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Abstract Perceptual learning refers to any change in discrimination abilities as a result of practice, a fundamental process that improves the organism’s response to the external environment. Visual perceptual learning (vPL) is supposed to rely on functional rearrangements in brain circuity occurring at early stages of sensory processing, with a pivotal role for the primary visual cortex (V1). However, top-down inputs from higher-order visual areas (HVAs) have been suggested to play a key part in vPL, conveying information on attention, expectation and the precise nature of the perceptual task. A direct assessment of the possibility to modulate vPL by manipulating top-down activity in awake subjects is still missing. Here, we used a combination of chemogenetics, behavioral analysis and multichannel electrophysiological assessments to show a critical role in vPL acquisition and retention for neuronal activity in the latero-medial secondary visual cortex (LM), the prime source for top-down feedback projections reentering V1.

Abstract Introduction Three randomised controlled trials (RCTs) have demonstrated that first-line cryoballoon pulmonary vein isolation decreases atrial tachycardia in patients with symptomatic paroxysmal atrial fibrillation (PAF) compared with antiarrhythmic drugs (AADs). The aim of this study was to develop a cost-effectiveness model (CEM) for first-line cryoablation compared with first-line AADs for the treatment of PAF. The model used a Danish healthcare perspective. Methods Individual patient-level data from the Cryo-FIRST, STOP AF and EARLY-AF RCTs were used to parameterise the CEM. The model structure consisted of a hybrid decision tree (one-year time horizon) and a Markov model (40-year time horizon, with a three-month cycle length). Health-related quality of life was expressed in quality-adjusted life years (QALYs). Costs and benefits were discounted at 3% per year. Model outcomes were produced using probabilistic sensitivity analysis. Results First-line cryoablation is dominant, meaning it results in lower costs (-€2,663) and more QALYs (0.18) when compared to first-line AADs. First-line cryoablation also has a 99.96% probability of being cost-effective, at a cost-effectiveness threshold of €23,200 per QALY gained. Regardless of initial treatment, patients were expected to receive ∼ 1.2 ablation procedures over a lifetime horizon. Conclusion First-line cryoablation is both more effective and less costly (i.e. dominant), when compared with AADs for patients with symptomatic PAF in a Danish healthcare system.

Abstract Background Vaccination has been recommended as one of the most potent ways of controlling the mpox (formerly, monkeypox) outbreak, particularly among high-risk groups. Here, we evaluated the prevalence of mpox vaccine acceptance and uptake globally. Methods We searched multiple databases for peer-reviewed studies published in English from May 2022 to 25th November 2023 that evaluated mpox vaccine acceptance and/or uptake. We fit a random-effects model meta-analysis to calculate the pooled mpox vaccine acceptance and uptake rates, with their 95% confidence intervals (CI) across population outcomes. We performed subgroup analyses among the six World Health Organization (WHO) regions (Africa [AFR], Region of the Americas [AMR], South-East Asia Region [SEAR], European Region [EUR], Eastern Mediterranean Region [EMR], and the Western Pacific Region [WPR]), as well as among select population subgroups. Results Of the 2531 studies screened, 61 studies, with a cumulative sample size of 263,857 participants from 87 countries were eligible for inclusion. The overall vaccine acceptance and uptake rates were 59.7% and 30.9% globally. Acceptance and uptake rates among the LGBTQI+ community were 73.6% vs 39.8% globally, 60.9% vs. 37.1% in AMR, 80.9% vs. 50.0% in EUR, and 75.2% vs. 33.5% in WPR. Among PLHIV, vaccine acceptance and uptake rates were 66.4% vs. 35.7% globally, 64.0% vs. 33.9% in AMR, 65.1% vs. 27.0% in EUR, and 69.5% vs. 46.6% in WPR. Among healthcare workers, vaccination intention was 51.0% globally. Conclusions Tailored interventions are needed to bolster confidence in the mpox vaccine, maximize vaccine uptake, and increase vaccine access to close the gaps between acceptance and uptake especially among key populations residing in regions with low rates of acceptance and uptake.

Objectives. The identity of the place has an effect on citizens’ identities. The study presented aims to support the connection between slow violence, environmental injustice, and the use of visual sociology to deepen the experiences and relations of people in the surrounding environment. The target is a neighborhood called Tamburi in the city of Taranto, Apulia. Methods. After an initial focus group useful to know more about the context, 8 people residing in the target area took photos to understand how the environmental damage has slowly settled on every aspect of life in the neighborhood and to explore concepts like social memories, and socio-semiotic category. The contribution of a non-residing photojournalist was analyzed, in order to improve and complete observation techniques. Results. Tamburi, literally incorporated by the industry, is a place with a complex identity to the detriment of social life and the new generations’ well-being, accompanied by a correlated social and cultural unease as well as a feeling of abandonment and vindication. It is identified as a sacrifice area due to the high rate of pollutants in circulation, premature deaths, and contamination of the urban and vegetable elements present. Conclusions. Living in territories vulnerable to sacrifice translates into considering the existences therein underestimated. The visual method offers interesting insights into the possibilities of interpreting some phenomena. The images of the neighborhood are a negative stimulus that communicates feelings of fragility in the individual and collective memory and has an impact on the livability and attractiveness of places.

