Phytotoxic characterization of various fractions of Launaea procumbens

Allelopathic screening of various fractions of Launaea procumbens, collected from Wah Cantt (Punjab) Pakistan, was conceded to identify potent allelopathic fraction for future phytochemical analyses. For this purpose, radish root inhibition method was used to test allelopathic potential. Two different concentrations of 100 ppm and 1000 ppm of Launaea procumbens were used in this study. Methanolic and ethyl acetate fraction potently inhibited root and radical growth; comparative to other fractions, it might be due to the presence of bioactive allelochemicals. Based on this screening, both of these fractions were recommended for future bioassay guided isolation of allelochemicals.Key words: Launaea procumbens, radish seeds, root inhibition, Launaea procumbens methanolic fraction

Impact of meningitis on intelligence and development: A systematic review and meta-analysis

BACKGROUND: We undertook a systematic review and meta-analysis to address the question "what is the impact of meningitis on IQ and development." METHODS: Search: conducted using standardized search terms across Medline, PsychInfo and EMBASE to 06/2014. Eligibility: human studies of any infectious aetiology of meningitis reporting IQ or infant developmental age or stage outcomes. Quality: Centre for Evidence Based Medicine, Oxford, quality tools. Analysis: random effects meta-analysis by organism. RESULTS: 39 studies were included in the review, 34 providing data on IQ (2015 subjects) and 12 on developmental delay (382 subjects). Across all bacterial organisms, meningitis survivors had a mean IQ 5.50 (95% CI: -7.19, -3.80; I2 = 47%, p = 0.02) points lower than controls. IQ was significantly lower than controls for Neisseria meningitides (NM: 5 points) and Haemophilus influenzae b (Hib: 6 points) but not in viral meningitis, with only single studies included for Streptococcus pneumoniae (SP) and group B streptococcus (GBS). The pooled relative risk (RR) for low IQ (IQ<70) in survivors of bacterial meningitis compared with controls was 4.99 (95% CI: 3.17, 7.86) with no significant heterogeneity (I2 = 49%, p = 0.07). Developmental delay of approximately 0.5SD was reported in studies of bacterial meningitis but no delay in the only study of viral meningitis. CONCLUSIONS: We found moderate evidence that surviving bacterial meningitis has a deleterious impact on IQ and development but no evidence that viral meningitis had meaningful cognitive impacts. Survivors of bacterial meningitis should be routinely offered screening for cognitive deficits and developmental delay in addition to hearing loss

Structure and function of the type III pullulan hydrolase from Thermococcus kodakarensis

Pullulan-hydrolysing enzymes, more commonly known as debranching enzymes for starch and other polysaccharides, are of great interest and have been widely used in the starch-saccharification industry. Type III pullulan hydrolase from Thermococcus kodakarensis (TK-PUL) possesses both pullulanase and α-amylase activities. Until now, only two enzymes in this class, which are capable of hydrolysing both α-1,4- and α-1,6-glycosidic bonds in pullulan to produce a mixture of maltose, panose and maltotriose, have been described. TK-PUL shows highest activity in the temperature range 95–100°C and has a pH optimum in the range 3.5–4.2. Its unique ability to hydrolyse maltotriose into maltose and glucose has not been reported for other homologous enzymes. The crystal structure of TK-PUL has been determined at a resolution of 2.8 Å and represents the first analysis of a type III pullulan hydrolyse. The structure reveals that the last part of the N-terminal domain and the C-terminal domain are significantly different from homologous structures. In addition, the loop regions at the active-site end of the central catalytic domain are quite different. The enzyme has a well defined calcium-binding site and possesses a rare vicinal disulfide bridge. The thermostability of TK-PUL and its homologues may be attributable to several factors, including the increased content of salt bridges, helical segments, Pro, Arg and Tyr residues and the decreased content of serine

Assessment of COVID-19 as the underlying cause of death among children and young people aged 0 to 19 years in the US.

