Bioclimatic modeling and FACE study forecast a bleak future for wheat production in India.

Since the impact of future climate change on wheat productivity is inconsistent, we studied geographic distribution and yield of wheat using two global General Circulation Models (GCMs) and Free Air CO2/O3 Enrichment (FACE) experiments. The GCMs (IPSL-CM5A-LR and NIMR-HADGEM2-AO) with four Representative Concentration Pathways (RCPs) and 19 bioclimatic variables were used for distribution/ecological niche modeling (ENM). Currently cultivated eight wheat cultivars were exposed to individual treatment of (i) ambient CO2, temperature, and ozone (ACO + AO + AT) representing the present climate scenario, and (ii) elevated CO2 (550 ppm) (ECO), (iii) elevated temperature (+ 2 °C) (ET), (iv) elevated O3 (ambient + 20 ppb) (EO), (v) elevated CO2 + elevated O3 (ECO + EO), and (vi) elevated CO2 + elevated temperature + elevated O3 (ECO + EO + ET) under FACE facility simulating the future climate change scenarios in 2050. The niche models predicted a reduction in climatically suitable areas for wheat, and identified "maximum temperature" as the most influencing factor for area reduction. The elevated CO2, O3, and temperature individually and in combinations had differential impacts on the yield of wheat cultivars. Only two cultivars, viz., DBW 184 and DBW 187 did not exhibit yield decline suggesting their suitability in the future climate change scenario. Since the performance of six out of eight cultivars significantly declined under simulated FACE experiment, and ENM predicted reduction in wheat cultivation area under RCP 8.5 in 2050, it was concluded that future of wheat cultivation in India is bleak. The study further indicates that coupling of bioclimatic modeling and FACE experiment can effectively predict the impact of climate change on different crops.

Correlation between Sonoelastography and Histopathological Findings in Evaluation of Chronic Renal Allograft Disease.

Background Non-invasive evaluation tool for allograft kidney is important to predict chronic allograft dysfunction as it can be alternative to the invasive biopsy which is prone to so many complications. Sonoelastography can assess the stiffness of the allograft renal parenchyma, which is prone to undergo interstitial fibrosis. Objective To correlate sonoelastography with histopathology findings in the renal allografts. Method Sonoelastography was done in 60 renal allograft recipients prior to their biopsy for various indications. Estimated glomerular filtration rate (eGFR) of the patient were also obtained. Histopathology reports were collected to determine Banff score of interstitial fibrosis. Descriptive measurements (Mean ± standard deviation, Frequencies, Proportions) were calculated. Correlations among the variables were measured using Pearson's correlation, independent sample t-test, and ANOVA. Result The mean strain index (SI) was lower in higher grades of fibrosis. There was significant difference in mean SI (F=18.264; df= 2,57; p < 0.001) among the histological grades of fibrosis. Also a significant difference in SI among mild and moderate (S.E. 0.27, p value < 0.001), mild and severe (S.E. 0.213, p value < 0.001) as well as moderate and severe fibrosis (S.E. 0.244, p value < 0.001) was seen. Significant correlation of eGFR with SI (p < 0.001) was also seen. Conclusion Strain index, measured with sonoelastography, significantly correlated with different grades of tissue fibrosis. Thus it can be used as alternative method for evaluation of renal allograft patients to avoid complications of biopsy.

Energy and carbon budgeting of traditional land use change with groundnut based cropping system for environmental quality, resilient soil health and farmers income in eastern Indian Himalayas.