Abstract Background Sepsis is a life-threatening condition which may arise from infection in any organ system and requires early recognition and management. Healthcare professionals working in any specialty may need to manage patients with sepsis. Educating medical students about this condition may be an effective way to ensure all future doctors have sufficient ability to diagnose and treat septic patients. However, there is currently no consensus on what competencies medical students should achieve regarding sepsis recognition and treatment. This study aims to outline what sepsis-related competencies medical students should achieve by the end of their medical student training in both high or upper-middle incomes countries/regions and in low or lower-middle income countries/regions. Methods Two separate panels from high or upper-middle income and low or lower-middle income countries/regions participated in a Delphi method to suggest and rank sepsis competencies for medical students. Each panel consisted of 13–18 key stakeholders of medical education and doctors in specialties where sepsis is a common problem (both specialists and trainees). Panelists came from all continents, except Antarctica. Results The panels reached consensus on 38 essential sepsis competencies in low or lower-middle income countries/regions and 33 in high or upper-middle incomes countries/regions. These include competencies such as definition of sepsis and septic shock and urgency of antibiotic treatment. In the low or lower-middle income countries/regions group, consensus was also achieved for competencies ranked as very important, and was achieved in 4/5 competencies rated as moderately important. In the high or upper-middle incomes countries/regions group, consensus was achieved in 41/57 competencies rated as very important but only 6/11 competencies rated as moderately important. Conclusion Medical schools should consider developing curricula to address essential competencies, as a minimum, but also consider addressing competencies rated as very or moderately important.

Assessment of major browse feed resources and determine the chemical composition of selected browse feed resource in Korahay Zone, Somali Regional State, was the aim of this study. Kebeles and the household heads were selected purposively in study area. The samples of fresh leaves (800 g) of selected browse species were collected to determine chemical compositions. SPSS version 20 was used for data analysis. The feed related constraints were ranked and analyzed by the ranking index. The current result indicated that, total of 22 trees, 6 shrub, 4 bush and 6 herbaceous species used as feed for livestock in dry and/or wet season were identified in the study area. DM, OM, CP, NDF, ADF, ADL and Ash of Dobera glabra, Grewia bicolor, Boscia minimfolia, Prosopis juliflora, Acacia Senegal, Unidentified (Alankhayir), Unidentified (Geed chic) were determined in current laboratory analysis. DM, OM, CP, NDF, ADF, ADL and Ash of Dobera glabra was 92.8 %, 94.28 %, 14.4 %, 42.5 %, 26.9 %, 5.22 % and 5.73 % respectively. Finally, feed quality and quantity, drought, invasive species and ecological deterioration were identified as major constraints of feed resources in study area. Due to this, intervention and further study should be conducted to tackle existing feed and feed related issues.

Ensuring data security is an essential priority to be put forward once there will be a digital transmission between any two or more targeted audience. Hence, the objective of this paper was to propose a better data security model for a protective information exchange on the internet with steganographic and cryptographic algorithms. Three cryptographic symmetric key encryption algorithm (RC6, Rijndael and TwoFish) and four steganographic carrier object (Image, audio, text and video) were considered. Data obtained show that Rijndael (AES) takes less encipherment and decipherment time compare to RC6 and TwoFish in cryptographic symmetric key encryption algorithm, while image carrier achieves better Peak-Signal-to-Noise Ratio if related to audio, video and text steganography. This research suggests the use of Advanced Encryption Standard and image steganography for efficient information interchange on the internet.

Objective Cryoballoon ablation for pulmonary vein isolation is a time-efficient procedure that can alleviate stress on electrophysiology lab resources. This analysis modeled the impact of cryoballoon ablation on electrophysiology lab operation using data from Latin America. Methods Data from centers in Argentina, Mexico, Colombia, and Chile of the Cryo Global Registry were used as inputs for an electrophysiology lab efficiency simulation model. The model used the assumption that either two (today’s electrophysiology lab operations) or three (including electrophysiology lab operational changes) cryoballoon ablation procedures could be performed per day. The endpoints were the percentage of days that resulted in 1) overtime and 2) time left for an extra non-ablation electrophysiology procedure. Results Data from a total of 232 procedures from six Latin American centers were included in the analysis. The average electrophysiology lab occupancy time for all procedures in Latin America was 132 ± 62 minutes. In the Current Scenario (two procedures per day), 7.4% of simulated days resulted in overtime, and 81.4% had enough time for an extra electrophysiology procedure. In the Enhanced Productivity Scenario (three procedures per day), 16.4% of days used overtime, while 67.4% allowed time for an extra non-ablation electrophysiology procedure. Conclusions Using real-world, Latin American-specific data, we found that with operational changes, three ablation procedures could feasibly be performed daily, leaving time for an extra electrophysiology procedure on more than half of days. Thus, use of cryoballoon ablation is an effective tool to enhance electrophysiology lab efficiency in resource-constrained regions such as Latin America.

Strategies to mobilise natural killer (NK) cells against cancer include tumour-targeting antibodies, NK cell engagers (NKCEs) and the adoptive transfer of ex vivo expanded healthy donor-derived NK cells. Genetic and functional studies have revealed that expression of the activating killer immunoglobulin-like receptor KIR2DS2 is associated with enhanced function in NK cells from healthy donors and improved outcome in several different malignancies. The optimal strategy to leverage KIR2DS2+ NK cells therapeutically is however currently unclear. In this study, we therefore evaluated the response of KIR2DS2-expressing NK cells to activation against cancer with clinically relevant tumour-targeting antibodies and following ex vivo expansion. We identified that KIR2DS2high NK cells from patients with chronic lymphocytic leukaemia and hepatocellular carcinoma had enhanced activation in response to tumour-targeting antibodies compared to KIR2DS2- NK cells. However, the superior function of healthy donor derived KIR2DS2high NK cells was lost following ex vivo expansion which is required for adoptive transfer-based therapeutic strategies. These data provide evidence that targeting KIR2DS2 directly in cancer patients may allow for the utilisation of their enhanced effector function, however such activity may be lost following their ex vivo expansion.

