Optic nerve sheath diameter as a non-invasive indicator of intracranial hypertension in traumatic brain injury: correlation with CT head and prognostic implications

Background: Ultrasound guided measurement of optic nerve sheath diameter (ONSD) is an emerging non invasive bedside tool that is being used to detect raised intracranial pressure (ICP) in patients with traumatic brain injury(TBI). Early detection of raised ICP can guide in the timely management of such patients with raised ICP due to TBI. Methods: A prospective, observational, open labelled study planned with a 30 patients of TBI of both genders, aged between 18 to 70 years. ONSD readings were taken 3 times a day for three days from the time of admission with portable SonoSite ultrasound machine. Data was expressed as mean ±standard deviation. Values were compared using T test and P value was calculated. Results: Highest reading recorded in patients with GCS <8 was 6.26±0.73 in comparison to 5.38±0.56 (p=0.001) in patients with GCS >8. Highest reading of ONSD  correlating  with a positive CT finding at admission was 6.22±.81 and was 5.46±.57 (p=0.006)  in patients with negative findings on CT. ROC curve with average cut off of 6 mm  correlated with positive CT findings with sensitivity of 80%, specificity of 70%  and negative predictive value of 87% was found. Conclusions: Ultrasound-guided ONSD monitoring shows promise for diagnosing intracranial hypertension in traumatic brain injury. Correlations with CT, GCS, and outcomes emphasize its clinical relevance, warranting further validatio

Study of Propanil Induced Toxicity on Heamatological Parameter and Amelioration by Taurine in Mice

This study was carried out to evaluate in vivo protective role of taurine on toxic effect caused by propanil in mice on the hematological values. Methods: In an experimental study 24 albino mice were distributed in six equal groups of six animals in each as follows

Text and Paintings

The manuscript now preserved as Indien 745 in the Manuscript Department of the Bibliothèque nationale de France (BnF) contains 137 paintings by an Indian artist, each accompanied by an explanation in French. These paintings depict deities and sages in static posture or narrative mode, as well as icons associated with temples. The present contribution forms a preliminary study of this manuscript in our project on South Indian manuscripts with paintings of deities preserved in the BnF

LARGE-SCALE POWER TRANSMISSION SYSTEMS' INTEGRATED ELECTRIC VEHICLE LOAD MODELLING

A variety of Electric Vehicle (EV) charging algorithms provide various EV charging load profiles, when utilized together, has an impact on the electrical grid functions. Present-day charging an EV Models of demand are either based on level of charging when an EV arrives or smart charging algorithms strengthened with specific charging levels and/or procedures. In this work, a brand-new data-driven technique for calculating EV charging load is suggested. They start by introducing a mathematical model that describes an adaptability of demand for EV charging. The characteristics of several EV load models are then identified, and advanced simulation techniques are suggested to simulate EV charging demand under various power market realizations. The suggested EV load modeling technique may act as a benchmark system by simulating various EV operating schedules, charging levels, and consumer engagement. The suggested framework would also give EV charging infrastructure advice from transmission system operators development in contemporary power networks

Reconstruction of diaminopimelic acid biosynthesis allows characterisation of Mycobacterium tuberculosis N-succinyl-L,L-diaminopimelic acid desuccinylase

With the increased incidence of tuberculosis (TB) caused by Mycobacterium tuberculosis there is an urgent need for new and better anti-tubercular drugs. N-succinyl-L,L-diaminopimelic acid desuccinylase (DapE) is a key enzyme in the succinylase pathway for the biosynthesis of meso-diaminopimelic acid (meso-DAP) and L-lysine. DapE is a zinc containing metallohydrolase which hydrolyses N-succinyl L,L diaminopimelic acid (L,L-NSDAP) to L,L-diaminopimelic acid (L,L-DAP) and succinate. M. tuberculosis DapE (MtDapE) was cloned, over-expressed and purified as an N-terminal hexahistidine ((His)6) tagged fusion containing one zinc ion per DapE monomer. We redesigned the DAP synthetic pathway to generate L,L-NSDAP and other L,L-NSDAP derivatives and have characterised MtDapE with these substrates. In contrast to its other Gram negative homologues, the MtDapE was insensitive to inhibition by L-captopril which we show is consistent with novel mycobacterial alterations in the binding site of this drug

Where To From Here? The Potential for Climate Change-Related Migration: What is the State of the International Approach to the Potential Problem of Climate Change-Related Migration, and what Contribution does Hodgkinson, Anderson, Burton and Young's Proposed Climate Change Displaced Persons Convention Make to the International Approach?

