A Moderate Increase of Physiological CO2 in a Critical Range during Stable NREM Sleep Episode: A Potential Gateway to REM Sleep

Sleep is characterized as rapid eye movement (REM) and non-rapid eye movement (NREM) sleep. Studies suggest that wake-related neurons in the basal forebrain, posterior hypothalamus and brainstem, and NREM sleep-related neurons in the anterior-hypothalamic area inhibit each other, thus alternating sleep–wakefulness. Similarly, pontine REM-ON and REM-OFF neurons reciprocally inhibit each other for REM sleep modulation. It has been proposed that inhibition of locus coeruleus (LC) REM-OFF neurons is pre-requisite for REM sleep genesis, but it remains ambiguous how REM-OFF neurons are hyperpolarized at REM sleep onset. The frequency of breathing pattern remains high during wake, slows down during NREM sleep but further escalates during REM sleep. As a result, brain CO2 level increases during NREM sleep, which may alter REM sleep manifestation. It has been reported that hypocapnia decreases REM sleep while hypercapnia increases REM sleep periods. The groups of brainstem chemosensory neurons, including those present in LC, sense the alteration in CO2 level and respond accordingly. For example, one group of LC neurons depolarize while other hyperpolarize during hypercapnia. In another group, hypercapnia initially depolarizes but later hyperpolarizes LC neurons. Besides chemosensory functions, LC REM-OFF neurons are an integral part of REM sleep executive machinery. We reason that increased CO2 level during a stable NREM sleep period may hyperpolarize LC neurons including REM-OFF, which may help initiate REM sleep. We propose that REM sleep might act as a sentinel to help maintain normal CO2 level for unperturbed sleep

Investigation of complete and incomplete fusion in 7^{7}Li+124^{124}Sn reaction around Coulomb barrier energies

The complete and incomplete fusion cross sections for $^{7}$Li+$^{124}$Sn reaction were measured using online and offline characteristic $\gamma$-ray detection techniques. The complete fusion (CF) cross sections at energies above the Coulomb barrier were found to be suppressed by $\sim$ 26 \% compared to the coupled channel calculations. This suppression observed in complete fusion cross sections is found to be commensurate with the measured total incomplete fusion (ICF) cross sections. There is a distinct feature observed in the ICF cross sections, i.e., $\textit{t}$-capture is found to be dominant than $\alpha$-capture at all the measured energies. A simultaneous explanation of complete, incomplete and total fusion (TF) data was also obtained from the calculations based on Continuum Discretized Coupled Channel method with short range imaginary potentials. The cross section ratios of CF/TF and ICF/TF obtained from the data as well as the calculations showed the dominance of ICF at below barrier energies and CF at above barrier energies.Comment: 9 pages, 8 figure

Drug utilization pattern of antimicrobial agents in an outpatient department of otorhinolaryngology in a tertiary care hospital: a prospective, cross-sectional study

Background: Study based on antimicrobial drug utilization pattern and focus on factors related to prescribing, administering and its associated events. The aim of this study is to assess the prescribing patterns of antimicrobials, to assess the appropriateness of prescribed antimicrobials in an ear, nose and throat (ENT) infections.Methods: A prospective observational drug utilization study was carried out in otorhinolaryngology department for a period of 4 months. Patients who attended the ENT outpatient department (OPD) with ENT infections were included in the study and patients who were not willing to participate in the study were excluded and the data were analyzed.Results: Out of 155 patients, the average number of drugs per patient was 1.2. The percentage of drugs prescribed with the generic name was 26.32%. During this study, it was found that the most commonly prescribed groups of antimicrobials were penicillins (34.87%) followed by fluroqinolones (26.32%) and nitroimidazole (25%). During the study, it was observed that 46.71% patients visited for treating ear infections, 12.5% for nasal infections and 40.79% for throat infections. The routes of administration were oral (74.23%) and topical (20.10%).Conclusions: Our study shows some rational prescription patterns like less utilization of antimicrobials in ENT infections and were according to standard treatment guideline. The results of this study will be useful in future for making standard treatment guidelines. It also promotes the rational prescription and rational use of drugs

Training on an Appetitive (Delay)-Conditioning Task Enhances Oscillatory Waves During Sleep in the Cortical and Amygdalar Network