A survey of the malaria vectors in an area is a critical component of an effective vector control strategy. This study aimed to investigate the malaria vectors in four communities of Southern Gombe, Northeastern Nigeria. A total of 3200 adult female Anopheles reared from larvae in the four communities from two Local Government Areas (LGAs) in Southern Gombe were identified. Anopheles pretoriensis were dominant 1662 (51.9%) followed by An. gambiae sl 868(27.1%), An. maculipalpis 267(8.3), An. rufipes 252(7.9) and An. coustani 10(0.3%), and the least were An. pharoensis 6(0.2%). The remaining 135(4.3%) were unidentified. Of the 262 An. gambiae sl identified by species-specific PCR method, 135(51.5%) were found to be An. coluzzi, 60(22.9%) An. gambiae and only 1(0.4%) was An. arabiensis whereas hybrid constitutes 16(6.1%). To determine significant differences in species composition, the results from the four study sites were pooled together. Anopheles pretoriensis was significantly different from all the other species identified (p = 0.9999). There was a significant difference between the number of species identified as An. coluzzi and An. arabiensis (p = 0.0025). But there was no significant difference between An. coluzzi and An. gambiae (p = 0.1212). The heterogeneity and sympatry of Anopheles species observed is a threat to malaria control as the secondary vectors have behaviour that evades the current vector control interventions. It is expedient to re-strategize the vector control interventions in the study area.

Livestock plays a significant role in the livelihood enhancement of the people, especially in rural areas. The requirement for dietary protein for people from the animal sources is expected to increase. However, due to problems of feed shortages and high costs of feed the livestock sector and its contribution to the country’s economy are threatened in many countries. To address this problem, exploration of alternative sources of cheap feed resources is imperative. Azolla is one of the cheapest feed resources grown in water bodies, mainly in tropical and sub-tropical countries. There are various species of Azolla used as a feed source for livestock. Azolla filiculoides, Azolla pinnata and Azolla microphylla are the main species of Azolla that contribute to livestock feed. Nutritionally, Azolla is a good source of amino acids, minerals, and vitamins. It is commonly used for feeding poultry, sheep, and goats, and dairy cattle. Azolla is used as a supplementary feed with other feed resources to increase feed intake, growth, egg production, and milk yield, as proven by many researches. Besides animal feeding, Azolla is also used for soil fertility improvement, bioremediation, compost making, and biogas production. Therefore, the production and utilization of Azolla in an appropriate, way particularly in wetland areas will contribute to improving livestock nutrition and productivity.

AbstractThe purpose of this study was to investigate the feeding patten of Labeobarbus intermedius at Ribb Reservoir (Lake Tana Sub-basin, Ethiopia). A total of 498 specimens were collected using gillnets. Of these, 302 (60.6%) fish had different foods, while 196 (39.4%) were empty. The fish were dissected, their stomachs were removed, and stomach contents were preserved in a 5% formalin solution. Frequency of occurrence, volumetric method, index of preponderance, and geometric importance index were used to study the feeding pattern. Detritus was the primary food, accounting for 61.6% of the guts by volume. Mud, zooplankton, and phytoplankton were the second most important food items comprising 24.4%, 3.9%, and 2.8% by volume respectively. Feeding pattern differed with the size classes of fish. The smallest fish (17.0 cm FL) majorly consumed detritus followed by mud. The importance of mud increases when the fish grows more except (>31.5 cm FL) size class. The proportions of food items of L. intermedius significantly varied with respect to the dry and wet seasons. Detritus and mud were mostly consumed in the dry season, contributing to 47.8% and 32.4% by volume, respectively. Detritus was the most preferred food item during the wet season, contributing 97.2% of the total guts and 75.6% by volume. Generally, L. intermedius feeding pattern depending on size classes and seasonal variations this may be linked to food availability in the reservoir.

Objectives The primary objective of this study was to describe the self-reported reproductive health of retired elite women’s footballers with specific reference to menstrual function, pregnancy and motherhood, contraceptive use and pelvic floor function.Methods An electronic survey was disseminated to women’s footballers (18 years or older) who had retired from elite football within 10 years of completing the survey.Results 69 respondents completed the survey (mean age 35.8 years, mean age at retirement 30.3 years). One-third of participants self-reported experiencing at least one episode of amenorrhoea (>3 months without menstruation) for reasons other than hormonal contraceptive use or pregnancy. Three participants (mean age of 41 years, range 30–54) reported having reached menopause at the time of the study. 54 (78.3%) participants were not using any form of contraception. 17 (24.6%) of the participants are mothers (range 1–3 children). 51 of the participants (73.9%) had never been pregnant, and the majority of those who had been pregnant (86.7%) became pregnant in less than 2 years following the onset of desire for pregnancy. Four of the retired players gave birth during their playing career, and the mean time to return to competitive matches following delivery was 22 weeks. The mean Pelvic Floor Distress Inventory-20 score for participants was 72.Conclusion These insights can be used to inform future efforts to promote positive reproductive health outcomes for current, former and future women’s footballers. Research efforts should focus on improving the understanding of how to effectively support women’s footballers in the perinatal period. Best practice guidelines on the use of menstrual cycle monitoring and pelvic health support would improve standards of care for women’s footballers. Stakeholders should consider gender-specific postretirement care for women’s footballers.

