Swim exercise training and adaptations in the antioxidant defense system of myocardium of old rats: Relationship to swim intensity and duration

We examined a suitable swim program of different intensities and durations that could evoke changes in the myocardial antioxidant capacity in 22-month-old rats. Male rats (Rattus norvegicus) were assigned to either a sedentary control (SE-C) group or one of six trainee groups. Animals were swim-exercised for 4 weeks with either 20 min or 40 min/day, and three intensities, low, moderate and high. Low-intensity at 20 min/day elicited maximum swim velocity (S v) and endurance capacity (P<0.05). While serum total cholesterol, triglyceride and low-density lipoprotein (LDL-C) levels were significantly reduced, high-density lipoprotein (HDL-C) showed an increase (P<0.05) in low-intensity trained rats (20 min/day) over SE-C. Notable reduction in blood lactate was also evident. Exercise training significantly increased superoxide dismutase (Mn-SOD), decreased lipid peroxidation products, malondialdehyde and lipofuscin in the left and right ventricles. Increased Mn-SOD with concomitant decrease in lipofuscin in left ventricle was significantly greater than in right ventricle. Moderate- to high-intensity exercise was not effective in either reducing lipid peroxidation products or elevating Mn-SOD activity. These data suggest that swim training at low-intensity of 20 min/day is beneficial as a major protective adaptation against oxidative stress in old myocardium. © 2003 Elsevier Inc. All rights reserved

Clinical response to chemotherapy in non-small cell lung carcinoma patients

Background: Lung carcinoma is the most common. With this, a study was conducted to assess the clinical profile of Non-small cell lung carcinoma (NSCLC) and also to evaluate the response to chemotherapy in various stages of NSCLC.Methods: It was a prospective study. All the clinically confirmed cases with NSCLC were taken into consideration. Clinical staging was done, diagnosis was confirmed by histopathological findings. Treatment was given depending on the stage of carcinoma. Patients were evaluated before each cycle of chemotherapy for any progression of disease. Pathological response was evaluated after completion of 6 cycles of chemotherapy. Chi square test was used to find the statistical significance; p<0.05 was considered statistically significant.Results: Total 153 patients admitted to oncology wing were taken to the study, with mean age 59.07±10.618 years, 2.6 male female ratio. In this 73% were in stage III and the remaining in stage IV NSCLC. Majority (56.10%) of the study subjects in stage III NSCLC showed partial response, Majority (68%) of the subjects in stage IV NSCLC showed partial response; the difference was Statistically significant (p<0.05).Conclusions: NSCLS is common in older people with male dominance due to habits

Essential function for PDLIM2 in cell polarization in three-dimensional cultures by feedback regulation of the β1-Integrin–RhoA signaling axis

PDLIM2 is a cytoskeletal and nuclear PDZ-LIM domain protein that regulates the stability of Nuclear Factor kappa-B (NF kappa B) and other transcription factors, and is required for polarized cell migration. PDLIM2 expression is suppressed by methylation in different cancers, but is strongly expressed in invasive breast cancer cells that have undergone an Epithelial Mesenchymal Transition (EMT). PDLIM2 is also expressed in non-transformed breast myoepithelial MCF10A cells and here we asked whether it is important for maintaining the polarized, epithelial phenotype of these cells. Suppression of PDLIM2 in MCF10A cells was sufficient to disrupt cell polarization and acini formation with increased proliferation and reduced apoptosis in the luminal space compared to control acini with hollow lumina. Spheroids with suppressed PDLIM2 exhibited increased expression of cell-cell and cell-matrix adhesion proteins including beta 1 (beta 1) integrin. Interestingly, levels of the Insulin-like growth factor 1 receptor (IGF-1 R) and Receptor of activated protein kinase C 1 (RACK1), which scaffolds IGF-1R to beta 1 integrin, were also increased, indicating a transformed phenotype. Focal Adhesion Kinase (FAK) and cofilin phosphorylation, and RhoA Guanosine Triphosphatase (GTPase) activity were all enhanced in these spheroids compared to control acini. Importantly, inhibition of either FAK or Rho Kinase (ROCK) was sufficient to rescue the polarity defect. We conclude that PDLIM2 expression is essential for feedback regulation of the beta 1-integrin-RhoA signalling axis and integration of cellular microenvironment signals with gene expression to control the polarity of breast epithelial acini structures. This is a mechanism by which PDLIM2 could mediate tumour suppression in breast epithelium

