Efficacy of T piece resuscitator Versus self inflating bag and self inflating bag with peep valve in newborn resuscitation: A Randomised control trial

The American Academy of Paediatrics formulated the Neonatal resuscitation guidelines and published it in 2010 and suggested modification based on local needs1 .These guidelines primarily apply to neonates undergoing transition from intrauterine to extrauterine life with difficulty. About 1 in 10 neonates require some form of resuscitation and fewer than 1% require extensive resuscitation 2. Ventilation of the lungs is the most important step for successful resuscitation. Ineffective ventilation is an important cause of prolonged or unsuccessful resuscitation. Effective resuscitation needs proper anticipation, adequate preparation, accurate evaluation and prompt initiation. The first minute of neonatal resuscitation is known as the golden minute where active steps are taken to ventilate the newborn lungs. Each step in resuscitation is performed for 30 seconds along with assessment of heart rate, respiration and oxygen saturation at the end of every step. The decision to administer positive pressure ventilation (PPV) is taken at the end of 30 seconds of starting resuscitation when the neonate is apneic or gasping or with heart rate less than 100/min. 1. Use of T piece resuscitator resulted in higher number of neonates achieving a Heart rate _ 100/min at 2 minutes of age when compared to self inflating bag and self inflating bag with PEEP valve. Hence T piece resuscitator seems to be more effective than self inflating bag and self inflating bag with PEEP valve in delivery room newborn resuscitation of babies more than 28 weeks gestation. This was statistically insignificant. A larger sample size may be needed to clearly demonstrate the advantage of T piece resuscitator over self inflating bag and self inflating bag with PEEP valve. 2. Resuscitation with T piece resuscitator achieves a Heart rate _ 100 at a significantly lesser time than self inflating bag and self inflating bag with PEEP valve . 3. T piece resuscitator and self inflating bag with PEEP valve enables a newborn to achieve significantly higher oxygen saturation at 5 minutes of age than self inflating bag. The effect is more pronounced in more than 34 weeks gestational age. 4. T piece reduces the number of babies requiring delivery room intubation, chest compressions and medications compared to self inflating bag and self inflating bag with PEEP valve though statistically insignificant. 5. T piece resuscitator reduces the number of babies requiring invasive ventilation but the effect is not significant statistically. 6. There is no difference in complications like air leaks between the three devices. 7. Provision of PEEP by T piece resuscitator or self inflating bag with PEEP valve improves the short term outcomes in neonatal resuscitation but requires further adequately powered studies with higher sample size to test for statistical significance if any. 8. In settings where T piece resuscitator may not be available use of self inflating bag with PEEP valve could be an alternative resuscitation device in newborn resuscitation

Techno-Economic and Sustainable Challenges for EV Adoption in India: Analysis of the Impact of EV Usage Patterns and Policy Recommendations for Facilitating Seamless Integration

This paper explores the intricate challenges that are impeding the widespread adoption of Electric Vehicles (EVs) and explores the concerted efforts of the research community towards addressing these obstacles. The surge in interest surrounding EVs as a sustainable transportation alternative is undeniable, yet several hurdles persist in hindering their mass acceptance. From limitations in battery technology and charging infrastructure to concerns over range anxiety and manufacturing sustainability, these challenges form a multifaceted barrier. However, the research community has been actively engaged in tackling each issue with innovative solutions. Advancements in battery chemistry and energy storage, coupled with improvements in charging networks and smart grid integration, are poised to reshape the EV landscape. Moreover, studies on user behavior, public policy, and lifecycle analysis are contributing to the development of holistic strategies for enhancing EV adoption. By delving into these challenges and the ongoing research endeavors, this paper sheds light on the evolving pathway towards a future where EVs can thrive as a mainstream mode of transportation. Also, an analysis is conducted to evaluate the economic viability of EVs based on daily range considerations, with the objective of determining which category of users would benefit most from adopting EVs. Furthermore, policies are proposed that are aimed at establishing a harmonious and balanced EV ecosystem

Consumer Purchasing Decision towards Skin Care Products

The global trend of using skin care products is growing at accelerator rate. As a result of which number of skin care products are emerging as consumer options. The purpose of this study is to analyse the factors influencing consumers decision to purchase skin care products. The study is about the purchasing pattern of people in and around Coimbatore city. A self- designed questionnaire has been designed to collect the information from the respondent. Around 120 samples have been collected for this research. For identifying the purchasing behaviour of the consumer, the respondent was asked to rank the variables based on the Likert scale. The influence of social media on consumer behaviour is also analysed. The statistical analysis that has been done is regression. The insights gained will help the skin care marketers to develop the better growth strategy to sustain the market. This study provides the better understanding of how different variables influence purchasing behaviour

An open-label, 1-year extension study of the long-term safety and efficacy of once-daily OROS® hydromorphone in patients with chronic cancer pain