Abstract Background Circulating biomarkers of bone formation and resorption are widely used in exercise metabolism research, but their responses to exercise are not clear. This study aimed to quantify group responses and inter-individual variability of P1NP and β-CTX-1 after prolonged, continuous running (60–120 min at 65–75% V̇O2max) in young healthy adult males using individual participant data (IPD) meta-analysis. Methods The protocol was designed following PRISMA-IPD guidelines and was pre-registered on the Open Science Framework prior to implementation ( https://osf.io/y69nd ). Changes in P1NP and β-CTX-1 relative to baseline were measured during, immediately after, and in the hours and days following exercise. Typical hourly and daily variations were estimated from P1NP and β-CTX-1 changes relative to baseline in non-exercise (control) conditions. Group responses and inter-individual variability were quantified with estimates of the mean and standard deviation of the difference, and the proportion of participants exhibiting an increased response. Models were conducted within a Bayesian framework with random intercepts to account for systematic variation across studies. Results P1NP levels increased during and immediately after running, when the proportion of response was close to 100% (75% CrI: 99 to 100%). P1NP levels returned to baseline levels within 1 h and over the next 4 days, showing comparable mean and standard deviation of the difference with typical hourly (0.1 ± 7.6 ng·mL−1) and daily (− 0.4 ± 5.7 ng·mL−1) variation values. β-CTX-1 levels decreased during and up to 4 h after running with distributions comparable to typical hourly variation (− 0.13 ± 0.11 ng·mL−1). There was no evidence of changes in β-CTX-1 levels during the 4 days after the running bout, when distributions were also similar between the running data and typical daily variation (− 0.03 ± 0.10 ng·mL−1). Conclusion Transient increases in P1NP were likely biological artefacts (e.g., connective tissue leakage) and not reflective of bone formation. Comparable small decreases in β-CTX-1 identified in both control and running data, suggested that these changes were due to the markers’ circadian rhythm and not the running intervention. Hence, prolonged continuous treadmill running did not elicit bone responses, as determined by P1NP and β-CTX-1, in this population.

Abstract Background There has been little exploration of the effect of fragility fractures on patient perceptions of their age. The common assumption is that fractures “happen to old people”. In individuals with a fragility fracture, our objective was to explore the experience of feeling old after sustaining a fragility fracture. Methods A secondary analysis of data from 145 community-dwelling women and men participating in six qualitative primary studies was conducted relying on a phenomenological approach. Participants were English-speaking, 45 years and older, who had sustained a recent fragility fracture or reported a history of previous fragility fractures. Data for the analysis included direct statements about feeling old as well any discussions relevant to age post-fracture. Results We highlight two interpretations based on how individuals with a history of fragility fracture talked about age: (1) Participants described feeling old post-fracture. Several participants made explicit statements about being “old”. However, the majority of participants discussed experiences post-fracture that implied that they felt old and had resigned themselves to being old. This appeared to entail a shift in thinking and perception of self that was permanent and had become a part of their identity; and (2) Perceptions of increasing age after sustaining a fracture were reinforced by health care providers, family, and friends. Conclusions Our findings challenge the notion that fractures “happen to old people” and suggest that fractures can make people feel old. Careful consideration of how bone health messages are communicated to patients post-fracture by health care providers is warranted. (Word Count: 248)

Abstract Schwann cell tumors are the most common cancers of the peripheral nervous system and can arise in patients with neurofibromatosis type-1 (NF-1) or neurofibromatosis type-2 (NF-2). Functional interactions between NF1 and NF2 and broader mechanisms underlying malignant transformation of the Schwann lineage are unclear. Here we integrate bulk and single-cell genomics, biochemistry, and pharmacology across human samples, cell lines, and mouse allografts to identify cellular de-differentiation mechanisms driving malignant transformation and treatment resistance. We find DNA methylation groups of Schwann cell tumors can be distinguished by differentiation programs that correlate with response to the MEK inhibitor selumetinib. Functional genomic screening in NF1-mutant tumor cells reveals NF2 loss and PAK activation underlie selumetinib resistance, and we find that concurrent MEK and PAK inhibition is effective in vivo. These data support a de-differentiation paradigm underlying malignant transformation and treatment resistance of Schwann cell tumors and elucidate a functional link between NF1 and NF2.

Abstract Healthcare-associated infections (HCAIs) are a major cause of morbidity and mortality in critically ill children. Data from adult studies suggest Selective Decontamination of the Digestive tract (SDD) may reduce the incidence of HCAIs and improve survival. There are no data from randomised clinical trials in the paediatric setting. An open label, parallel group pilot cRCT and mixed-methods perspectives study was conducted in six paediatric intensive care units (PICUs) in England. Participants were children (> 37 weeks corrected gestational age, up to 16 years) requiring mechanical ventilation expected to last for at least 48 h. Sites undertook standard care for a period of 9 weeks and were randomised into 3 sites which continued standard care and 3 where SDD was incorporated into infection control practice for eligible children. Interviews and focus groups were conducted for parents and staff working in PICU. 434 children fulfilled eligibility criteria, of whom 368 (85%) were enrolled. This included 207 in the baseline phase (Period One) and 161 in the intervention period (Period Two). In sites delivering SDD, the majority (98%) of children received at least one dose of SDD and of these, 68% commenced within the first 6 h. Whilst admission swabs were collected in 91% of enrolled children, consent for the collection of additional swabs was low (44%). Recruited children were representative of the wider PICU population. Overall, 3.6 children/site/week were recruited compared with the potential recruitment rate for a definitive cRCT of 3 children/site/week, based on data from all UK PICUs. Parents (n = 65) and staff (n = 44) were supportive of the aims of the study, suggesting adaptations for a larger definitive trial including formulation and administration of SDD paste, approaches to consent and ecology monitoring. Stakeholders identified preferred clinical outcomes, focusing on complications of critical illness and quality-of-life. A definitive cRCT in SDD to prevent HCAIs in critically ill children is feasible but should include adaptations to ecology monitoring along with the dosing schedule and packaging into a paediatric specific format. A definitive study is supported by the findings with adaptations to ecology monitoring and SDD administration. Trial Registration: ISRCTN40310490 Registered 30/10/2020.