Association studies of grain iron and zinc concentrations with yield and other agronomic traits using F2 populations of two crosses in sorghum (Sorghum bicolor L. Moench)

Micronutrient malnutrition affects more than one-half of the world’s population, especially women and pre-school children (Nestel et al., 2006). World Health Organization (WHO) of the United Nations estimated that mal nutrition is an underlying cause of 53% of all deaths in children under five years of age and recognized that the two micronutrients iron and zinc and pro-vitamin A (â-carotene) are limiting (Ma et al., 2008). Sorghum [Sorghum bicolour (L.) Moench], being the staple food and fodder crop in parts of semi-arid region of the world and the second cheapest source of energy (63.4 - 72.5 % starch) and micronutrients such as iron (Fe) and zinc (Zn) after pearl millet, if enriched with iron and zinc concentrations, can address the micronutrient requirements of the undernourished populations. Moreover, the poor and vulnerable groups in the society, particularly in India depend upon sorghum for their calorie and micronutrient requirement in the absence of access and affordability to nutrient-rich foods like vegetables, fruits and animal products. A study on association of grain iron and zinc concentrations with agronomic traits is needed to help the breeder in devising a suitable breeding strategy for the enhancement of micronutrient density in sorghum. Hence, this study was undertaken at ICRISAT, Patancheru with an aim to analyze the relationships of grain iron and zinc concentrations with grain yield and other agronomic traits in sorghum

Acinic Cell Carcinoma with Extensive Neuroendocrine Differentiation: A Diagnostic Challenge

Primary salivary gland carcinoma with neuroendocrine differentiation is of rare occurrence, especially so in the parotid gland. Amongst the various reported primary tumors with neuroendocrine differentiation, acinic cell carcinoma (ACC) one such tumor. A 48 year old lady presented with a gradually increasing right infra-auricular swelling for a period of 1 year which enlarged suddenly in a short period. Contrast Enhanced Computed Tomography (CECT) suggested diagnosis of Pleomorphic Adenoma. Fine Needle Aspiration Cytology (FANC) yielded a cystic fluid suggesting a possibility of Warthin’s tumor or Oncocytic lesion. Intraoperative findings were suggestive of a Warthin’s tumor. Initial histopathological examination of the tumor was suggestive of neuroendocrine carcinoma. However, extensive sectioning revealed peripheral islands of ACC. Immunoexpression of S-100, Neuron specific Enolase (NSE), Chromogranin A and Synaptophysin confirmed the diagnosis. The possibility of neuroendocrine differentiation in a primary salivary gland tumor should be kept in mind whenever a salivary gland tumor shows only neuroendocrine histology

Tube-assisted Minimally Invasive versus Open Posterior Decompression for Multilevel Degenerative Cervical Myelopathy: A Prospective Comparative Study

Objective There have been several reports of minimally invasive decompression for cervical canal stenosis and degenerative myelopathy. Most of these reports are for less than 4 levels and there have not been any comparative studies between Open and MIS cervical decompression for multilevel (≥4) degenerative cervical myelopathy. Methods Twenty consecutive patients were allotted to undergo either ‘Open’ cervical laminectomy (n=10) or MIS posterior cervical decompression (n=10). All patients were evaluated for 1. Clinical, (JOA, MDI, NDI, Nurick grade, Blood loss, Duration of surgery); 2. Radiological (CSA of dural sac and Spinal cord, Muscle edema on post-op T2W MRI); 3. Laboratory (TLC, CRP, ESR, CPK) and 4. Physical (Isometric neck extensor muscle strength). Differences between Open and MIS groups were calculated with respect to above parameters. Results The mean number of levels decompressed was 4.4 (range, 4–6). MIS group had significantly longer duration of surgery and lesser blood loss as compared to open group. The patients in open group were more disabled than MIS group pre-operatively, as evidenced by higher MDI and NDI. However, proportionate improvements were seen in both groups post-operatively in terms of all clinical parameters. Postoperative increase in CSA of spinal cord was also identical in both groups. Elevations in CRP and ESR were significantly higher in Open group post-operatively as compared to MIS group. Post-operative extensor neck muscle strength improved to a higher extent in MIS group as compared to open group though this was not statistically significant. No patient had any major post-operative complications. Conclusion MIS posterior cervical decompression is safe and effective, can achieve similar extent of decompression and degree of clinical improvement as compared to open surgery. MIS has definite advantages of lesser blood loss, reduced tissue injury and better improvement in post-operative neck muscle strength as compared to open surgery