Oscillating waves during sleep play an essential role in memory consolidation. The cortical slow wave activity (SWA) and sigma waves during NREM sleep and theta waves during REM sleep increase after a variety of memory tasks including declarative, procedural and associative learning tasks. These oscillatory waves during sleep help to promote neural dialog between circuitries, which possibly plays a causal role in memory consolidation. However, the role of sleep-associated oscillating waves in a complex appetitive-conditioning paradigm is not clear. The parietal cortex and amygdala are involved in the cognitive evaluation of the environmental stimuli, and appetitive conditioning. Here, we have studied the changes in sleep architecture and oscillatory waves during NREM and REM sleep in the parietal cortices and amygdalar-local field potential (A-LFP) after appetitive-conditioning in the rat. We observed that REM sleep increased significantly after appetitive conditioning, which significantly positively correlated with performance on the appetitive-conditioning task. Further, the cortical SWA (0.1–4.5 Hz), and sigma (12–14.25 Hz) waves during NREM sleep, theta (6–9 Hz) waves during REM sleep, the amygdalar SWA (0.1–3.75 Hz) during NREM sleep and theta (6–8.25 Hz) waves during REM sleep significantly increased after appetitive conditioning. Interestingly, the augmented oscillatory waves significantly positively correlated with the performances on the appetitive-conditioning task. Our results suggest that the augmented REM sleep after conditioning may be required for the consolidation of appetitive-conditioned memory. Further, a significant correlation between augmented power in oscillatory waves during sleep and performance suggesting that these waves may be playing a crucial role in the consolidation of appetitive-conditioned memory

A Systematic Review Comparing the Play Profiles of Children with Special Health Care Needs with Typically Developing Children

Introduction. Although play has been used as a means to meet therapeutic goals by health care practitioners for a long time, there is a need to continuously review its conceptualisation and use in everyday practice to promote evidence-based practice. This systematic review aimed to evaluate the evidence on how the play of children with Special Health Care Needs (SHCN) is similar or different to that of typically developing children. Methods. Guided by the preferred reporting items for systematic reviews and meta-analyses (PRISMA) statement, we conducted a comprehensive review across five electronic databases for all studies that compared how the play of children with SHCN was similar or different to that of typically developing children. Data were extracted from the included studies, and methodological quality was assessed. Results. Eighteen studies met eligibility criteria. All the studies in this review were at risk of bias due to the study design. There was great variation in sample sizes, ranging between five and 112 participants in the diagnostic groups and five and 546 participants in control groups (typically developing children). The included studies investigated different aspects of play, which made it difficult to synthesise. However, of the 18 studies reviewed, thirteen reported that children with SHCN engage in less play, compared with typically developing children. Conclusions. Evidence supports the assumption that children with SHCN are less playful and spend less time engaging in play compared with typically developing children. This systematic review reveals paucity of research on play for children with several common chronic conditions such as HIV/AIDS, cancer, and cardiovascular diseases. Future studies need to reduce risks of bias, including the use of appropriate sample sizes, and must provide detailed results after investigating play in children with SHCN

Identifying the research, advocacy, policy and implementation needs for the prevention and management of respiratory syncytial virus lower respiratory tract infection in low- and middle-income countries

Introduction: The high burden of respiratory syncytial virus (RSV) infection in young children disproportionately occurs in low- and middle-income countries (LMICs). The PROUD (Preventing RespiratOry syncytial virUs in unDerdeveloped countries) Taskforce of 24 RSV worldwide experts assessed key needs for RSV prevention in LMICs, including vaccine and newer preventive measures. Methods: A global, survey-based study was undertaken in 2021. An online questionnaire was developed following three meetings of the Taskforce panellists wherein factors related to RSV infection, its prevention and management were identified using iterative questioning. Each factor was scored, by non-panellists interested in RSV, on a scale of zero (very-low-relevance) to 100 (very-high-relevance) within two scenarios: (1) Current and (2) Future expectations for RSV management. Results: Ninety questionnaires were completed: 70 by respondents (71.4% physicians; 27.1% researchers/scientists) from 16 LMICs and 20 from nine high-income (HI) countries (90.0% physicians; 5.0% researchers/scientists), as a reference group. Within LMICs, RSV awareness was perceived to be low, and management was not prioritised. Of the 100 factors scored, those related to improved diagnosis particularly access to affordable point-of-care diagnostics, disease burden data generation, clinical and general education, prompt access to new interventions, and engagement with policymakers/payers were identified of paramount importance. There was a strong need for clinical education and local data generation in the lowest economies, whereas upper-middle income countries were more closely aligned with HI countries in terms of current RSV service provision. Conclusion: Seven key actions for improving RSV prevention and management in LMICs are proposed

