a decrease in RMT by 6% and contralesional MEP was increased by 43 μV with a decrease in RMT by 4%. Laterality Index of Sensorimotor Cortex (SMC) reduced in precentral- gyrus (from 0.152 to −0.707) and in postcentral-gyrus (from 0.203 to −0.632).Conclusion: The novel exoskeleton-based training showed improved motor outcomes, cortical excitability, and neuronal activation. The research encourages the further investigation of the potential of exoskeleton training.

This study focuses on the estimation of population variance of study variable in stratified random sampling using auxiliary information when the observations are contaminated by measurement errors. Three classes of estimators of variance under measurement error are proposed by using the approach of Srivastava and Jhajj [18] for the study variable. The properties of the estimator viz. bias and mean square error of the proposed classes of estimators are provided. The conditions for which proposed estimators are more efficient compared to usual estimators are discussed. It is shown that the proposed classes of estimators include a large number of estimators of the population variance of stratified random sampling and their bias and mean square error can be easily derived.

Introduction: Craniovertebral junction is the “zone of transition” between the skull and cervical spine so its detailed discussion is lacking in so many standard textbooks addressing these regions. These anomalies are especially common in the Indian subcontinent. Accurate diagnosis, probable aetiology and pre-treatment evaluation considerably affect the prognosis of patients. The aim of this study was to classify various Craniovertebral junction disorders according to their aetiology and to correlate the imaging findings with the clinical profile of the patients and histopathology whenever possible. Methods: This prospective observational study was done in our department over the period of one year from August 2016 to July 2017. 57 North Indian patients from all age groups and both sex, who had imaging features suggesting craniovertebral junction pathology were selected for the study. Results: Our study group comprised 34 males and 23 females with a male to female ratio of 1.47: 1. The most common age group was 11-20 years and the most common aetiology being developmental followed by infective, autoimmune and inflammatory disorders. Conclusions: CVJ abnormalities are a group of treatable neurological disorders, and are approached with much caution by clinicians. Thus, it is crucial that radiologists should be able to make a precise diagnosis, categorize them into etiological groups, and give precise anatomical information on MDCT and/or MRI, as this information ultimately helps determine the management of such abnormalities and their prognosis.

Abstract Background Plant roots contribute significant amount of nitric oxide (NO) in the rhizosphere as a component of NO in the ecosystem. Various pharmacological investigations on NO research in plants seek to quench endogenous NO by using externally applied NO quenchers, mainly 2-phenyl-4,4,5,5,-tetramethylimidazoline-1-oxyl 3-oxide (PTIO) and its more soluble form-carboxy-PTIO (cPTIO). Owing to serious limitations in its application cPTIO is no more a desired compound for such applications. Result Present work highlights the significance of using hemoglobin in the bathing solution to not only release endogenous NO from plant tissue but also to quench it in a concentration-dependent manner. Conclusion The protocol further demonstrates the diffusibility of NO from intracellular locations in presence of externally provided hemoglobin. The proposed method can have widespread applications as a substitute to debatable and currently used cPTIO as a NO scavenger.

Purpose: A pilot randomized control trial to compare the efficacy and side effects of intralesional and oral propranolol in periorbital and eyelid capillary hemangiomas. Methods: Twenty patients were prospectively randomized to two groups of ten each. Group 1 was initiated on oral propranolol 1 mg/kg/day titrated to final dose of 3 mg/kg/day over 1 week which was continued for 6 months and then tapered over 1 week; Group 2 received 3 doses of direct intralesional propranolol hydrochloride 1 mg/ml; 0.2 ml/cm 4–6 weeks apart. Hemangioma area and corneal astigmatism were measured. Results: Within each group at 6 months there was a significant reduction in area (group 1: 83.48 ± 11.67%,P= 0.0019; group 2: 67.78 ± 21.71%,P= 0.0019) and improvement in astigmatism (pre, post: group 1: 2.98D @ 179.8°, 1.13D @ 179.8°,P= 0.0045; group 2: 1.62D @ 90.16°, 0.75D @ 179.9°,P= 0.0001). There was no difference in area reduction (P = 0.056), change in appearance (P = 0.085), ptosis (P = 0.23) and side effects (lethargy, poor feeding;P= 0.171) between the two groups. Conclusion: Efficacy and side effects with intralesional propranolol are comparable to oral propranolol for periorbital and eyelid lesions.