IMPORTANCE: COVID-19 was the underlying cause of death for more than 940 000 individuals in the US, including at least 1289 children and young people (CYP) aged 0 to 19 years, with at least 821 CYP deaths occurring in the 1-year period from August 1, 2021, to July 31, 2022. Because deaths among US CYP are rare, the mortality burden of COVID-19 in CYP is best understood in the context of all other causes of CYP death. OBJECTIVE: To determine whether COVID-19 is a leading (top 10) cause of death in CYP in the US. DESIGN, SETTING, AND PARTICIPANTS: This national population-level cross-sectional epidemiological analysis for the years 2019 to 2022 used data from the US Centers for Disease Control and Prevention Wide-Ranging Online Data for Epidemiologic Research (WONDER) database on underlying cause of death in the US to identify the ranking of COVID-19 relative to other causes of death among individuals aged 0 to 19 years. COVID-19 deaths were considered in 12-month periods between April 1, 2020, and August 31, 2022, compared with deaths from leading non-COVID-19 causes in 2019, 2020, and 2021. MAIN OUTCOMES AND MEASURES: Cause of death rankings by total number of deaths, crude rates per 100 000 population, and percentage of all causes of death, using the National Center for Health Statistics 113 Selected Causes of Death, for ages 0 to 19 and by age groupings (<1 year, 1-4 years, 5-9 years, 10-14 years, 15-19 years). RESULTS: There were 821 COVID-19 deaths among individuals aged 0 to 19 years during the study period, resulting in a crude death rate of 1.0 per 100 000 population overall; 4.3 per 100 000 for those younger than 1 year; 0.6 per 100 000 for those aged 1 to 4 years; 0.4 per 100 000 for those aged 5 to 9 years; 0.5 per 100 000 for those aged 10 to 14 years; and 1.8 per 100 000 for those aged 15 to 19 years. COVID-19 mortality in the time period of August 1, 2021, to July 31, 2022, was among the 10 leading causes of death in CYP aged 0 to 19 years in the US, ranking eighth among all causes of deaths, fifth in disease-related causes of deaths (excluding unintentional injuries, assault, and suicide), and first in deaths caused by infectious or respiratory diseases when compared with 2019. COVID-19 deaths constituted 2% of all causes of death in this age group. CONCLUSIONS AND RELEVANCE: The findings of this study suggest that COVID-19 was a leading cause of death in CYP. It caused substantially more deaths in CYP annually than any vaccine-preventable disease historically in the recent period before vaccines became available. Various factors, including underreporting and not accounting for COVID-19's role as a contributing cause of death from other diseases, mean that these estimates may understate the true mortality burden of COVID-19. The findings of this study underscore the public health relevance of COVID-19 to CYP. In the likely future context of sustained SARS-CoV-2 circulation, appropriate pharmaceutical and nonpharmaceutical interventions (eg, vaccines, ventilation, air cleaning) will continue to play an important role in limiting transmission of the virus and mitigating severe disease in CYP

Lessons learned and lessons missed: impact of the coronavirus disease 2019 (COVID-19) pandemic on all-cause mortality in 40 industrialised countries and US states prior to mass vaccination [version 2; peer review: 2 approved]

Background: Industrialised countries had varied responses to the COVID-19 pandemic, which may lead to different death tolls from COVID-19 and other diseases. Methods: We applied an ensemble of 16 Bayesian probabilistic models to vital statistics data to estimate the number of weekly deaths if the pandemic had not occurred for 40 industrialised countries and US states from mid-February 2020 through mid-February 2021. We subtracted these estimates from the actual number of deaths to calculate the impacts of the pandemic on all-cause mortality. Results: Over this year, there were 1,410,300 (95% credible interval 1,267,600-1,579,200) excess deaths in these countries, equivalent to a 15% (14-17) increase, and 141 (127-158) additional deaths per 100,000 people. In Iceland, Australia and New Zealand, mortality was lower than would be expected in the absence of the pandemic, while South Korea and Norway experienced no detectable change. The USA, Czechia, Slovakia and Poland experienced >20% higher mortality. Within the USA, Hawaii experienced no detectable change in mortality and Maine a 5% increase, contrasting with New Jersey, Arizona, Mississippi, Texas, California, Louisiana and New York which experienced >25% higher mortality. Mid-February to the end of May 2020 accounted for over half of excess deaths in Scotland, Spain, England and Wales, Canada, Sweden, Belgium, the Netherlands and Cyprus, whereas mid-September 2020 to mid-February 2021 accounted for >90% of excess deaths in Bulgaria, Croatia, Czechia, Hungary, Latvia, Montenegro, Poland, Slovakia and Slovenia. In USA, excess deaths in the northeast were driven mainly by the first wave, in southern and southwestern states by the summer wave, and in the northern plains by the post-September period. Conclusions: Prior to widespread vaccine-acquired immunity, minimising the overall death toll of the pandemic requires policies and non-pharmaceutical interventions that delay and reduce infections, effective treatments for infected patients, and mechanisms to continue routine health care

On the Importance of Countergradients for the Development of Retinotopy: Insights from a Generalised Gierer Model