Genomics-assisted breeding in four major pulse crops of developing countries: present status and prospects

The global population is continuously increasing and is expected to reach nine billion by 2050. This huge population pressure will lead to severe shortage of food, natural resources and arable land. Such an alarming situation is most likely to arise in developing countries due to increase in the proportion of people suffering from protein and micronutrient malnutrition. Pulses being a primary and affordable source of proteins and minerals play a key role in alleviating the protein calorie malnutrition, micronutrient deficiencies and other undernourishment-related issues. Additionally, pulses are a vital source of livelihood generation for millions of resource-poor farmers practising agriculture in the semi-arid and sub-tropical regions. Limited success achieved through conventional breeding so far in most of the pulse crops will not be enough to feed the ever increasing population. In this context, genomics-assisted breeding (GAB) holds promise in enhancing the genetic gains. Though pulses have long been considered as orphan crops, recent advances in the area of pulse genomics are noteworthy, e.g. discovery of genome-wide genetic markers, high-throughput genotyping and sequencing platforms, high-density genetic linkage/QTL maps and, more importantly, the availability of whole-genome sequence. With genome sequence in hand, there is a great scope to apply genome-wide methods for trait mapping using association studies and to choose desirable genotypes via genomic selection. It is anticipated that GAB will speed up the progress of genetic improvement of pulses, leading to the rapid development of cultivars with higher yield, enhanced stress tolerance and wider adaptability

Global incidence, prevalence, years lived with disability (YLDs), disability-adjusted life-years (DALYs), and healthy life expectancy (HALE) for 371 diseases and injuries in 204 countries and territories and 811 subnational locations, 1990–2021: a systematic analysis for the Global Burden of Disease Study 2021

Background: Detailed, comprehensive, and timely reporting on population health by underlying causes of disability and premature death is crucial to understanding and responding to complex patterns of disease and injury burden over time and across age groups, sexes, and locations. The availability of disease burden estimates can promote evidence-based interventions that enable public health researchers, policy makers, and other professionals to implement strategies that can mitigate diseases. It can also facilitate more rigorous monitoring of progress towards national and international health targets, such as the Sustainable Development Goals. For three decades, the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) has filled that need. A global network of collaborators contributed to the production of GBD 2021 by providing, reviewing, and analysing all available data. GBD estimates are updated routinely with additional data and refined analytical methods. GBD 2021 presents, for the first time, estimates of health loss due to the COVID-19 pandemic. Methods: The GBD 2021 disease and injury burden analysis estimated years lived with disability (YLDs), years of life lost (YLLs), disability-adjusted life-years (DALYs), and healthy life expectancy (HALE) for 371 diseases and injuries using 100 983 data sources. Data were extracted from vital registration systems, verbal autopsies, censuses, household surveys, disease-specific registries, health service contact data, and other sources. YLDs were calculated by multiplying cause-age-sex-location-year-specific prevalence of sequelae by their respective disability weights, for each disease and injury. YLLs were calculated by multiplying cause-age-sex-location-year-specific deaths by the standard life expectancy at the age that death occurred. DALYs were calculated by summing YLDs and YLLs. HALE estimates were produced using YLDs per capita and age-specific mortality rates by location, age, sex, year, and cause. 95% uncertainty intervals (UIs) were generated for all final estimates as the 2·5th and 97·5th percentiles values of 500 draws. Uncertainty was propagated at each step of the estimation process. Counts and age-standardised rates were calculated globally, for seven super-regions, 21 regions, 204 countries and territories (including 21 countries with subnational locations), and 811 subnational locations, from 1990 to 2021. Here we report data for 2010 to 2021 to highlight trends in disease burden over the past decade and through the first 2 years of the COVID-19 pandemic. Findings: Global DALYs increased from 2·63 billion (95% UI 2·44–2·85) in 2010 to 2·88 billion (2·64–3·15) in 2021 for all causes combined. Much of this increase in the number of DALYs was due to population growth and ageing, as indicated by a decrease in global age-standardised all-cause DALY rates of 14·2% (95% UI 10·7–17·3) between 2010 and 2019. Notably, however, this decrease in rates reversed during the first 2 years of the COVID-19 pandemic, with increases in global age-standardised all-cause DALY rates since 2019 of 4·1% (1·8–6·3) in 2020 and 7·2% (4·7–10·0) in 2021. In 2021, COVID-19 was the leading cause of DALYs globally (212·0 million [198·0–234·5] DALYs), followed by ischaemic heart disease (188·3 million [176·7–198·3]), neonatal disorders (186·3 million [162·3–214·9]), and stroke (160·4 million [148·0–171·7]). However, notable health gains were seen among other leading communicable, maternal, neonatal, and nutritional (CMNN) diseases. Globally between 2010 and 2021, the age-standardised DALY rates for HIV/AIDS decreased by 47·8% (43·3–51·7) and for diarrhoeal diseases decreased by 47·0% (39·9–52·9). Non-communicable diseases contributed 1·73 billion (95% UI 1·54–1·94) DALYs in 2021, with a decrease in age-standardised DALY rates since 2010 of 6·4% (95% UI 3·5–9·5). Between 2010 and 2021, among the 25 leading Level 3 causes, age-standardised DALY rates increased most substantially for anxiety disorders (16·7% [14·0–19·8]), depressive disorders (16·4% [11·9–21·3]), and diabetes (14·0% [10·0–17·4]). Age-standardised DALY rates due to injuries decreased globally by 24·0% (20·7–27·2) between 2010 and 2021, although improvements were not uniform across locations, ages, and sexes. Globally, HALE at birth improved slightly, from 61·3 years (58·6–63·6) in 2010 to 62·2 years (59·4–64·7) in 2021. However, despite this overall increase, HALE decreased by 2·2% (1·6–2·9) between 2019 and 2021. Interpretation: Putting the COVID-19 pandemic in the context of a mutually exclusive and collectively exhaustive list of causes of health loss is crucial to understanding its impact and ensuring that health funding and policy address needs at both local and global levels through cost-effective and evidence-based interventions. A global epidemiological transition remains underway. Our findings suggest that prioritising non-communicable disease prevention and treatment policies, as well as strengthening health systems, continues to be crucially important. The progress on reducing the burden of CMNN diseases must not stall; although global trends are improving, the burden of CMNN diseases remains unacceptably high. Evidence-based interventions will help save the lives of young children and mothers and improve the overall health and economic conditions of societies across the world. Governments and multilateral organisations should prioritise pandemic preparedness planning alongside efforts to reduce the burden of diseases and injuries that will strain resources in the coming decades. Funding: Bill & Melinda Gates Foundation