<p>Abstract</p> <p>Background</p> <p>Opioid analgesics have proven efficacy in the short-term management of chronic cancer pain, but data on their long-term use is more limited. OROS^®hydromorphone is a controlled-release formulation of oral hydromorphone that may be particularly well suited to long-term management of chronic cancer pain because it provides stable plasma concentrations and consistent analgesia with convenient once-daily dosing. The objective of this study (DO-118X) was to characterise the pain control achieved with long-term repeated dosing of OROS^®hydromorphone in patients with chronic cancer pain.</p> <p>Methods</p> <p>In this multicentre, phase III, open-label, single treatment, 1-year extension study, OROS^®hydromorphone was administered to 68 patients with moderate-to-severe chronic cancer pain, who had successfully completed a short-term equivalence study, and whose pain was controlled with a stable dose of medication (≥ 8 mg OROS^®hydromorphone or equivalent controlled-release morphine). Patients were started on the dose of OROS^®hydromorphone equivalent to the opioid dose on which they achieved dose-stable pain control in the equivalence study; dose adjustments were made as necessary and breakthrough pain medication was permitted. Efficacy was assessed with the Brief Pain Inventory (BPI) and patient and investigator global evaluations of treatment effectiveness. No formal statistical analysis was done.</p> <p>Results</p> <p>The mean (standard deviation) duration of exposure to study medication was 139 (129.9) days and the mean (standard deviation) average daily consumption of OROS^®hydromorphone was 43.7 (28.14) mg/day. All scores were maintained at a mild to moderate severity throughout the study; however, BPI scores for pain at its worst, pain at its least, pain on average, pain right now, and pain relief were slightly worsened at end point compared with baseline. Mean BPI pain interference with daily activities and patient and investigator global evaluation scores also remained generally stable. Treatment effectiveness was rated as fair to good throughout the study. The most frequently reported adverse events were nausea (n = 24, 35.3%), constipation (n = 22, 32.4%), and vomiting (n = 15, 22.1%).</p> <p>Conclusion</p> <p>The results of this extension study suggest that long-term repeated dosing with once-daily OROS^®hydromorphone can be beneficial in the continuing management of persistent, moderate-to-severe cancer pain.</p

Mir-21-Sox2 Axis Delineates Glioblastoma Subtypes with Prognostic Impact.

UNLABELLED: Glioblastoma (GBM) is the most aggressive human brain tumor. Although several molecular subtypes of GBM are recognized, a robust molecular prognostic marker has yet to be identified. Here, we report that the stemness regulator Sox2 is a new, clinically important target of microRNA-21 (miR-21) in GBM, with implications for prognosis. Using the MiR-21-Sox2 regulatory axis, approximately half of all GBM tumors present in the Cancer Genome Atlas (TCGA) and in-house patient databases can be mathematically classified into high miR-21/low Sox2 (Class A) or low miR-21/high Sox2 (Class B) subtypes. This classification reflects phenotypically and molecularly distinct characteristics and is not captured by existing classifications. Supporting the distinct nature of the subtypes, gene set enrichment analysis of the TCGA dataset predicted that Class A and Class B tumors were significantly involved in immune/inflammatory response and in chromosome organization and nervous system development, respectively. Patients with Class B tumors had longer overall survival than those with Class A tumors. Analysis of both databases indicated that the Class A/Class B classification is a better predictor of patient survival than currently used parameters. Further, manipulation of MiR-21-Sox2 levels in orthotopic mouse models supported the longer survival of the Class B subtype. The MiR-21-Sox2 association was also found in mouse neural stem cells and in the mouse brain at different developmental stages, suggesting a role in normal development. Therefore, this mechanism-based classification suggests the presence of two distinct populations of GBM patients with distinguishable phenotypic characteristics and clinical outcomes. SIGNIFICANCE STATEMENT: Molecular profiling-based classification of glioblastoma (GBM) into four subtypes has substantially increased our understanding of the biology of the disease and has pointed to the heterogeneous nature of GBM. However, this classification is not mechanism based and its prognostic value is limited. Here, we identify a new mechanism in GBM (the miR-21-Sox2 axis) that can classify ∼50% of patients into two subtypes with distinct molecular, radiological, and pathological characteristics. Importantly, this classification can predict patient survival better than the currently used parameters. Further, analysis of the miR-21-Sox2 relationship in mouse neural stem cells and in the mouse brain at different developmental stages indicates that miR-21 and Sox2 are predominantly expressed in mutually exclusive patterns, suggesting a role in normal neural development

