Expression of genes related to Na⁺ exclusion and proline accumulation in tolerant and susceptible wheat genotypes under salt stress

In the present investigation, expression of genes related to Na+ exclusion such as salt overly sensitive (TaSOS1) and Na+/H+ antiporter (TaNHX1) and proline accumulation such as pyrroline-5-carboxylate reductase (P5CR) and glutamate synthase (GOGAT) was studied in seedlings of Kharchia 65 (Kh 65, salt tolerant) and HD 2009 (sensitive) under salt stress (ECe, 12 dSm–1) and controlled conditions. As compared to HD 2009, Kh 65 showed significantly lower accumulation of Na+ (p + exclusion in root and compartmentation in leaf and increased proline concentration are associated with tolerance to salinity stress in wheat. The information will be useful for improving wheat genotypes for salt tolerance

Nematicidal, Fungicidal and Bactericidal Activities of Manganese (II) Complexes with Heterocyclic Sulphonamide Imines

Some manganese(II) complexes derived from different sulphadrugs and heterocyclic ketones have been prepared. These complexes have been characterized on the basis of elemental analyses, molecular weight determinations, conductivity measurements, infrared, ESR and magnetic measurements. The spectral data suggest that the ligands act in a monobasic, bidentate manner coordinating through nitrogen atom. A high spin tetrahedral geometry around this metal has been proposed on the basis of magnetic and spectral studies. The isolated products are coloured solids, soluble in DMSO, DMF and MeOH. All the complexes are monomeric in nature as indicated by their molecular weight determinations and conductivity measurements in dry DMF show them to be non-electrolytes. All the ligands and their corresponding complexes have been screened for their fungicidal, bactericidal and nematicidal activities

The effect of milk type and fortification on the growth of low-birthweight infants: An umbrella review of systematic reviews and meta-analyses

Approximately 15% of infants worldwide are born with low birthweight (<2500 g). These children are at risk for growth failure. The aim of this umbrella review is to assess the relationship between infant milk type, fortification and growth in low-birthweight infants, with particular focus on low- and lower middle–income countries. We conducted a systematic review in PubMed, CINAHL, Embase and Web of Science comparing infant milk options and growth, grading the strength of evidence based on standard umbrella review criteria. Twenty-six systematic reviews qualified for inclusion. They predominantly focused on infants with very low birthweight (<1500 g) in high-income countries. We found the strongest evidence for (1) the addition of energy and protein fortification to human milk (donor or mother's milk) leading to increased weight gain (mean difference [MD] 1.81 g/kg/day; 95% confidence interval [CI] 1.23, 2.40), linear growth (MD 0.18 cm/week; 95% CI 0.10, 0.26) and head growth (MD 0.08 cm/week; 95% CI 0.04, 0.12) and (2) formula compared with donor human milk leading to increased weight gain (MD 2.51 g/kg/day; 95% CI 1.93, 3.08), linear growth (MD 1.21 mm/week; 95% CI 0.77, 1.65) and head growth (MD 0.85 mm/week; 95% CI 0.47, 1.23). We also found evidence of improved growth when protein is added to both human milk and formula. Fat supplementation did not seem to affect growth. More research is needed for infants with birthweight 1500–2500 g in low- and lower middle–income countries

Deoxycholate induces COX-2 expression via Erk1/2-, p38-MAPK and AP-1-dependent mechanisms in esophageal cancer cells

<p>Abstract</p> <p>Background</p> <p>The progression from Barrett's metaplasia to adenocarcinoma is associated with the acquirement of an apoptosis-resistant phenotype. The bile acid deoxycholate (DCA) has been proposed to play an important role in the development of esophageal adenocarcinoma, but the precise molecular mechanisms remain undefined. The aim of this study was to investigate DCA-stimulated COX-2 signaling pathways and their possible contribution to deregulated cell survival and apoptosis in esophageal adenocarcinoma cells.</p> <p>Methods</p> <p>Following exposure of SKGT-4 cells to DCA, protein levels of COX-2, MAPK and PARP were examined by immunoblotting. AP-1 activity was assessed by mobility shift assay. DCA-induced toxicity was assessed by DNA fragmentation and MTT assay.</p> <p>Results</p> <p>DCA induced persistent activation of the AP-1 transcription factor with Fra-1 and JunB identified as the predominant components of the DCA-induced AP-1 complex. DCA activated Fra-1 via the Erk1/2- and p38 MAPK while Erk1/2 is upstream of JunB. Moreover, DCA stimulation mediated inhibition of proliferation with concomitant low levels of caspase-3-dependent PARP cleavage and DNA fragmentation. Induction of the anti-apoptotic protein COX-2 by DCA, via MAPK/AP-1 pathway appeared to balance the DCA mediated activation of pro-apoptotic markers such as PARP cleavage and DNA fragmentation. Both of these markers were increased upon COX-2 suppression by aspirin pretreatment prior to DCA exposure.</p> <p>Conclusion</p> <p>DCA regulates both apoptosis and COX-2-regulated cell survival in esophageal cells suggesting that the balance between these two opposing signals may determine the transformation potential of DCA as a component of the refluxate.</p