The valorization and dissolution of lignin using ionic liquids (ILs) is critical for developing sustainable biorefineries and a circular bioeconomy. This review aims to critically assess the current state of computational and machine learning methods for understanding and optimizing IL-based lignin dissolution and valorization processes reported since 2022. The paper examines various computational approaches, from quantum chemistry to machine learning, highlighting their strengths, limitations, and recent advances in predicting and optimizing lignin-IL interactions. Key themes include the challenges in accurately modeling lignin’s complex structure, the development of efficient screening methodologies for ionic liquids to enhance lignin dissolution and valorization processes, and the integration of machine learning with quantum calculations. These computational advances will drive progress in IL-based lignin valorization by providing deeper molecular-level insights and facilitating the rapid screening of novel IL-lignin systems.

In this study, we investigate the symmetry analysis and explicit solutions for the Estevez–Mansfield–Clarkson (EMC) equation. Our main objectives are to identify the Lie point symmetries of the EMC equation, construct an optimal system of one-dimensional subalgebras, and reduce the EMC equation to a set of ordinary differential equations (ODEs). We employ the Riccati–Bernoulli sub-ODE method (RBSODE) to solve these reduced ODEs and obtain explicit solutions for the EMC model. The obtained solutions are validated using numerical analyses, and corresponding figures are presented to illustrate the physical implications of the derived solutions.

IntroductionMany decarbonization technologies have the added co-benefit of reducing short-lived climate pollutants, such as particulate matter (PM), nitrogen oxides (NOx), and sulfur dioxide (SO2), creating a unique opportunity for identifying strategies that promote both climate change solutions and opportunities for air quality improvement. However, stakeholders and decision-makers may struggle to quantify how these co-benefits will impact public health for the communities most affected by industrial air pollution.MethodsTo address this problem, the LOCal Air Emissions Tracking Atlas (LOCAETA) fills a data availability and analysis gap by providing estimated air quality benefits from industrial decarbonization options, such as carbon capture and storage (CCS). These co-benefits are calculated using an algorithm that connects disparate datasets that separately report greenhouse gas emissions and other pollutants at U.S. industrial facilities.ResultsVersion 1.0 of LOCAETA displays the estimated primary PM2.5 emission reduction co-benefits from additional pretreatment equipment for CCS on industrial and power facilities across the state of Louisiana, as well as the potential for VOC and NH3 generation. The emission reductions are presented in the tool alongside facility pollutant emissions information and relevant air quality, environmental, demographic, and public health datasets, such as air toxics cancer risk, satellite and in situ pollutant measurements, and population vulnerability metrics.DiscussionLOCAETA enables regulators, policymakers, environmental justice communities, and industrial and commercial users to compare and contrast quantifiable public health benefits due to air quality impacts from various climate change mitigation strategies using a free and publicly-available tool. Additional pollutant reductions can be calculated using the same methodology and will be available in future versions of the tool.

Introduction Three recent randomised controlled trials have demonstrated that pulmonary vein isolation as an initial rhythm control strategy with cryoablation reduces atrial arrhythmia recurrence in patients with symptomatic paroxysmal atrial fibrillation (PAF) compared with antiarrhythmic drug (AAD) therapy. The aim of this study was to evaluate the cost-effectiveness of first-line cryoablation compared with first-line AADs for treating symptomatic PAF in an English National Health Service (NHS) setting.Methods Individual patient-level data from 703 participants with PAF enrolled into Cryo-FIRST (Catheter Cryoablation Versus Antiarrhythmic Drug as First-Line Therapy of Paroxysmal Atrial Fibrillation), STOP AF First (Cryoballoon Catheter Ablation in an Antiarrhythmic Drug Naive Paroxysmal Atrial Fibrillation) and EARLY-AF (Early Aggressive Invasive Intervention for Atrial Fibrillation) were used to derive the parameters applied in the cost-effectiveness model (CEM). The CEM comprised a hybrid decision tree and Markov structure. The decision tree had a 1-year time horizon and was used to inform the initial health state allocation in the first cycle of the Markov model (40-year time horizon; 3-month cycle length). Health benefits were expressed in quality-adjusted life years (QALYs). Costs and benefits were discounted at 3.5% per year. Model outcomes were generated using probabilistic sensitivity analysis.Results The results estimated that cryoablation would yield more QALYs (+0.17) and higher costs (+£641) per patient over a lifetime than AADs. This produced an incremental cost-effectiveness ratio of £3783 per QALY gained. Independent of initial treatment, individuals were expected to receive ~1.2 ablations over a lifetime. There was a 45% relative reduction in time spent in AF health states for those initially treated with cryoablation.Discussion AF rhythm control with first-line cryoablation is cost effective compared with first-line AADs in an English NHS setting.