Climate change may be a relatively new phenomenon, but its effects are being felt throughout the world and having a significant impact on peoples’ lives in many countries. Some of those most keenly feeling the effects live in areas that are particularly vulnerable to destabilizing factors acting in conjunction with existing challenges. The effects of climate change are an exacerbating factor in sometimes already difficult lives. In some areas, the effects of climate change are or may become such that the inhabitants contemplate migration to find a more viable life elsewhere, either in their own country or in another country. It is by no means guaranteed that the effects of climate change will inexorably lead people, such as those in low-lying small island states, to migrate outside their country, particularly if there are adequate measures taken to mitigate and adapt to the effects of climate change. However, it is becoming increasingly clear that the potential for climate change-related migration is drawing near, if it has not already arrived, as a factor for some people’s decisions to migrate internally or externally. Some work currently underway considers approaches to dealing with climate change-related migration and the possible related issues around human rights protections and practical management. Climate change is an amorphous, complex and politically challenging issue for governments and stakeholders to deal with. Its effects on peoples’ lives can be significant, especially in conjunction with existing development, environmental, and economic challenges. It is important to ensure that any approach created is necessary, in light of existing mechanisms and available resources, and that it does not disadvantage any other groups of people through its creation or functioning. This thesis considers the state of the international approach to the potential problem of climate change-related migration. One recently developed approach was a proposed Climate Change Displaced Persons Convention, which has been formulated by Hodgkinson, Burton, Anderson and Young (2010). A range of information was considered to try and find a balance between the attempt to deal with climate change as a public and foreign policy issue and the human reactions and subsequent choices people make in dealing with the effects of climate change. Due to the complications of holding a position as a public servant working in the field of responses to climate change, I decided to use a methodology that would enable me to remain a step removed from the process, to avoid influencing responses. The thesis reviews current literature and experiences on climate change and migration, particularly in the Pacific, identifies key issues, and assesses the potential effectiveness of the Convention in addressing the issues identified. Information sources included drawing on reports of first hand experience of climate change related migration and those living in the front line on the islands, experiences of working in the public and NGO sectors, and academic considerations of how to address climate change and migration

Prophylactic and Therapeutic Potential of Asp f1 Epitopes in Naïve and Sensitized BALB/c Mice

Background: The present study examines a hypothesis that short allergen-derived peptides may shift an Aspergillus fumigatus (Afu-) specific TH2 response towards a protective TH1. Five overlapping peptides (P1-P5) derived from Asp f1, a major allergen/antigen of Afu, were evaluated for prophylactic or therapeutic efficacy in BALB/c mice. Methods: To evaluate the prophylactic efficacy, peptides were intranasally administered to naïve mice and challenged with Afu-allergens/antigens. For evaluation of therapeutic efficacy, the mice were sensitized with Afu-allergens/antigens followed by intranasal administration of peptides. The groups were compared for the levels of Afu-specific antibodies in sera and splenic cytokines evaluated by ELISA. Eosinophil peroxidase activity was examined in the lung cell suspensions and lung inflammation was assessed by histopathogy. Results; Peptides P1-, P2- and P3 decreased Afu-specific IgE (84.5~98.9%) and IgG antibodies (45.7~71.6%) in comparison with Afu-sensitized mice prophylactically. P1- and P2-treated ABPA mice showed decline in Afu-specific IgE (76.4~88%) and IgG antibodies (15~54%). Increased IgG2a/IgG1 and IFN-γ/IL-4 ratios were observed. P1-P3 prophylactically and P1 therapeutically decreased IL-5 levels and eosinophil peroxidase activity. P1 decreased inflammatory cells' infiltration in lung tissue comparable to non-challenged control. Conclusion: Asp f1-derived peptide P1, prophylactically and therapeutically administered to Balb/c mice, is effective in regulating allergic response to allergens/antigens of Afu, and may be explored for immunotherapy of allergic aspergillosis in humans

Multiomics Characterization of Preterm Birth in Low- and Middle-Income Countries.