During the development of the topographic map from vertebrate retina to superior colliculus (SC), EphA receptors are expressed in a gradient along the nasotemporal retinal axis. Their ligands, ephrin-As, are expressed in a gradient along the rostrocaudal axis of the SC. Countergradients of ephrin-As in the retina and EphAs in the SC are also expressed. Disruption of any of these gradients leads to mapping errors. Gierer's (1981) model, which uses well-matched pairs of gradients and countergradients to establish the mapping, can account for the formation of wild type maps, but not the double maps found in EphA knock-in experiments. I show that these maps can be explained by models, such as Gierer's (1983), which have gradients and no countergradients, together with a powerful compensatory mechanism that helps to distribute connections evenly over the target region. However, this type of model cannot explain mapping errors found when the countergradients are knocked out partially. I examine the relative importance of countergradients as against compensatory mechanisms by generalising Gierer's (1983) model so that the strength of compensation is adjustable. Either matching gradients and countergradients alone or poorly matching gradients and countergradients together with a strong compensatory mechanism are sufficient to establish an ordered mapping. With a weaker compensatory mechanism, gradients without countergradients lead to a poorer map, but the addition of countergradients improves the mapping. This model produces the double maps in simulated EphA knock-in experiments and a map consistent with the Math5 knock-out phenotype. Simulations of a set of phenotypes from the literature substantiate the finding that countergradients and compensation can be traded off against each other to give similar maps. I conclude that a successful model of retinotopy should contain countergradients and some form of compensation mechanism, but not in the strong form put forward by Gierer

Vitamin D receptor ChIP-seq in primary CD4+ cells: relationship to serum 25-hydroxyvitamin D levels and autoimmune disease

PMCID: PMC3710212This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited

Mortality in ST-segment elevation myocardial infarction patients without standard modifiable risk factors: A race disaggregated analysis.

Background: Individuals who present with STEMI without the standard cardiovascular risk factors (SMuRFs) of diabetes, hypercholesterolemia, hypertension, and smoking, coined SMuRF-less are not uncommon. Little is known about their outcomes as a cohort and how they differ by race. Methods & Results: We identified 431,615 admissions with STEMI in the National Inpatient Sample (NIS) database 2015-2018, including patients with ≥ 1 SMuRF (n = 369,870) and those who were SMuRF-less (n = 234,745). SMuRF-less patients presented at a similar age (median age 63y vs 63y), were less likely to be female (33.6 % vs 34.6 %) and were almost twice as likely to present as a cardiac arrest (13.7 % vs 7.0 %), than those with ≥ 1 SMuRFs. SMuRF-less patients were less frequently in receipt of ICA (71.3 % vs 83.8 %) and PCI (58.0 % vs 72.2 %) compared to those with ≥ 1 SMuRF. Our race disaggregated analysis showed ethnic minority SMuRF-less patients were less likely than White patients to receive ICA and PCI, which was most apparent in Black patients with reduced odds of ICA (OR: 0.47, 95 % CI: 0.43-0.52) and PCI (OR: 0.46, 95 % CI: 0.52-0.50). Similarly, in ethnic minority subgroups within the SMuRF-less cohort, mortality and MACCE were significantly higher than in White patients. This was most profound in Black patients with in-hospital mortality (OR: 1.90, 95 % CI: 1.72-2.09) and MACCE (OR: 1.63, 95 % CI: 1.49-1.78) compared to White patients. Conclusion: Ethnic Minority SMuRF-less patients were less likely than White SMuRF-less patients to receive ICA and PCI and had worse mortality outcomes

A randomised control crossover trial of a theory based intervention to improve sun-safe and healthy behaviours in construction workers:Study protocol

Abstract Background Exposure to sunlight can have both positive and negative health impacts. Excessive exposure to ultra-violet (UV) radiation from the sun can cause skin cancer, however insufficient exposure to sunlight has a detrimental effect on production of Vitamin D. In the construction industry there are onsite proactive behaviours for safety, but sun-safety remains a low priority. There is limited research on understanding the barriers to adopting sun-safe behaviours and the association this may have with Vitamin D production. This paper reports a protocol for an intervention study, using text messaging in combination with a supportive smartphone App. The intervention aims to both reduce UV exposure during months with higher UV levels and promote appropriate dietary changes to boost Vitamin D levels during months with low UV levels. Method/design Approximately 60 construction workers will be recruited across the United Kingdom. A randomised control crossover trial (RCCT) will be used to test the intervention, with randomisation at site level – i.e. participants will receive both the control (no text messages or supportive App support) and intervention (daily text messages and supportive App). Using the Theory of Planned Behaviour (TPB) the intervention focuses on supporting sun-safety and healthy dietary decisions in relation to Vitamin D intake. The intervention emphasises cultivating the perception of normative support in the workplace, increasing awareness of control and self-efficacy in taking sun-protective behaviours, making healthier eating choices to boost Vitamin D, and tackling stigmas attached to image and group norms. Each study epoch will last 21 days with intervention text messages delivered on workdays only. The supportive App will provide supplementary information about sun protective behaviours and healthy dietary choices. The primary outcome measure is 25-hydroxy-Vitamin D [25(OH)D] level (obtained using blood spot sampling), which will be taken pre and post control and intervention periods. Secondary outcome measures are two-fold, (1) using the TPB to detect changes in behaviour, and (2) quantifying UV exposure during the UK peak radiation season (April–September) using body-mounted UV sensors. Discussion This study will provide important information about the effectiveness of a technology-based intervention to promote sun-safety and healthy behaviours in outdoor construction workers. Trial registration ISRCTN15888934 retrospectively registered 15.01.2018