This working paper reviews the research and development in genetic improvement and breeding strategies of Bonga, Menz, Afar and Horro sheep in Ethiopia. This review aims to provide structured information regarding the Ethiopian indigenous sheep breeds (Bonga, Afar, Menz, and Horro) breeding programs and its progress. Genetic diversity is an essential element for genetic improvement, preserving populations, evaluation and adapting to variable environmental situations. Sustainable breeding techniques and sensible use of indigenous breed have been developed as result of recent research approaches to the conservation of sheep genetic resources. However, there is still growing interest of the government and of farmers in different breeding program to improve indigenous sheep breeds. There is no comprehensive study showing the performance of indigenous sheep breeds (Bonga, Afar, Menz, and Horro) genetic improvement under different breeding program and its progress, both biological and economic, to substantiate the argument on the benefit of different breeding programs for smallholders farmers. Programs for the sheep breeds Menz, Afar, Horro, and Bonga have now been developed at the community level. The idea behind the nucleus breeding program is to develop elite breeding animals by gathering the finest male and female breeding participants from the population in one central location. The first stage in creating a breeding program is defining the breeding goals. Planning breeding programs requires a thorough grasp of the farmers' (beneficiaries') breeding goals and production objectives. Therefore, this review makes it evident that numerous instruments and techniques, including choice experiments, participatory rural assessment procedures, and rating animals from flocks, have been used to define and ascertain the breeding aim of Afar, Horro, Bonga and Menz sheep breeds in Ethiopia.

Potent partnerships among researchers, policymakers, and community members have potential to produce positive changes in communities on a range of topics, including behavioral health. The paper provides a brief illustrative review of such partnerships and then describes the development and evolution of one partnership in particular in Virginia. The origin of the partnership is traced, along with its founding vision, mission, and values. Some of its several projects are described, including (a) needs assessment for implementation of evidence-based programs (EBPs) pursuant to the Family First Prevention Services Act; (b) statewide fidelity monitoring of key EBPs; and (c) projects to synergize state investments in specific EBPs, like multisystemic therapy, functional family therapy, and high fidelity wraparound. The paper concludes with some themes around which the center has evolved to serve the state and its citizens more effectively.

The alteration of mosquito life cycle using larvicides is key in the control of diseases transmitted by mosquitoes. The residual and environmental effect of some of these synthetic larvicides has given an opportunity to search for a potent larvicide as an alternate control measure against mosquitoes. Aqueous and ethanol extracts of Cymbopogon citratus and Annona senegalensis were tested against the 3rd and 4th instar larvae of Culex quinquefasciatus using a conventional method described by World Health Organization. Analysis of the ethanol extract for phytochemicals revealed that alkaloids, flavonoids, saponins, steroids, tannins, terpenoids and glycosides were present in both species. Toxicity activities of these extracts were observed on the Cx. quinquefasciatus larvae with the ethanol extract more potent than the aqueous extract. Ethanol extract of A. senegalensis exhibited potent larvicidal activity than C. citratus where 100% mortality was recorded after 24 h in all the treatment concentrations. This therefore, revealed that ethanol extract is more toxic than the aqueous extract on Cx. quinquefasciatus larvae. This is further evident in the result obtained from LC50 and LC95, where ethanol extract had recorded lower concentrations (-2.7E+07 and 0.891 ppm) for C. citratus and A. senegalensis, respectively as compared to 2.669 and 6.656 ppm of aqueous extracts for C. citratus and A. senegalensis, respectively. Therefore, it is imperative for more researches to be conducted on isolation and purification of compounds that enable the plants confers larvicidal properties on insect pests. Also, sustainable use of such bio-pesticides should be encouraged in mosquito control practices.

Introduction: Oral soft lesions represent a diverse array of pathological conditions that necessitate precise and effective treatment. Laser-assisted excision has gained prominence due to its purported benefits in terms of reduced procedural time, decreased bleeding, and improved aesthetic outcomes. However, conventional excision remains a common practice. Materials and Methods: A total of 100 patients with clinically diagnosed oral soft lesions were enrolled in this prospective study. The patients were randomly divided into two groups: the laser-assisted excision group and the conventional excision group. Demographics, lesion characteristics, and medical histories were recorded for each patient. Procedural parameters such as operative time and intraoperative bleeding were meticulously documented. Results: The laser-assisted excision group exhibited a statistically significant reduction in procedural duration compared to the conventional excision group (P < 0.05), with mean operative times of 15.2 and 20.8 min, respectively. Intraoperative bleeding was significantly reduced in the laser-assisted group (P < 0.01), with an average blood loss of 15.7 ml, while the conventional excision group reported an average blood loss of 28.6 ml. Postoperative complications analysis demonstrated that the laser-assisted group had a lower incidence of wound infections (P < 0.05) compared to the conventional excision group (5% vs. 15%). Additionally, the laser-assisted group exhibited significantly reduced scarring (P < 0.01) as reported by both patients and clinicians. Patient satisfaction scores were consistently higher in the laser-assisted excision group, with 85% of patients reporting contentment with the procedure, in contrast to 65% in the conventional excision group. Conclusion: In light of the results obtained from this study, laser-assisted excision emerges as a favorable approach for the management of oral soft lesions.