Energy intensive traditional cereals based monoculture often lead to high greenhouse gas emissions and degradation of land and environmental quality. Present study aimed at evaluating the energy and carbon budget of diversified groundnut (Arachis hypogea L) based cropping system with over existing traditional practice towards the development of a sustainable production technology through restoration of soil and environmental quality and enhancement of farming resiliency by stabilizing farmers' income. The trials comprised of three introduced groundnut based systems viz. groundnut- pea (Pisum sativum), groundnut-lentil (Lens esculenta) and groundnut-toria (Brasssica campestris var. Toria) replacing three existing systems viz. maize (Zea mays L) - fallow, maize - toria, and rice (Oryza sativa L)-fallow systems. Four years study revealed that adoption of groundnut based systems reduced non-renewable energy input use (fertilizers, chemical, machinery and fossil fuels) by 25.5%, consequently that reduced the cost of production. Repeated analysis of variance measurement also affirmed that groundnut based systems (groundnut-pea>groundnut-lentil> groundnut-toria) increased the energy use efficiency, energy productivity, carbon use efficiency, net returns and decreased the specific energy and energy intensiveness. Groundnut based systems increased the mean system productivity and water productivity in terms of groundnut equivalent yield by 3.7 and 3.1 folds over existing practice. The savings of fossil fuel reduced greenhouse gas emissions owing to reduced use of farm machinery and synthetic fertilizers. Groundnut based systems significantly (p < 0.05) enhanced the soil carbon concentration (8.7-18.1%) and enzymatic activities (27.1-51.8%) over existing practice. Consequently, estimated soil quality index values were 35.9-77.3% higher under groundnut based systems than existing practice. Thus, the study indicated the resilient nature of groundnut based systems as an environmentally safe and sustainable production technology for enhancing resource use efficiency, reduce carbon emission, energy intensiveness and cost of production in the Eastern Himalaya region of India and similar ecosystems.

Sonographic Quantification of Ovarian Volume in Adults Attending General Health Checkup and General Out Patient Department in Tribhuvan University Teaching Hospital.

Background Ultrasonography is the easily available, cheap and reliable method for evaluation of ovaries. Ovarian volume is the major factor in the diagnosis of various ovarian pathologies and confusing discrepancies are found in the literature. Objective To determine the ovarian volume among individuals attending outpatient department in tertiary level hospital. Method Descriptive cross sectional study design was used; 305 patients of 16-60 years attending general outpatient department in the Tribhuvan University Teaching Hospital, Kathmandu, Nepal were included. Ovarian volume was calculated by using transabdominal ultrasonography. Data was collected in the predesigned proforma and analyzed using statistical package for the social sciences software. Result The study showed mean total ovarian volume 5.95 ± 2.44 cc (centimeter cube) with mean right ovarian volume 5.94 ± 2.70 cc and mean left ovarian volume 6.05 ± 2.79 cc. Significant decrease in ovarian volume with age was observed. Height and weight did not show significant correlation with ovarian volumes and no significant variation seen in the volumes of right and left ovaries. Periovulatory ovaries show significantly higher volumes on right side than luteal phase. Similarly, significantly higher volume of left ovary seen in mixed ethnic group than mongoloid group. Conclusion Measurement of ovarian volume is important for evaluation and management of ovarian disorders. Ultrasonography which is readily available, simple and cost effective is better suited for our environment than other imaging modality. Values of ovarian volume from this study may provide a baseline of normal ovarian volume in our community.

Investigation of belinostat-induced genomic instability by molecular cytogenetic analysis and pathway-focused gene expression profiling.

Histone deacetylases (HDACs), which regulate transcription and specific functions such as tumor suppression by p53, are frequently altered in tumors and have a contentious role in carcinogenesis. HDAC inhibitors, which have a long history of use in psychiatry and neurology, have recently been tested as possible treatments for tumors. Belinostat received regulatory approval in the USA on July 3, 2014, for use against peripheral T-cell lymphoma. However, the unavailability of information on belinostat genotoxicity in normal cells and the molecular mechanisms involved in the genetic instability after exposure to belinostat encouraged us to conduct this study. Our data showed that the exposure of mice to belinostat at the recommended human doses induced chromosome breakage, whole-chromosome lagging, and oxidative DNA damage in bone marrow cells in a dose-dependent manner. The expression levels of 84 genes involved in the DNA damage signaling pathway were evaluated by using an RT2 Profiler PCR array. Belinostat exposure altered the expression of 25 genes, with statistically significant changes observed in 17 genes. The array results were supported by RT-PCR and western blotting experiments. Collectively, our results showed that belinostat exposure caused oxidative DNA damage and downregulated the expression of genes involved in DNA damage repair, which may be responsible for belinostat-induced genomic instability. Thus, the clinical usage of this drug should be weighed against the hazards of carcinogenesis, and the observed genotoxicity profile of belinostat may support further development of efficient HDAC inhibitors with weaker genotoxicity.

Efficacy of Cell Wall-Deficient Spheroplasts Against Experimental Murine Listeriosis.