Background: The surge of the geriatric population has led to design research studies related to health problems in this age group worldwide. Bone marrow examination which is an important diagnostic tool for various diseases may vary in geriatric population in comparison to younger groups. The present study was, therefore, conducted to study the indications and morphological features of bone marrow examination in geriatric population in north Himalayan region of India. It was also intended to study if there is any variation in these findings from elderly populations in other parts of the world. Material and Methods: Study was conducted in an institute situated in north Himalayan Uttarakhand state of India over a period of two years including patients above 60 years of age who underwent bone marrow examination. Results: Total 156 cases underwent bone marrow examination with most common indication being suspicion of lymphoma (18.5%) followed by cytopenia (17.3%). Nutritional anaemia was most common pathological diagnosis in 16.6% cases. Diagnostic discordance between aspirate and biopsy was observed in 5.7% of total cases with non-Hodgkin's lymphoma (NHL) being the most common misdiagnosis on aspirate. Conclusion: Nutritional anaemia particularly iron deficiency anaemia is the most common diagnosis of bone marrow examination indicating the importance of nutritional therapy in the elderly population of this region. Bone marrow biopsy proves to be an important adjunct to aspiration in precise diagnosis with minimal complications. The awareness of bone marrow findings would not only be helpful to clinicians and pathologists but also provide valuable information to the policymakers to improve the quality of health in the geriatric population of this area.

Light chain myeloma (LCM) has a reported worldwide incidence of approximately 15%–20% among all multiple myeloma (MM) patients. Few western studies have shown strong correlation of LCM with anemia, higher International Staging System scores, proclivity to renal failure, elevated lactate dehydrogenase levels, raised serum-free light chain ratio, higher frequency of extramedullary plasmacytomas, and poorer overall survival, attributable probably to lack of differentiation and skeletal destruction. The primary aim of this retrospective observational study was to define the clinical and hematological characteristics as well as prognostic outcome of Indian LCM patients in comparison with the IgG and IgA subtypes. Patients were defined according to the International Myeloma Working Group diagnostic criteria 2016 and staged as per the International Staging System. Out of 104 patients of newly diagnosed MM in which results of serum immunofixation (IFE) were available, 65 were of IgG isotype (62.5%), 15 had IgA (14.4%), and 24 had light chain myelomas (LCMs) (23.1%). It was observed that LCM patients significantly correlated with hypercalcemia and higher serum-free light chain ratios, whereas IgA patients were strongly associated with anemia and lower serum albumin levels. However, no difference was found among the three subgroups in terms of serum lactate dehydrogenase levels, proclivity to renal failure, presence of lytic bone lesions, prognostic scoring, pretransplant chemosensitivity, and progession-free survival (1 year). Thus, it may be concluded that Indian LCM patients have significantly different clinico-hematological profile in comparison with other published studies worldwide. Also, their prognostic outcomes are not worse when compared with patients of other protein isotypes, probably due to standardized treatment regimens applied.

Background: Pancytopenia, an important hematological presentation is associated with different causes, which may vary in different regions. Uttarakhand, a north Himalayan state of India lacks studies of pancytopenia and the prevalent causes present in this region. Therefore, the present study was conducted to study the clinico-hematological profile of pancytopenia in a tertiary care center in the Uttarakhand, a north Himalayan state of India. It was also intended to study if these causes showed any variation from other studies done in different regions of India. Materials and Methods: The present observational study was conducted in a tertiary care institute situated in Uttarakhand state of India over a period of 1 year and 8 month from June 2017 to Feb 2019 including all the cases of pancytopenia. Results: The most common cause of pancytopenia was megaloblastic anemia (25%), followed by aleukemic leukemia and hypoplastic/aplastic anemia (19.1% each). Visceral leishmaniasis also constituted an important cause of pancytopenia in this study (11.7%). Conclusion: The study concludes that megaloblastic anemia and aleukemic leukemia are the most common cause of pancytopenia. Although leishmaniasis is considered to be non-endemic in this region, it constitutes an important cause of pancytopenia here. The clinicians, especially the physicians practicing the primary care and pathologists, should be aware of the different causes of pancytopenia present in this Himalayan region of India; therefore, delay in diagnosis can be prevented along with unnecessary investigations.