Importance: Worldwide, preterm birth (PTB) is the single largest cause of deaths in the perinatal and neonatal period and is associated with increased morbidity in young children. The cause of PTB is multifactorial, and the development of generalizable biological models may enable early detection and guide therapeutic studies. Objective: To investigate the ability of transcriptomics and proteomics profiling of plasma and metabolomics analysis of urine to identify early biological measurements associated with PTB. Design, Setting, and Participants: This diagnostic/prognostic study analyzed plasma and urine samples collected from May 2014 to June 2017 from pregnant women in 5 biorepository cohorts in low- and middle-income countries (LMICs; ie, Matlab, Bangladesh; Lusaka, Zambia; Sylhet, Bangladesh; Karachi, Pakistan; and Pemba, Tanzania). These cohorts were established to study maternal and fetal outcomes and were supported by the Alliance for Maternal and Newborn Health Improvement and the Global Alliance to Prevent Prematurity and Stillbirth biorepositories. Data were analyzed from December 2018 to July 2019. Exposures: Blood and urine specimens that were collected early during pregnancy (median sampling time of 13.6 weeks of gestation, according to ultrasonography) were processed, stored, and shipped to the laboratories under uniform protocols. Plasma samples were assayed for targeted measurement of proteins and untargeted cell-free ribonucleic acid profiling; urine samples were assayed for metabolites. Main Outcomes and Measures: The PTB phenotype was defined as the delivery of a live infant before completing 37 weeks of gestation. Results: Of the 81 pregnant women included in this study, 39 had PTBs (48.1%) and 42 had term pregnancies (51.9%) (mean [SD] age of 24.8 [5.3] years). Univariate analysis demonstrated functional biological differences across the 5 cohorts. A cohort-adjusted machine learning algorithm was applied to each biological data set, and then a higher-level machine learning modeling combined the results into a final integrative model. The integrated model was more accurate, with an area under the receiver operating characteristic curve (AUROC) of 0.83 (95% CI, 0.72-0.91) compared with the models derived for each independent biological modality (transcriptomics AUROC, 0.73 [95% CI, 0.61-0.83]; metabolomics AUROC, 0.59 [95% CI, 0.47-0.72]; and proteomics AUROC, 0.75 [95% CI, 0.64-0.85]). Primary features associated with PTB included an inflammatory module as well as a metabolomic module measured in urine associated with the glutamine and glutamate metabolism and valine, leucine, and isoleucine biosynthesis pathways. Conclusions and Relevance: This study found that, in LMICs and high PTB settings, major biological adaptations during term pregnancy follow a generalizable model and the predictive accuracy for PTB was augmented by combining various omics data sets, suggesting that PTB is a condition that manifests within multiple biological systems. These data sets, with machine learning partnerships, may be a key step in developing valuable predictive tests and intervention candidates for preventing PTB

The FANCM:p.Arg658* truncating variant is associated with risk of triple-negative breast cancer

Abstract: Breast cancer is a common disease partially caused by genetic risk factors. Germline pathogenic variants in DNA repair genes BRCA1, BRCA2, PALB2, ATM, and CHEK2 are associated with breast cancer risk. FANCM, which encodes for a DNA translocase, has been proposed as a breast cancer predisposition gene, with greater effects for the ER-negative and triple-negative breast cancer (TNBC) subtypes. We tested the three recurrent protein-truncating variants FANCM:p.Arg658*, p.Gln1701*, and p.Arg1931* for association with breast cancer risk in 67,112 cases, 53,766 controls, and 26,662 carriers of pathogenic variants of BRCA1 or BRCA2. These three variants were also studied functionally by measuring survival and chromosome fragility in FANCM−/− patient-derived immortalized fibroblasts treated with diepoxybutane or olaparib. We observed that FANCM:p.Arg658* was associated with increased risk of ER-negative disease and TNBC (OR = 2.44, P = 0.034 and OR = 3.79; P = 0.009, respectively). In a country-restricted analysis, we confirmed the associations detected for FANCM:p.Arg658* and found that also FANCM:p.Arg1931* was associated with ER-negative breast cancer risk (OR = 1.96; P = 0.006). The functional results indicated that all three variants were deleterious affecting cell survival and chromosome stability with FANCM:p.Arg658* causing more severe phenotypes. In conclusion, we confirmed that the two rare FANCM deleterious variants p.Arg658* and p.Arg1931* are risk factors for ER-negative and TNBC subtypes. Overall our data suggest that the effect of truncating variants on breast cancer risk may depend on their position in the gene. Cell sensitivity to olaparib exposure, identifies a possible therapeutic option to treat FANCM-associated tumors

Prediction of gestational age using urinary metabolites in term and preterm pregnancies.

Assessment of gestational age (GA) is key to provide optimal care during pregnancy. However, its accurate determination remains challenging in low- and middle-income countries, where access to obstetric ultrasound is limited. Hence, there is an urgent need to develop clinical approaches that allow accurate and inexpensive estimations of GA. We investigated the ability of urinary metabolites to predict GA at time of collection in a diverse multi-site cohort of healthy and pathological pregnancies (n = 99) using a broad-spectrum liquid chromatography coupled with mass spectrometry (LC-MS) platform. Our approach detected a myriad of steroid hormones and their derivatives including estrogens, progesterones, corticosteroids, and androgens which were associated with pregnancy progression. We developed a restricted model that predicted GA with high accuracy using three metabolites (rho = 0.87, RMSE = 1.58 weeks) that was validated in an independent cohort (n = 20). The predictions were more robust in pregnancies that went to term in comparison to pregnancies that ended prematurely. Overall, we demonstrated the feasibility of implementing urine metabolomics analysis in large-scale multi-site studies and report a predictive model of GA with a potential clinical value