Various strategies adapted to develop an efficient vaccine against foodborne pathogen, Listeria monocytogenes, have met with little success. Spheroplasts (bacterial cell devoid of cell wall) are likely to undergo membrane-membrane fusion, leading to the delivery of their content to the cytosol of antigen-presenting cells, thus facilitating MHC class I antigen processing and presentation. In this study, we evaluated the prophylactic potential of Listeria spheroplast-based vaccine against experimental murine listeriosis in comparison with heat-killed Listeria (HKL) and archaeosome-entrapped Listeria whole-cell protein (LWCP). Compared with HKL, the spheroplast-based vaccine was found to evoke better Th1 response as exhibited by the presence of type 1 cytokines in the host (interferon-γ and IL-12) and a high IgG2a /IgG1 ratio. Robust lympho-proliferative efficacy was apparent in both spheroplast-immunized and archaeosome-entrapped LWCP-immunized groups. The upregulation of costimulatory and effector memory markers upon immunization with spheroplasts was found to be at par with that evoked by archaeosome-entrapped LWCP-immunized group. Central memory response in gated CD8(+) T cell was much higher in spheroplast-immunized animals when compared with archaeosome-entrapped LWCP group. The data presented here clearly demonstrate that spheroplasts evoked a robust immune response and offer better prophylactic potential against L. monocytogenes.

Interaction of Al(2)O(3) nanoparticles with Escherichia coli and their cell envelope biomolecules.

AIMS: The aim of this study is to investigate the antibacterial activity of aluminium oxide nanoparticles (Al2 O3 NPs) against multidrug-resistant clinical isolates of Escherichia coli and their interaction with cell envelope biomolecules. METHODS AND RESULTS: Al2 O3 NPs were characterized by scanning electron microscope (SEM), high-resolution transmission electron microscope (HR-TEM) and X-ray diffraction (XRD) analyses. Antibacterial activity and interaction of Al2 O3 NPs with E. coli and its surface biomolecules were assessed by spectrophotometry, SEM, HR-TEM and attenuated total reflectance/Fourier transform infrared (ATR-FTIR). Of the 80 isolates tested, about 64 (80%) were found to be extended spectrum ß-lactamase (ESBL) positive and 16 (20%) were non-ESBL producers. Al2 O3 NPs at 1000 µg ml(-1) significantly inhibited the bacterial growth. SEM and HR-TEM analyses revealed the attachment of NPs to the surface of cell membrane and also their presence inside the cells due to formation of irregular-shaped pits and perforation on the surfaces of bacterial cells. The intracellular Al2 O3 NPs might have interacted with cellular biomolecules and caused adverse effects eventually triggering the cell death. ATR-FTIR studies suggested the interaction of lipopolysaccharide (LPS) and L-α-Phosphatidyl-ethanolamine (PE) with Al2 O3 NPs. Infrared (IR) spectral changes revealed that the LPS could bind to Al2 O3 NPs through hydrogen binding and ligand exchange. The Al2 O3 NPs-induced structural changes in phospholipids may lead to the loss of amphiphilic properties, destruction of the membrane and cell leaking. CONCLUSIONS: The penetration and accumulation of NPs inside the bacterial cell cause pit formation, perforation and disorganization and thus drastically disturb its proper function. The cell surface biomolecular changes revealed by ATR-FTIR spectra provide a better understanding of the cytotoxicity of Al2 O3 NPs. SIGNIFICANCE AND IMPACT OF THE STUDY: Al2 O3 NPs may serve as broad-spectrum bactericidal agents to control the emergent pathogens regardless of their drug-resistance mechanisms.

Correlation between serum galanin and neuron-specific enolase levels with EEG abnormalities in pediatric convulsive status epilepticus and the efficacy of triple drug therapy.