Adult mammalian hearts have a very limited regeneration capacity, due largely to a lack of cardiomyocyte (CM) proliferation. It was recently reported that epicardial, but not myocardial, follistatin-like 1 (Fstl1) activates CM proliferation and cardiac regeneration after myocardial infarction (MI). Furthermore, bacterially synthesized human FSTL 1 (hFSTL1) was found to induce CM proliferation, whereas hFSTL1 synthesized in mammals did not, suggesting that post-translational modifications (e.g., glycosylation) of the hFSTL1 protein affect its regenerative activity. We used modified mRNA (modRNA) technology to investigate the possible role of specific hFSTL1 N-glycosylation sites in the induction, by hFSTL1, of CM proliferation and cardiac regeneration. We found that the mutation of a single site (N180Q) was sufficient and necessary to increase the proliferation of rat neonatal and mouse adult CMs in vitro and after MI in vivo, respectively. A single administration of the modRNA construct encoding the N180Q mutant significantly increased cardiac function, decreased scar size, and increased capillary density 28 days post-MI. Overall, our data suggest that the delivery of N180Q hFSTL1 modRNA to the myocardium can mimic the beneficial effect of epicardial hFSTL1, triggering marked CM proliferation and cardiac regeneration in a mouse MI model. Keywords: cardiomyocytes proilferation, cardiac regeneration, gene therapy

Abstract Heart failure (HF) remains a major cause of morbidity and mortality worldwide. One of the risk factors for HF is cardiac hypertrophy (CH), which is frequently accompanied by cardiac fibrosis (CF). CH and CF are controlled by master regulators mTORC1 and TGF‐β, respectively. Type‐2‐phosphatidylinositol‐5‐phosphate‐4‐kinase‐gamma (Pip4k2c) is a known mTORC1 regulator. It is shown that Pip4k2c is significantly downregulated in the hearts of CH and HF patients as compared to non‐injured hearts. The role of Pip4k2c in the heart during development and disease is unknown. It is shown that deleting Pip4k2c does not affect normal embryonic cardiac development; however, three weeks after TAC, adult Pip4k2c−/− mice has higher rates of CH, CF, and sudden death than wild‐type mice. In a gain‐of‐function study using a TAC mouse model, Pip4k2c is transiently upregulated using a modified mRNA (modRNA) gene delivery platform, which significantly improve heart function, reverse CH and CF, and lead to increased survival. Mechanistically, it is shown that Pip4k2c inhibits TGFβ1 via its N‐terminal motif, Pip5k1α, phospho‐AKT 1/2/3, and phospho‐Smad3. In sum, loss‐and‐gain‐of‐function studies in a TAC mouse model are used to identify Pip4k2c as a potential therapeutic target for CF, CH, and HF, for which modRNA is a highly translatable gene therapy approach.

Advanced LIGO and Advanced Virgo are monitoring the sky and collecting gravitational-wave strain data with sufficient sensitivity to detect signals routinely. In this paper we describe the data recorded by these instruments during their first and second observing runs. The main data products are gravitational-wave strain time series sampled at 16384 Hz. The datasets that include this strain measurement can be freely accessed through the Gravitational Wave Open Science Center at http://gw-openscience.org, together with data-quality information essential for the analysis of LIGO and Virgo data, documentation, tutorials, and supporting software.

Heavy metal contamination in fresh water bodies is of great concern owing to their toxicity, persistence and bioaccumulation. The current study deals with the acute toxicity of cadmium to fresh water fish, Channa punctatus. The objective of this study was to grasp the link between mortality and abnormal behavioral and morphological changes of C. punctatus exposed to cadmium chloride. Static bioassay tests were carried out to evaluate LC50 value of Cadmium (Cd) for fresh water fish, C. punctatus as well as the behavioral responses and morphological changes were also observed. Fish after treatment with various concentrations of cadmium chloride for different exposure period the percent mortality was recorded. The lowest cadmium chloride concentration at which mortality was observed as 45 mg/l. The first death of experimental fish was recorded as 125 mg/l at 24 hrs. of exposure. After 96 hrs. LC50 value of cadmium (Cd) was found to be 80.62mg/l. The major behavioral responses observed during the experiment were restlessness, jumping, erratic swimming, gulping of air at the surface, loss of equilibrium, sluggishness,opercular movements and fishes lied on the water surface before death and morphological changes like, discoloration of skin, pigmented patches on body, shedding of scales, sedimentation of chemical on body, mucous secretion, and ballooning were observed in exposed animals. The observed data showed that C.punctatus can be used as a good bio-indicator for heavy metal contamination in fresh water bodies.