Antimicrobial resistance among migrants in Europe: a systematic review and meta-analysis

BACKGROUND: Rates of antimicrobial resistance (AMR) are rising globally and there is concern that increased migration is contributing to the burden of antibiotic resistance in Europe. However, the effect of migration on the burden of AMR in Europe has not yet been comprehensively examined. Therefore, we did a systematic review and meta-analysis to identify and synthesise data for AMR carriage or infection in migrants to Europe to examine differences in patterns of AMR across migrant groups and in different settings. METHODS: For this systematic review and meta-analysis, we searched MEDLINE, Embase, PubMed, and Scopus with no language restrictions from Jan 1, 2000, to Jan 18, 2017, for primary data from observational studies reporting antibacterial resistance in common bacterial pathogens among migrants to 21 European Union-15 and European Economic Area countries. To be eligible for inclusion, studies had to report data on carriage or infection with laboratory-confirmed antibiotic-resistant organisms in migrant populations. We extracted data from eligible studies and assessed quality using piloted, standardised forms. We did not examine drug resistance in tuberculosis and excluded articles solely reporting on this parameter. We also excluded articles in which migrant status was determined by ethnicity, country of birth of participants' parents, or was not defined, and articles in which data were not disaggregated by migrant status. Outcomes were carriage of or infection with antibiotic-resistant organisms. We used random-effects models to calculate the pooled prevalence of each outcome. The study protocol is registered with PROSPERO, number CRD42016043681. FINDINGS: We identified 2274 articles, of which 23 observational studies reporting on antibiotic resistance in 2319 migrants were included. The pooled prevalence of any AMR carriage or AMR infection in migrants was 25·4% (95% CI 19·1-31·8; I2 =98%), including meticillin-resistant Staphylococcus aureus (7·8%, 4·8-10·7; I2 =92%) and antibiotic-resistant Gram-negative bacteria (27·2%, 17·6-36·8; I2 =94%). The pooled prevalence of any AMR carriage or infection was higher in refugees and asylum seekers (33·0%, 18·3-47·6; I2 =98%) than in other migrant groups (6·6%, 1·8-11·3; I2 =92%). The pooled prevalence of antibiotic-resistant organisms was slightly higher in high-migrant community settings (33·1%, 11·1-55·1; I2 =96%) than in migrants in hospitals (24·3%, 16·1-32·6; I2 =98%). We did not find evidence of high rates of transmission of AMR from migrant to host populations. INTERPRETATION: Migrants are exposed to conditions favouring the emergence of drug resistance during transit and in host countries in Europe. Increased antibiotic resistance among refugees and asylum seekers and in high-migrant community settings (such as refugee camps and detention facilities) highlights the need for improved living conditions, access to health care, and initiatives to facilitate detection of and appropriate high-quality treatment for antibiotic-resistant infections during transit and in host countries. Protocols for the prevention and control of infection and for antibiotic surveillance need to be integrated in all aspects of health care, which should be accessible for all migrant groups, and should target determinants of AMR before, during, and after migration. FUNDING: UK National Institute for Health Research Imperial Biomedical Research Centre, Imperial College Healthcare Charity, the Wellcome Trust, and UK National Institute for Health Research Health Protection Research Unit in Healthcare-associated Infections and Antimictobial Resistance at Imperial College London