OBJECTIVE: This study aimed to investigate the association between serum galanin (GAL) and neuron-specific enolase (NSE) levels in children with convulsive status epilepticus (CSE) and their relationship with abnormal electroencephalogram (EEG) patterns. Additionally, the study assessed the effectiveness of a combination therapy involving midazolam, diazepam, and phenobarbital in treating CSE. PATIENTS AND METHODS: The research involved 100 children diagnosed with CSE and included a control group of 50 healthy children. Serum GAL and NSE levels were measured, and EEGs were analyzed for abnormalities in the CSE group. Comparisons were made between the healthy control group and the CSE group, particularly within the first 24 hours after persistent seizures. The severity of EEG abnormalities was correlated with GAL and NSE levels. The treatment consisted of an observation group that received the triple therapy of midazolam, diazepam, and phenobarbital, while a control group received diazepam and phenobarbital. Clinical efficacy, symptom improvement, Status Epilepticus Severity Score (STESS), and adverse reactions were evaluated. RESULTS: The results indicated elevated levels of GAL and NSE in the CSE group, with higher levels noted within 24 hours after persistent seizures. Furthermore, a positive correlation was observed between the severity of EEG abnormalities and GAL and NSE levels. The group receiving the triple therapy demonstrated superior efficacy, faster resolution of seizures and fever, reduced STESS scores, and fewer adverse reactions than the control group. In conclusion, this study highlights the positive correlation between serum GAL and NSE levels and the severity of EEG abnormalities in pediatric CSE. The triple therapy approach is effective in treating CSE, leading to improved clinical symptoms, reduced brain damage, and enhanced safety. CONCLUSIONS: The study concludes that serum GAL and NSE levels in children with convulsive status epilepticus are positively correlated with the degree of EEG abnormalities. The combination therapy involving midazolam, diazepam, and phenobarbital is effective in treating children with convulsive status epilepticus, significantly improving clinical symptoms, reducing brain damage, and ensuring safety.

Blood-based microRNA profiling unveils complex molecular dynamics in breast cancer.

BACKGROUND: Breast cancer, a genetically intricate disease with diverse subtypes, exhibits heightened incidence globally. In this study, we aimed to investigate blood-based microRNAs (miRNAs) as potential biomarkers for breast cancer. The primary objectives were to explore the role of miRNAs in cancer-related processes, assess their differential expression between breast cancer patients and healthy individuals, and contribute to a deeper understanding of the molecular underpinnings of breast cancer. METHODS: MiRNA extraction was performed on 40 breast cancer patients and adjacent normal tissues using a commercial RNA isolation kit. Total RNA quantification and quality assessment were conducted with advanced technologies. MiRNA profiling involved reverse transcription, labeling, and hybridization on Agilent human miRNA arrays (V2). Bioinformatics analysis utilized the DIANA system for target gene prediction and the DIANA-mirPath tool for pathway enrichment analysis. Selected miRNAs underwent validation through quantitative real-time PCR. RESULTS: Principal component analysis revealed overlapping miRNA expression patterns in primary and malignant breast tumors, underscoring the genetic complexity involved. Statistical analysis identified 54 downregulated miRNAs in malignant tumors and 38 in primary tumors compared to controls. Bioinformatics analysis implicated several pathways, including Wnt, TGF-b, ErbB, and MAPK signaling. Validation through qRT-PCR confirmed altered expression of hsa-miR-130a, hsa-miR-21, hsa-miR-223, and hsa-let-7c key miRNAs, highlighting their significance in breast cancer. The results from microarray were further validated by qPCR and the expression of which are downregulated in breast cancer was detected. CONCLUSION: This study provides significant insights into distinct miRNA expression patterns in normal and malignant breast tissues. The overlapping miRNA profiles in primary and malignant tumors underscore the complexity of genetic regulation in breast cancer. The identification of deregulated miRNAs and affected pathways contributes to our understanding of breast cancer pathogenesis. The validated miRNAs hold potential as diagnostic and prognostic markers, offering avenues for further clinical exploration in breast cancer research.

Computational ensemble expert system classification for the recognition of bruxism using physiological signals.