The foremost concern in forensic entomology is the explicit identification of the species recovered from the crime scene. From the different orders of insects, Diptera is the prime focus in this field, followed by Coleoptera, whose identification can be extremely helpful for corpses in later decomposition stages. In this study, cytochrome oxidase subunit II (COII) was used to check its adequacy as a genetic marker and to create a reference database for eleven species belonging to five families of Coleoptera, namely, Silphidae, Staphylinidae, Histeridae, Dermestidae and Scarabaeidae, from two different states in India to assist in the accurate identification of imperative beetle species in medico-legal entomology. To achieve this, standard protocols of DNA isolation, amplification and sequencing were followed. We concluded that the COII gene can be used as a molecular marker for the identification of forensically relevant species, as observed from the similarities between the phylogenetic relationship constructed by COII and morphological data.

Coronavirus disease 2019 (COVID-19), caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus, has emerged as a global pandemic worldwide. In this study, we used ARTIC primers–based amplicon sequencing to profile 225 SARS-CoV-2 genomes from India. Phylogenetic analysis of 202 high-quality assemblies identified the presence of all the five reported clades 19A, 19B, 20A, 20B, and 20C in the population. The analyses revealed Europe and Southeast Asia as two major routes for introduction of the disease in India followed by local transmission. Interestingly, the19B clade was found to be more prevalent in our sequenced genomes (17%) compared to other genomes reported so far from India. Haplotype network analysis showed evolution of 19A and 19B clades in parallel from predominantly Gujarat state in India, suggesting it to be one of the major routes of disease transmission in India during the months of March and April, whereas 20B and 20C appeared to evolve from 20A. At the same time, 20A and 20B clades depicted prevalence of four common mutations 241 C > T in 5′ UTR, P4715L, F942F along with D614G in the Spike protein. D614G mutation has been reported to increase virus shedding and infectivity. Our molecular modeling and docking analysis identified that D614G mutation resulted in enhanced affinity of Spike S1–S2 hinge region with TMPRSS2 protease, possibly the reason for increased shedding of S1 domain in G614 as compared to D614. Moreover, we also observed an increased concordance of G614 mutation with the viral load, as evident from decreased Ct value of Spike and the ORF1ab gene.

Background: Low back pain (LBP) is a frequent cause of global disability and activity limitation. In the majority of cases, LBP is nonspecific, yet diagnostic confirmation is required to rule out serious underlying pathologies such as infection, tumour, fracture or degenerative disease. It can be done by a number of imaging techniques. Of all available techniques, MRI is currently the imaging modality of choice owing to lack of radiation, multiplanar reformation capabilities and high contrast resolution. Objectives: To determine various MRI patterns and the common sites of spinal degenerative lesions among patients with LBP. Method: This study was conducted on 622 patients suffering from non-traumatic LBP, referred for MRI of the lumbar spine. MRI database of the study population were analysed using axial T2-weighted, sagittal STIR, T1and T2-weighted and coronal STIR images. After excluding patients with h/o prior surgery and MR findings suggesting infective or neoplastic etiologies, 598 patients constituted the sample size of our study. Results: A review of 598 patients with LBP revealed that degenerative changes in intervertebral disc were the most common abnormality detected. Among these, Disc bulge was the most common abnormality followed by disc desiccation, protrusion, extrusion, HIZ/annular tear, reduced IVD space and Schmorl’s nodes. Other non- disc degenerative findings were Modic endplate changes, facet joint arthropathy, osteophytes, Spinal canal stenosis and Ligamentum Flavum hypertrophy. Conclusions: Results reported the common occurrence of lumbar disc degenerative disease in patients with low backache. Research efforts should attempt to trim down risk factors and perk up the quality of life.