The Mitochondrial Genome Is a “Genetic Sanctuary” during the Oncogenic Process

Since Otto Warburg linked mitochondrial physiology and oncogenesis in the 1930s, a number of studies have focused on the analysis of the genetic basis for the presence of aerobic glycolysis in cancer cells. However, little or no evidence exists today to indicate that mtDNA mutations are directly responsible for the initiation of tumor onset. Based on a model of gliomagenesis in the mouse, we aimed to explore whether or not mtDNA mutations are associated with the initiation of tumor formation, maintenance and aggressiveness. We reproduced the different molecular events that lead from tumor initiation to progression in the mouse glioma. In human gliomas, most of the genetic alterations that have been previously identified result in the aberrant activation of different signaling pathways and deregulation of the cell cycle. Our data indicates that mitochondrial dysfunction is associated with reactive oxygen species (ROS) generation, leading to increased nuclear DNA (nDNA) mutagenesis, but maintaining the integrity of the mitochondrial genome. In addition, mutational stability has been observed in entire mtDNA of human gliomas; this is in full agreement with the results obtained in the cancer mouse model. We use this model as a paradigm of oncogenic transformation due to the fact that mutations commonly found in gliomas appear to be the most common molecular alterations leading to tumor development in most types of human cancer. Our results indicate that the mtDNA genome is kept by the cell as a “genetic sanctuary” during tumor development in the mouse and humans. This is compatible with the hypothesis that the mtDNA molecule plays an essential role in the control of the cellular adaptive survival response to tumor-induced oxidative stress. The integrity of mtDNA seems to be a necessary element for responding to the increased ROS production associated with the oncogenic process

An Antagomir to MicroRNA Let7f Promotes Neuroprotection in an Ischemic Stroke Model

We previously showed that middle-aged female rats sustain a larger infarct following experimental stroke as compared to younger female rats, and paradoxically, estrogen treatment to the older group is neurotoxic. Plasma and brain insulin-like growth factor-1 (IGF-1) levels decrease with age. However, IGF-1 infusion following stroke, prevents estrogen neurotoxicity in middle-aged female rats. IGF1 is neuroprotective and well tolerated, but also has potentially undesirable side effects. We hypothesized that microRNAs (miRNAs) that target the IGF-1 signaling family for translation repression could be alternatively suppressed to promote IGF-1-like neuroprotection. Here, we report that two conserved IGF pathway regulatory microRNAs, Let7f and miR1, can be inhibited to mimic and even extend the neuroprotection afforded by IGF-1. Anti-mir1 treatment, as late as 4 hours following ischemia, significantly reduced cortical infarct volume in adult female rats, while anti-Let7 robustly reduced both cortical and striatal infarcts, and preserved sensorimotor function and interhemispheric neural integration. No neuroprotection was observed in animals treated with a brain specific miRNA unrelated to IGF-1 (anti-miR124). Remarkably, anti-Let7f was only effective in intact females but not males or ovariectomized females indicating that the gonadal steroid environment critically modifies miRNA action. Let7f is preferentially expressed in microglia in the ischemic hemisphere and confirmed in ex vivo cultures of microglia obtained from the cortex. While IGF-1 was undetectable in microglia harvested from the non-ischemic hemisphere, IGF-1 was expressed by microglia obtained from the ischemic cortex and was further elevated by anti-Let7f treatment. Collectively these data support a novel miRNA-based therapeutic strategy for neuroprotection following stroke

Genome-wide bidirectional CRISPR screens identify mucins as host factors modulating SARS-CoV-2 infection

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes a range of symptoms in infected individuals, from mild respiratory illness to acute respiratory distress syndrome. A systematic understanding of host factors influencing viral infection is critical to elucidate SARS-CoV-2–host interactions and the progression of Coronavirus disease 2019 (COVID-19). Here, we conducted genome-wide CRISPR knockout and activation screens in human lung epithelial cells with endogenous expression of the SARS-CoV-2 entry factors ACE2 and TMPRSS2. We uncovered proviral and antiviral factors across highly interconnected host pathways, including clathrin transport, inflammatory signaling, cell-cycle regulation, and transcriptional and epigenetic regulation. We further identified mucins, a family of high molecular weight glycoproteins, as a prominent viral restriction network that inhibits SARS-CoV-2 infection in vitro and in murine models. These mucins also inhibit infection of diverse respiratory viruses. This functional landscape of SARS-CoV-2 host factors provides a physiologically relevant starting point for new host-directed therapeutics and highlights airway mucins as a host defense mechanism

Beam dynamics corrections to the Run-1 measurement of the muon anomalous magnetic moment at Fermilab

This paper presents the beam dynamics systematic corrections and their uncertainties for the Run-1 data set of the Fermilab Muon g-2 Experiment. Two corrections to the measured muon precession frequency $\omega_a^m$ are associated with well-known effects owing to the use of electrostatic quadrupole (ESQ) vertical focusing in the storage ring. An average vertically oriented motional magnetic field is felt by relativistic muons passing transversely through the radial electric field components created by the ESQ system. The correction depends on the stored momentum distribution and the tunes of the ring, which has relatively weak vertical focusing. Vertical betatron motions imply that the muons do not orbit the ring in a plane exactly orthogonal to the vertical magnetic field direction. A correction is necessary to account for an average pitch angle associated with their trajectories. A third small correction is necessary because muons that escape the ring during the storage time are slightly biased in initial spin phase compared to the parent distribution. Finally, because two high-voltage resistors in the ESQ network had longer than designed RC time constants, the vertical and horizontal centroids and envelopes of the stored muon beam drifted slightly, but coherently, during each storage ring fill. This led to the discovery of an important phase-acceptance relationship that requires a correction. The sum of the corrections to $\omega_a^m$ is 0.50 $\pm$ 0.09 ppm; the uncertainty is small compared to the 0.43 ppm statistical precision of $\omega_a^m$