Search for new particles in events with energetic jets and large missing transverse momentum in proton-proton collisions at root s=13 TeV

A search is presented for new particles produced at the LHC in proton-proton collisions at root s = 13 TeV, using events with energetic jets and large missing transverse momentum. The analysis is based on a data sample corresponding to an integrated luminosity of 101 fb(-1), collected in 2017-2018 with the CMS detector. Machine learning techniques are used to define separate categories for events with narrow jets from initial-state radiation and events with large-radius jets consistent with a hadronic decay of a W or Z boson. A statistical combination is made with an earlier search based on a data sample of 36 fb(-1), collected in 2016. No significant excess of events is observed with respect to the standard model background expectation determined from control samples in data. The results are interpreted in terms of limits on the branching fraction of an invisible decay of the Higgs boson, as well as constraints on simplified models of dark matter, on first-generation scalar leptoquarks decaying to quarks and neutrinos, and on models with large extra dimensions. Several of the new limits, specifically for spin-1 dark matter mediators, pseudoscalar mediators, colored mediators, and leptoquarks, are the most restrictive to date.Peer reviewe

Combined searches for the production of supersymmetric top quark partners in proton-proton collisions at root s=13 TeV

A combination of searches for top squark pair production using proton-proton collision data at a center-of-mass energy of 13 TeV at the CERN LHC, corresponding to an integrated luminosity of 137 fb(-1) collected by the CMS experiment, is presented. Signatures with at least 2 jets and large missing transverse momentum are categorized into events with 0, 1, or 2 leptons. New results for regions of parameter space where the kinematical properties of top squark pair production and top quark pair production are very similar are presented. Depending on themodel, the combined result excludes a top squarkmass up to 1325 GeV for amassless neutralino, and a neutralinomass up to 700 GeV for a top squarkmass of 1150 GeV. Top squarks with masses from 145 to 295 GeV, for neutralino masses from 0 to 100 GeV, with a mass difference between the top squark and the neutralino in a window of 30 GeV around the mass of the top quark, are excluded for the first time with CMS data. The results of theses searches are also interpreted in an alternative signal model of dark matter production via a spin-0 mediator in association with a top quark pair. Upper limits are set on the cross section for mediator particle masses of up to 420 GeV