Introducción: La prevalencia de infecciones periprotésicas luego de una artroplastia total de cadera primaria es aproximadamente del 2%. El objetivo de este estudio fue determinar si existen diferencias estadísticamente significativas entre la tasa de infecciones periprotésicas agudas ante una profilaxis antibiótica extendida (7 días) y una profilaxis antibiótica estándar (24 h). Materiales y Métodos: Se realizó un estudio clínico prospectivo, entre julio de 2021 y mayo de 2022, que incluyó a 28 adultos con fractura de cadera sometidos a una artroplastia primaria que recibieron profilaxis antibiótica con cefalosporinas de primera generación durante 7 días a quienes se comparó con 95 adultos con fracturas de cadera con una artroplastia primaria y profilaxis antibiótica de 24 h, extraídos de una base de datos secundaria del registro del hospital. Resultados: La tasa de infecciones periprotésicas agudas fue del 10,71% en el grupo con profilaxis extendida y del 17,89% en quienes recibieron profilaxis estándar, sin diferencias estadísticamente significativas (p = 0,36). Conclusiones: Si bien, según la bibliografía disponible, la prolongación de la profilaxis antibiótica puede ser una medida simple, segura y rentable para contrarrestar los factores no modificables del paciente y así reducir las infecciones periprotésicas; en este estudio, no se demostró que la profilaxis antibiótica extendida disminuya la tasa de infecciones periprotésicas agudas a los 30 días en pacientes con artroplastias de cadera primarias.

Successful malaria diagnosis is the mainstay of successful treatment, prevention and eradication of malaria infection. Apart from the gold standard technique (Microscopy), numerous diagnostic techniques perform a similar function to microscopy and in most cases tend to have varying sensitivity and specificity, especially when compared with the gold standard technique. Therefore this study aimed to determine the Performance and accuracy of SD Bioline Malaria Ag P.f (05fk50) (Rapid Diagnostic Test kit) to Gold standard (Microscopy). A total of two hundred (200) samples were collected from the consented study subjects and analyzed using RDT and Giemsa staining technique. The result revealed an overall prevalence of 132(66.0%) and 167(83.5%) respectively by RDT and Microscopy, where 115 (57.5%) were true positive, there was no significant difference between the two techniques (P> 0.05, df= 1, χ2 = 3.695). The RDT recorded a sensitivity and specificity value of 68.86% and 48.48% respectively with a positive predictive value of 87.78% and a negative predictive value of 23.53%. The RDT recorded an overall accuracy of 0.66. The Rapid Diagnostic test kit used in the present demonstrated a high level of sensitivity and positive predictive value with relatively low specificity and negative predictive value. Regular checks on the Performance and accuracy of all brands of RDT should be conducted as their perform

The idiom ‘more high-quality research is needed’ has become the slogan for sport and exercise physiology-based research in female athletes. However, in most instances, it is challenging to address this gap of high-quality research in elite female athletes at a single study site due to challenges in recruiting enough participants with numerous menstrual cycle and contraceptive pill permutations. Accordingly, we have assembled an international multisite team to undertake an innovative project for female athletes, which investigates the effects of changes in endogenous and exogenous oestrogen and progesterone/progestins across the menstrual cycle and in response to second-generation combined monophasic contraceptive pill use, on aspects of exercise physiology and athletic performance. This project will employ the current gold-standard methodologies in this area, resulting in an adequately powered dataset. This protocol paper describes the consortium-based approach we will undertake during this study.

Abstract Background There is no country in the developing world where iodine deficiency is not a public health problem including Ethiopia. Therefore, this study aimed to assess inadequate utilization of iodized salt and associated factors at household level in woreda 11 Nifas Silk Sub-city, Addis Ababa, Ethiopia. Methods A community-based cross-sectional study was conducted with multistage sampling technique on 348 household respondents. The data were collected using interviewer-administered structured questionnaires and an iodine rapid test kit. The data were edited, cleaned, and entered using Epi-data version 4.6.2 and exported to SPSS version 25 for analysis. A multivariable logistic regression model was fitted to identify associated factors for inadequate utilization of iodized salt. The statistical significance was declared at a p-value of less than 0.05 with 95% confidence interval. Results A total of 348 household respondents were participated. The amount of iodine content in salt 0 ppm, 15ppm were 11.8%, 7.2% and 81.0% respectively. Total inadequate utilization of iodized salt was 19%. Using unpacked salt [AOR; 0.50 (95%CI: 0.27, 0.93)], using a container without a lid [AOR; 0.29 (95%CI: 013, 0.63)], and having insufficient knowledge [AOR; 2.10 (95%CI: 1.14, 3.86)] were all significantly connected with using inadequate iodized salt. Conclusions Iodized salt utilization was inadequate. Using containers without a lid, unpacked salt, and poor knowledge were associated factors. There should be a provision of adequate knowledge about iodized salt, a proper storage and handling.