This study aimed to develop an automatic diagnostic scheme for bruxism, a sleep-related disorder characterized by teeth grinding and clenching. The aim was to improve on existing methods, which have been proven to be inefficient and challenging. We utilized a novel hybrid machine learning classifier, facilitated by the Weka tool, to diagnose bruxism from biological signals. The study processed and examined these biological signals by calculating the power spectral density. Data were categorized into normal or bruxism categories based on the EEG channel (C4-A1), and the sleeping phases were classified into wake (w) and rapid eye movement (REM) stages using the ECG channel (ECG1-ECG2). The classification resulted in a maximum specificity of 93% and an accuracy of 95% for the EEG-based diagnosis. The ECG-based classification yielded a supreme specificity of 87% and an accuracy of 96%. Furthermore, combining these phases using the EMG channel (EMG1-EMG2) achieved the highest specificity of 95% and accuracy of 98%. The ensemble Weka tool combined all three physiological signals EMG, ECG, and EEG, to classify the sleep stages and subjects. This integration increased the specificity and accuracy to 97% and 99%, respectively. This indicates that a more precise bruxism diagnosis can be obtained by including all three biological signals. The proposed method significantly improves bruxism diagnosis accuracy, potentially enhancing automatic home monitoring systems for this disorder. Future studies may expand this work by applying it to patients for practical use.

Risk factors for postoperative complications in preterm infants with surgical necrotizing enterocolitis and associated outcomes.

BACKGROUND: We aim to determine clinical risk factors for postoperative complications in preterm infants with surgical necrotizing enterocolitis (NEC) or spontaneous intestinal perforation (SIP). METHODS: A retrospective cohort study of preterm infants with surgical NEC or SIP to compare clinical factors between those with and without postoperative complications. RESULTS: 78/109 (71.5%) infants had any complication following surgical NEC. Adhesions (20/35, 57.1%) and wound infection (6/35, 17.1%) were the most common single surgical complications. Patients with a single surgical complication (35/66, 53%) were significantly less likely to be exposed to antenatal steroids, more frequently had a jejunostomy, needed a central line longer, and had a longer length of stay than those without any surgical complication. Infants with > 1 surgical complication (43/71, 60.5%) included mainly females, and had AKI more frequently at NEC onset, lower weight z-scores and lower weight for length z- scores at 36 weeks PMA than those without any complications.On multinomial logistic regression, antenatal steroids exposure (OR 0.23 [CI 0.06, 0.84]; p = 0.027) was independently associated with lower risk and jejunostomy 4.81 (1.29, 17.9) was independently associated with higher risk of developing a single complication. AKI following disease onset (OR 5.33 (1.38, 20.6), P = 0.015) was independently associated with > 1 complication in surgical NEC/SIP infants. CONCLUSION: Infants with postoperative complications following surgical NEC were more likely to be female, have additional morbidities, and demonstrate growth failure at 36 weeks PMA than those without surgical complications. There was no difference in mortality between those with and without surgical complications.

Partial role of multiple pathways in infarct size limiting effect of quercetin and rutin against cerebral ischemia-reperfusion injury in rats.

BACKGROUND: Reperfusion therapy used in the treatment of cerebral ischemia often causes reperfusion neurological injury. Multiple pathological processes are involved in this injury including oxidative stress and components of the inflammatory response appear to play key roles in these deleterious effects. Thus new therapeutic strategies aimed at neutralization of OS-induced neurotoxicity support the application of natural antioxidant bioflavonoids. Both experimental and epidemiological evidence demonstrate that bioflavonoid such as quercetin and rutin are neuroprotective in models of cerebral ischemia reperfusion injury. However, recent studies indicate that the radical scavenger property of quercetin and rutin is unlikely to be the only reason for their cerebroprotective actions and in fact, a wide spectrum of cellular signaling events may well account for their biological actions. AIM: In this study we attempted to establish the various mechanisms involved in the cerebroprotective activity of quercetin and rutin. METHODS: Adult Sprague Dawely rats were anesthetized with thiopentone and subjected to global cerebral ischemia by occlusion of bicommon carotid arteries. Infarct size (TTC staining), SOD, MDA, CAT and MPO levels was assessed 4 h after the onset of ischemia. RESULTS: Quercetin (50 mg/kg) and rutin (10 mg/kg) administered 10 min before reperfusion resulted in significant reduction of infarct size, MDA, and MPO levels and significant increase in SOD and CAT levels. Administration of L-NAME prior to administration of quercetin and rutin, significantly reduced the cerebroprotection offered by quercetin and rutin. CONCLUSIONS: Possible partial role of antioxidant, anti-inflammatory and involvement of NO in the beneficial effects of bioflavonoids quercetin and rutin against cerebral ischemia reperfusion injury was observed.

Neuroprotective effect of allopurinol and nimesulide against cerebral ischemic reperfusion injury in diabetic rats.