Early Spectroscopy and Dense Circumstellar Medium Interaction in SN~2023ixf

We present the optical spectroscopic evolution of SN~2023ixf seen in sub-night cadence spectra from 1.18 to 14 days after explosion. We identify high-ionization emission features, signatures of interaction with material surrounding the progenitor star, that fade over the first 7 days, with rapid evolution between spectra observed within the same night. We compare the emission lines present and their relative strength to those of other supernovae with early interaction, finding a close match to SN~2020pni and SN~2017ahn in the first spectrum and SN~2014G at later epochs. To physically interpret our observations we compare them to CMFGEN models with confined, dense circumstellar material around a red supergiant progenitor from the literature. We find that very few models reproduce the blended \NC{} emission lines observed in the first few spectra and their rapid disappearance thereafter, making this a unique diagnostic. From the best models, we find a mass-loss rate of $10^{-3}-10^{-2}$ \mlunit{}, which far exceeds the mass-loss rate for any steady wind, especially for a red supergiant in the initial mass range of the detected progenitor. These mass-loss rates are, however, similar to rates inferred for other supernovae with early circumstellar interaction. Using the phase when the narrow emission features disappear, we calculate an outer dense radius of circumstellar material $R_\mathrm{CSM, out}\sim5\times10^{14}~\mathrm{cm}$ and a mean circumstellar material density of $\rho=5.6\times10^{-14}~\mathrm{g\,cm^{-3}}$. This is consistent with the lower limit on the outer radius of the circumstellar material we calculate from the peak \Halpha{} emission flux, $R_\text{CSM, out}\gtrsim9\times10^{13}~\mathrm{cm}$.Comment: Submitted to ApJ

Huntington's disease and its therapeutic target genes: a global functional profile based on the HD Research Crossroads database.

BACKGROUND: Huntington's disease (HD) is a fatal progressive neurodegenerative disorder caused by the expansion of the polyglutamine repeat region in the huntingtin gene. Although the disease is triggered by the mutation of a single gene, intensive research has linked numerous other genes to its pathogenesis. To obtain a systematic overview of these genes, which may serve as therapeutic targets, CHDI Foundation has recently established the HD Research Crossroads database. With currently over 800 cataloged genes, this web-based resource constitutes the most extensive curation of genes relevant to HD. It provides us with an unprecedented opportunity to survey molecular mechanisms involved in HD in a holistic manner. METHODS: To gain a synoptic view of therapeutic targets for HD, we have carried out a variety of bioinformatical and statistical analyses to scrutinize the functional association of genes curated in the HD Research Crossroads database. In particular, enrichment analyses were performed with respect to Gene Ontology categories, KEGG signaling pathways, and Pfam protein families. For selected processes, we also analyzed differential expression, using published microarray data. Additionally, we generated a candidate set of novel genetic modifiers of HD by combining information from the HD Research Crossroads database with previous genome-wide linkage studies. RESULTS: Our analyses led to a comprehensive identification of molecular mechanisms associated with HD. Remarkably, we not only recovered processes and pathways, which have frequently been linked to HD (such as cytotoxicity, apoptosis, and calcium signaling), but also found strong indications for other potentially disease-relevant mechanisms that have been less intensively studied in the context of HD (such as the cell cycle and RNA splicing, as well as Wnt and ErbB signaling). For follow-up studies, we provide a regularly updated compendium of molecular mechanism, that are associated with HD, at http://hdtt.sysbiolab.eu Additionally, we derived a candidate set of 24 novel genetic modifiers, including histone deacetylase 3 (HDAC3), metabotropic glutamate receptor 1 (GRM1), CDK5 regulatory subunit 2 (CDK5R2), and coactivator 1ß of the peroxisome proliferator-activated receptor gamma (PPARGC1B). CONCLUSIONS: The results of our study give us an intriguing picture of the molecular complexity of HD. Our analyses can be seen as a first step towards a comprehensive list of biological processes, molecular functions, and pathways involved in HD, and may provide a basis for the development of more holistic disease models and new therapeutics