Recombinant Lysyl Oxidase Propeptide Protein Inhibits Growth and Promotes Apoptosis of Pre-Existing Murine Breast Cancer Xenografts

Lysyl oxidase propeptide (LOX-PP) ectopic overexpression inhibits the growth of cancer xenografts. Here the ability and mode of action of purified recombinant LOX-PP (rLOX-PP) protein to inhibit the growth of pre-existing xenografts was determined. Experimental approaches employed were direct intratumoral injection (i.t.) of rLOX-PP protein into murine breast cancer NF639 xenografts, and application of a slow release formulation of rLOX-PP implanted adjacent to tumors in NCR nu/nu mice (n = 10). Tumors were monitored for growth, and after sacrifice were subjected to immunohistochemical and Western blot analyses for several markers of proliferation, apoptosis, and for rLOX-PP itself. Direct i.t. injection of rLOX-PP significantly reduced tumor volume on days 20, 22 and 25 and tumor weight at harvest on day 25 by 30% compared to control. Implantation of beads preloaded with 35 micrograms rLOX-PP (n = 10) in vivo reduced tumor volume and weight at sacrifice when compared to empty beads (p<0.05). A 30% reduction of tumor volume on days 22 and 25 (p<0.05) and final tumor weight on day 25 (p<0.05) were observed with a reduced tumor growth rate of 60% after implantation. rLOX-PP significantly reduced the expression of proliferation markers and Erk1/2 MAP kinase activation, while prominent increases in apoptosis markers were observed. rLOX-PP was detected by immunohistochemistry in harvested rLOX-PP tumors, but not in controls. Data provide pre-clinical findings that support proof of principle for the therapeutic anti-cancer potential of rLOX-PP protein formulations

Dementia diagnosis in seven languages: the Addenbrooke’s Cognitive Examination-III in India

OBJECTIVE: With the rising burden of dementia globally, there is a need to harmonize dementia research across diverse populations. The Addenbrooke's Cognitive Examination-III (ACE-III) is a well-established cognitive screening tool to diagnose dementia. But there have been few efforts to standardize the use of ACE-III across cohorts speaking different languages. The present study aimed to standardize and validate ACE-III across seven Indian languages and to assess the diagnostic accuracy of the test to detect dementia and mild cognitive impairment (MCI) in the context of language heterogeneity.  METHODS: The original ACE-III was adapted to Indian languages: Hindi, Telugu, Kannada, Malayalam, Urdu, Tamil, and Indian English by a multidisciplinary expert group. The ACE-III was standardized for use across all seven languages. In total, 757 controls, 242 dementia, and 204 MCI patients were recruited across five cities in India for the validation study. Psychometric properties of adapted versions were examined and their sensitivity and specificity were established.  RESULTS: The sensitivity and specificity of ACE-III in identifying dementia ranged from 0.90 to 1, sensitivity for MCI ranged from 0.86 to 1, and specificity from 0.83 to 0.93. Education but not language was found to have an independent effect on ACE-III scores. Optimum cut-off scores were established separately for low education (≤10 years of education) and high education (>10 years of education) groups.  CONCLUSIONS: The adapted versions of ACE-III have been standardized and validated for use across seven Indian languages, with high diagnostic accuracy in identifying dementia and MCI in a linguistically diverse context

The Na+/H+ Exchanger Controls Deoxycholic Acid-Induced Apoptosis by a H+-Activated, Na+-Dependent Ionic Shift in Esophageal Cells

Apoptosis resistance is a hallmark of cancer cells. Typically, bile acids induce apoptosis. However during gastrointestinal (GI) tumorigenesis the cancer cells develop resistance to bile acid-induced cell death. To understand how bile acids induce apoptosis resistance we first need to identify the molecular pathways that initiate apoptosis in response to bile acid exposure. In this study we examined the mechanism of deoxycholic acid (DCA)-induced apoptosis, specifically the role of Na+/H+ exchanger (NHE) and Na+ influx in esophageal cells. In vitro studies revealed that the exposure of esophageal cells (JH-EsoAd1, CP-A) to DCA (0.2 mM -0.5 mM) caused lysosomal membrane perturbation and transient cytoplasmic acidification. Fluorescence microscopy in conjunction with atomic absorption spectrophotometry demonstrated that this effect on lysosomes correlated with influx of Na+, subsequent loss of intracellular K+, an increase of Ca2+ and apoptosis. However, ethylisopropyl-amiloride (EIPA), a selective inhibitor of NHE, prevented Na+, K+ and Ca2+ changes and caspase 3/7 activation induced by DCA. Ouabain and amphotericin B, two drugs that increase intracellular Na+ levels, induced similar changes as DCA (ion imbalance, caspase3/7 activation). On the contrary, DCA-induced cell death was inhibited by medium with low a Na+ concentrations. In the same experiments, we exposed rat ileum ex-vivo to DCA with or without EIPA. Severe tissue damage and caspase-3 activation was observed after DCA treatment, but EIPA almost fully prevented this response. In summary, NHE-mediated Na+ influx is a critical step leading to DCA-induced apoptosis. Cells tolerate acidification but evade DCA-induced apoptosis if NHE is inhibited. Our data suggests that suppression of NHE by endogenous or exogenous inhibitors may lead to apoptosis resistance during GI tumorigenesis