OBJECTIVES: The main objective of the study was to determine the neuroprotective effect of allopurinol and nimesulide against the cerebral ischemic reperfusion injury in diabetic and nondiabetic rats. MATERIALS AND METHODS: In this study, Wistar albino rats of either sex weighing 150-250 g were procured from authorized suppliers. Rats were anesthetized by giving thiopentone sodium (45 mg/kg) by i.p. Under anesthesia, midline incision was given. Common carotid arteries were identified and isolated carefully from vago-sympathetic nerve. Rats were made ischemic by occluding bicommon carotid arteries with thread for 30 min, followed by reperfusion for 4 h by removing the occlusion. The drugs allopurinol (15, 30 mg/kg) and nimesulide (20, 40 mg/kg) were administered 10 min before reperfusion. Then after 4 h reperfusion, animals were sacrificed and immediately brain was removed, homogenized, centrifuged and supernatant was collected, various enzyme estimations were done and same procedure was followed in streptozotocin (STZ: 45 mg/kg; i.p.) induced diabetic rats. RESULTS: Ischemia reperfusion (I/R) group showed significant increase in malondialdehyde (MDA), myeloperoxidase (MPO) and depletion in catalase (CAT) and superoxide dismutase (SOD) levels. Treatment with allopurinol and nimesulide significantly decreased the MDA and MPO levels whereas increased the SOD and CAT levels when compared I/R group in both non-diabetic and diabetic rats. CONCLUSIONS: These findings suggest the cerebral injury due to over production of free radicals was inhibited by allopurinol and nimesulide that exert a neuroprotective effect probably by radical scavenging and antioxidant activities.

Ossification of Superior Transverse Scapular Ligament - Incidence, Embryology and Association with Suprascapular Neuropathy.

Introduction: Suprascapular notch is present at superior border of scapula just medial to coracoid process. This is covered by superior transverse scapular ligament (STSL). Suprascapular nerve passes below this ligament while suprascapular vessels pass above it. STSL ossification is a rare finding with variable incidences in different population groups. Materials and Methods: We observed 60 dry bony scapulae, 30 prosected formalin fixed upper limbs with scapula and 10 embalmed cadavers for the presence of ossified STSL. Results: There were complete ossification of STSL in two dried bony specimens of sacpula. Conclusion: Ossified STSL may be the causative factor for suprascapular neuropathy. The mainstay of management in cases of neuropathy or compression of suprascapular nerve is release of suprascapular ligament by either open or arthroscopic surgical approach. So, it is extremely important to know this type of variation to minimize any damage to related structure and plan the management accordingly.

Correlation of placental pathology with the postoperative outcomes and white matter injury in preterm infants following necrotizing enterocolitis.

BACKGROUND: To determine the association of placental pathologic lesions with postoperative outcomes, survival, and white matter injury (WMI) in preterm infants with NEC. METHODS: A retrospective chart review of 107 neonates with NEC (Bell stage > IIa) from Jan 2013- June 2020 was completed. Demographic, clinical, and outcome data were compared between infants with or without placental pathologic lesions. RESULTS: In this cohort, 59/107 (55%) infants had medical NEC, and 48 (45%) had surgical NEC. The infants had a mean gestational age of 28.1±3.7 weeks and a birth weight of 1103±647 g. Maternal vascular malperfusion (82/107, 76.6%) and acute histological chorioamnionitis (42, 39.3%) were the most common pathological placental lesions. Acute histologic chorioamnionitis with fetal inflammatory response was more common in infants with surgical NEC vs. medical NEC (35.4% vs. 15.3%; p = 0.02). The NEC Infants with WMI on brain MRI scans had a significantly higher incidence of acute histological chorioamnionitis (52% vs. 27.8%; P = 0.04). No significant differences in mortality, length of stay and postoperative outcomes in neonates with and without acute histologic chorioamnionitis with fetal inflammatory response were noted. On unadjusted logistic regression, acute histologic chorioamnionitis without fetal inflammatory response was also associated with higher odds of WMI (OR 2.81; 95% CI 1.05-7.54; p = 0.039). CONCLUSION: Acute histological chorioamnionitis without fetal inflammatory response was associated with higher odds of WMI in infants with NEC, with no significant impact on mortality and other postoperative outcomes.

The small molecule Erk1/2 signaling pathway inhibitor PD98059 improves DNA repair in an experimental autoimmune encephalomyelitis SJL/J mouse model of multiple sclerosis.

Multiple sclerosis (MS) is a demyelinating disorder in which the myelin sheath covering the central nervous system axons is damaged or lost, disrupting action potential conduction and leading to various neurological complications. The pathogenesis of MS remains unclear, and no effective therapies are currently available. MS is triggered by environmental factors in genetically susceptible individuals. DNA damage and DNA repair failure have been proposed as MS genetic risk factors; however, inconsistent evidence has been found in multiple studies. Therefore, more investigations are needed to ascertain whether DNA damage/repair is altered in this disorder. In this context, therapies that prevent DNA damage or enhance DNA repair could be effective strategies for MS treatment. The overactivation of the extracellular-signal-related kinase 1 and 2 (Erk1/2) pathway can lead to DNA damage and has been linked to MS pathogenesis. In our study, we observed substantially elevated oxidative DNA damage and slower DNA repair rates in an experimentally autoimmune encephalomyelitis animal model of MS (EAE). Moreover, statistical decreases in oxidative DNA strand breaks and faster repair rates were observed in EAE animals injected with the Erk1/2 inhibitor PD98059 (PD). Moreover, the expression of several genes associated with DNA strand breaks and repair changed in EAE mice at both the mRNA and protein levels, as revealed by the RT2 Profiler PCR array and verified by RT-PCR and protein analyses. The treatment with PD mitigated these changes and improved DNA repair gene expression. Our results demonstrate clear associations between Erk1/2 activation, DNA damage/repair, and MS pathology, and further suggest that PD therapy may be a promising adjuvant therapeutic strategy.

Clinical determinants of intestinal failure and death in preterm infants with surgical necrotizing enterocolitis.

OBJECTIVE: We sought to investigate the clinical determinants of intestinal failure and death in preterm infants with surgical NEC. METHODS: Retrospective comparison of clinical information between Group A = intestinal failure (Parenteral nutrition (PN) >90 days) and death and Group B = survivors and with PN dependence < 90 days in preterm infants with surgical NEC. RESULTS: Group A (n = 99/143) had a lower mean gestational age (26.4 weeks [SD3.5] vs. 29.4 [SD 3.5]; p = 0.013), lower birth weight (873 gm [SD 427g] vs. 1425 gm [894g]; p = <0.001), later age of NEC onset (22 days [SD20] vs. 16 days [SD 17]; p = 0.128), received surgery later (276 hours [SD 544] vs. 117 hours [SD 267]; p = 0.032), had cholestasis, received dopamine (80.6% vs. 58.5%; p = 0.010) more frequently and had longer postoperative ileus time (19.8 days [SD 15.4] vs. 11.8 days [SD 6.5]; p = <0.001) and reached full feeds later (93 days [SD 45] vs. 44 [SD 22]; p = <0.001) than Group B.On multivariate logistic regression, higher birth weight was associated with lower risk (OR 0.35, 95% CI 0.15-0.82; p = 0.016) of TPN > 90 days or death. Longer length of bowel resected (OR 1.76, 95% CI 1.02-3.02; p = 0.039) and longer postoperative ileus (OR 2.87, 95% CI 1.26-6.53; p = 0.011) were also independently associated with TPN >90days or death adjusted for gestational age and antenatal steroid treatment. CONCLUSION: In preterm infants with surgical NEC, clinical factors such as lower birth weight, longer bowel loss, and postoperative ileus days were significantly and independently associated with TPN >90 days or death.

Diagnosis of hypercritical chronic pulmonary disorders using dense convolutional network through chest radiography.