Mortality and pulmonary complications in patients undergoing surgery with perioperative sars-cov-2 infection: An international cohort study

Background The impact of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) on postoperative recovery needs to be understood to inform clinical decision making during and after the COVID-19 pandemic. This study reports 30-day mortality and pulmonary complication rates in patients with perioperative SARS-CoV-2 infection. Methods This international, multicentre, cohort study at 235 hospitals in 24 countries included all patients undergoing surgery who had SARS-CoV-2 infection confirmed within 7 days before or 30 days after surgery. The primary outcome measure was 30-day postoperative mortality and was assessed in all enrolled patients. The main secondary outcome measure was pulmonary complications, defined as pneumonia, acute respiratory distress syndrome, or unexpected postoperative ventilation. Findings This analysis includes 1128 patients who had surgery between Jan 1 and March 31, 2020, of whom 835 (740%) had emergency surgery and 280 (248%) had elective surgery. SARS-CoV-2 infection was confirmed preoperatively in 294 (261%) patients. 30-day mortality was 238% (268 of 1128). Pulmonary complications occurred in 577 (512%) of 1128 patients; 30-day mortality in these patients was 380% (219 of 577), accounting for 817% (219 of 268) of all deaths. In adjusted analyses, 30-day mortality was associated with male sex (odds ratio 175 [95% CI 128-240], p&lt;00001), age 70 years or older versus younger than 70 years (230 [165-322], p&lt;00001), American Society of Anesthesiologists grades 3-5 versus grades 1-2 (235 [157-353], p&lt;00001), malignant versus benign or obstetric diagnosis (155 [101-239], p=0046), emergency versus elective surgery (167 [106-263], p=0026), and major versus minor surgery (152 [101-231], p=0047). Interpretation Postoperative pulmonary complications occur in half of patients with perioperative SARS-CoV-2 infection and are associated with high mortality. Thresholds for surgery during the COVID-19 pandemic should be higher than during normal practice, particularly in men aged 70 years and older. Consideration should be given for postponing non-urgent procedures and promoting non-operative treatment to delay or avoid the need for surgery. Funding National Institute for Health Research (NIHR), Association of Coloproctology of Great Britain and Ireland, Bowel and Cancer Research, Bowel Disease Research Foundation, Association of Upper Gastrointestinal Surgeons, British Association of Surgical Oncology, British Gynaecological Cancer Society, European Society of Coloproctology, NIHR Academy, Sarcoma UK, Vascular Society for Great Britain and Ireland, and Yorkshire Cancer Research

Effects of hospital facilities on patient outcomes after cancer surgery: an international, prospective, observational study

Background Early death after cancer surgery is higher in low-income and middle-income countries (LMICs) compared with in high-income countries, yet the impact of facility characteristics on early postoperative outcomes is unknown. The aim of this study was to examine the association between hospital infrastructure, resource availability, and processes on early outcomes after cancer surgery worldwide.Methods A multimethods analysis was performed as part of the GlobalSurg 3 study-a multicentre, international, prospective cohort study of patients who had surgery for breast, colorectal, or gastric cancer. The primary outcomes were 30-day mortality and 30-day major complication rates. Potentially beneficial hospital facilities were identified by variable selection to select those associated with 30-day mortality. Adjusted outcomes were determined using generalised estimating equations to account for patient characteristics and country-income group, with population stratification by hospital.Findings Between April 1, 2018, and April 23, 2019, facility-level data were collected for 9685 patients across 238 hospitals in 66 countries (91 hospitals in 20 high-income countries; 57 hospitals in 19 upper-middle-income countries; and 90 hospitals in 27 low-income to lower-middle-income countries). The availability of five hospital facilities was inversely associated with mortality: ultrasound, CT scanner, critical care unit, opioid analgesia, and oncologist. After adjustment for case-mix and country income group, hospitals with three or fewer of these facilities (62 hospitals, 1294 patients) had higher mortality compared with those with four or five (adjusted odds ratio [OR] 3.85 [95% CI 2.58-5.75]; p&lt;0.0001), with excess mortality predominantly explained by a limited capacity to rescue following the development of major complications (63.0% vs 82.7%; OR 0.35 [0.23-0.53]; p&lt;0.0001). Across LMICs, improvements in hospital facilities would prevent one to three deaths for every 100 patients undergoing surgery for cancer.Interpretation Hospitals with higher levels of infrastructure and resources have better outcomes after cancer surgery, independent of country income. Without urgent strengthening of hospital infrastructure and resources, the reductions in cancer-associated mortality associated with improved access will not be realised