Lung-related ailments are prevalent all over the world which majorly includes asthma, chronic obstructive pulmonary disease (COPD), tuberculosis, pneumonia, fibrosis, etc. and now COVID-19 is added to this list. Infection of COVID-19 poses respirational complications with other indications like cough, high fever, and pneumonia. WHO had identified cancer in the lungs as a fatal cancer type amongst others and thus, the timely detection of such cancer is pivotal for an individual's health. Since the elementary convolutional neural networks have not performed fairly well in identifying atypical image types hence, we recommend a novel and completely automated framework with a deep learning approach for the recognition and classification of chronic pulmonary disorders (CPD) and COVID-pneumonia using Thoracic or Chest X-Ray (CXR) images. A novel three-step, completely automated, approach is presented that first extracts the region of interest from CXR images for preprocessing, and they are then used to detects infected lungs X-rays from the Normal ones. Thereafter, the infected lung images are further classified into COVID-pneumonia, pneumonia, and other chronic pulmonary disorders (OCPD), which might be utilized in the current scenario to help the radiologist in substantiating their diagnosis and in starting well in time treatment of these deadly lung diseases. And finally, highlight the regions in the CXR which are indicative of severe chronic pulmonary disorders like COVID-19 and pneumonia. A detailed investigation of various pivotal parameters based on several experimental outcomes are made here. This paper presents an approach that detects the Normal lung X-rays from infected ones and the infected lung images are further classified into COVID-pneumonia, pneumonia, and other chronic pulmonary disorders with an utmost accuracy of 96.8%. Several other collective performance measurements validate the superiority of the presented model. The proposed framework shows effective results in classifying lung images into Normal, COVID-pneumonia, pneumonia, and other chronic pulmonary disorders (OCPD). This framework can be effectively utilized in this current pandemic scenario to help the radiologist in substantiating their diagnosis and in starting well in time treatment of these deadly lung diseases.

Does climate knowledge act as a shield for farm livelihoods? Empirical analysis from the coastal and non-coastal ecosystems of India.

Developing countries with agrarian economy have been facing challenges arising from climate change events and its consequences. Climate knowledge influences the adaptation and mitigation measures shielding farm households in climatically vulnerable regions. Indian states with climatically vulnerable coastal and non-coastal agro-ecosystems have dominantly an agrarian economy; and small and marginal farmers' livelihoods are under focus through implementation of National Innovations in Climate Resilient Agriculture (NICRA) by the Indian Council of Agricultural Research. The present study was undertaken in one such state, Odisha. Climate knowledge test was developed following appropriate methods and administered to 200 farmers, 100 each in coastal and non-coastal NICRA districts to assess the knowledge level of dominant livelihood groups. Farmers' climate knowledge was higher in coastal district as compared to non-coastal district with overall climate knowledge index values of 53.10 and 43.95, respectively. Farmers who engaged in crop + livestock farming have better climate knowledge as compared to crop farmers and livestock farmers. Multiple regression and path analyses revealed social, economic, communication and psychological attributes of the farmers determining their climate knowledge level. Education level, social participation, participation in community initiatives, annual family income and personal cosmopolite information sources use are few such important determinants of climate knowledge. These dimensions require attention for the policy advocacies to improve climate knowledge so as to shield climatically vulnerable farm households.

Clinical outcomes and gestational age based prediction of pneumatosis intestinalis in preterm infants with necrotizing enterocolitis.

BACKGROUND: To determine the clinical implications and gestation age-specific diagnostic predictability of pneumatosis in preterm infants with necrotizing enterocolitis (NEC). METHODS: A retrospective study on abdominal radiographs comparing clinical and radiological information in infants with and without pneumatosis. RESULT: Our findings disproved our hypothesis. Pneumatosis was seen more frequently in infants with higher gestational age [28.4 (26.1-32.4) vs. 26.4 (24.3-29) weeks; p < 0.001] and birth weight [1110 (762-1768) vs. 770 (645-1022) grams; p < 0.001] and were more likely delivered vaginally (39.1% vs. 21.7%, p = 0.01). Portal venous gas was seen frequently on radiographs (10.3% vs. 0%, p < 0.001), but not pneumoperitoneum (20.7% vs. 36.7%, p = 0.02). Infants with pneumatosis frequently developed acute kidney injury, with higher serum creatinine (16.5% vs. 4.5%, p = 0.02) and frequent oliguria (12.9% vs. 2.7 %; p = 0.043) and had higher C-reactive protein levels at 24 and 96 hours (p < 0.002). Receiver operating curves for pneumatosis showed GA >28 weeks and birth weight > 1000 gm to have a sensitivity of 58.6% and specificity of 72.5%. CONCLUSION: Contrary to our hypothesis, infants who developed pneumatosis during NEC were more mature with a higher gestational age and birth weight than those who did not.