ABSTRACT Objective Recent studies have found that human Friedreich ataxia patients have dysfunction of transmission in the auditory neural pathways. Here, we characterize hearing deficits in a mouse model of Friedreich ataxia and compare these to a clinical population. Methods Sixteen mice with a C57BL/6 background were evaluated. Eight were YG8Pook/J animals (Friedreich ataxia phenotype) and eight wild‐type mice served as controls. Auditory function was assessed between ages 6 and 12 months using otoacoustic emissions and auditory steady‐state responses. At study end, motor deficit was assessed using Rotorod testing and inner ear tissue was examined. Thirty‐seven individuals with Friedreich ataxia underwent auditory steady‐state evoked potential assessment and response amplitudes were compared with functional hearing ability (speech perception‐in‐noise) and disease status was measured by the Friedreich Ataxia Rating Scale. Results The YG8Pook/J mice showed anatomic and functional abnormality. While otoacoustic emission responses from the cochlear hair cells were mildly affected, auditory steady‐state responses showed exaggerated amplitude reductions as the animals aged with Friedreich ataxia mice showing a 50–60% decrease compared to controls who showed only a 20–25% reduction (F(2,94) = 17.90, p

Background Healthcare-associated infections are a major cause of morbidity and mortality in critically ill children. In adults, data suggest the use of selective decontamination of the digestive tract may reduce the incidence of healthcare-associated infections. Selective decontamination of the digestive tract has not been evaluated in the paediatric intensive care unit population. Objectives To determine the feasibility of conducting a multicentre, cluster-randomised controlled trial in critically ill children comparing selective decontamination of the digestive tract with standard infection control. Design Parallel-group pilot cluster-randomised controlled trial with an integrated mixed-methods study. Setting Six paediatric intensive care units in England. Participants Children (> 37 weeks corrected gestational age, up to 16 years) requiring mechanical ventilation expected to last for at least 48 hours were eligible for the PICnIC pilot cluster-randomised controlled trial. During the ecology periods, all children admitted to the paediatric intensive care units were eligible. Parents/legal guardians of recruited patients and healthcare professionals working in paediatric intensive care units were eligible for inclusion in the mixed-methods study. Interventions The interventions in the PICnIC pilot cluster-randomised controlled trial included administration of selective decontamination of the digestive tract as oro-pharyngeal paste and as a suspension given by enteric tube during the period of mechanical ventilation. Main outcome measures The decision as to whether a definitive cluster-randomised controlled trial is feasible is based on multiple outcomes, including (but not limited to): (1) willingness and ability to recruit eligible patients; (2) adherence to the selective decontamination of the digestive tract intervention; (3) acceptability of the definitive cluster-randomised controlled trial; (4) estimation of recruitment rate; and (5) understanding of potential clinical and ecological outcome measures. Results A total of 368 children (85% of all those who were eligible) were enrolled in the PICnIC pilot cluster-randomised controlled trial across six paediatric intensive care units: 207 in the baseline phase (Period One) and 161 in the intervention period (Period Two). In sites delivering selective decontamination of the digestive tract, the majority (98%) of children received at least one dose of selective decontamination of the digestive tract, and of these, 68% commenced within the first 6 hours. Consent for the collection of additional swabs was low (44%), though data completeness for potential outcomes, including microbiology data from routine clinical swab testing, was excellent. Recruited children were representative of the wider paediatric intensive care unit population. Overall, 3.6 children/site/week were recruited compared with the potential recruitment rate for a definitive cluster-randomised controlled trial of 3 children/site/week, based on data from all UK paediatric intensive care units. The proposed trial, including consent and selective decontamination of the digestive tract, was acceptable to parents and staff with adaptations, including training to improve consent and communication, and adaptations to the administration protocol for the paste and ecology monitoring. Clinical outcomes that were considered important included duration of organ failure and hospital stay, healthcare-acquired infections and survival. Limitations The delivery of the pilot cluster-randomised controlled trial was disrupted by the COVID-19 pandemic, which led to slow set-up of sites, and a lack of face-to face training. Conclusions PICnIC’s findings indicate that a definitive cluster-randomised controlled trial in selective decontamination of the digestive tract in paediatric intensive care units is feasible with the inclusion modifications, which would need to be included in a definitive cluster-randomised controlled trial to ensure that the efficiency of trial processes is maximised. Future work A definitive trial that incorporates the protocol adaptations and outcomes arising from this study is feasible and should be conducted. Trial registration This trial is registered as ISRCTN40310490. Funding This award was funded by the National Institute for Health and Care Research (NIHR) Health Technology Assessment programme (NIHR award ref: 16/152/01) and is published in full in Health Technology Assessment; Vol. 28, No. 8. See the NIHR Funding and Awards website for further award information. Plain language summary Each year, around 20,000 critically ill children are admitted to paediatric intensive care units in the UK. These children are at a higher risk of healthcare-associated infections, one of the main sources of which is the large number of bacteria in the digestive tract. Spread of bacteria from the digestive tract into other organs, such as the lung (causing ventilator-associated pneumonia) or bloodstream (causing sepsis), can be life-threatening. The risk is highest in those children whose illness is so severe that they require prolonged mechanical ventilation. Stopping the growth of bacteria in the digestive tract (called selective decontamination of the digestive tract) has been shown in adults to reduce the number of hospital-acquired infections. However, there have been no trials in children. We wanted to assess how practical and acceptable such a trial would be comparing standard infection control to selective decontamination of the digestive tract-enhanced infection control and monitoring how each intervention affected antimicrobial resistance. We undertook a pilot study to examine whether clinicians could identify eligible children, enrol them in the study and follow study procedures during the course of paediatric intensive care unit admission. Alongside this, we interviewed parents and clinicians to get their views on the proposed trial. Six hospitals recruited 559 patients over a period of roughly 7 months. Hospitals were randomly allocated to continue with the standard infection control procedure or to give selective decontamination of the digestive tract. Overall, recruitment was higher than expected. Alongside this, we examined the views of patients, caregivers and healthcare professionals to assess their views on whether a trial should be carried out to see if selective decontamination of the digestive tract should become part of the infection control regime for children most at risk of hospital-acquired infection in the paediatric intensive care unit. Overall results suggest that a larger PICnIC trial incorporating patient stakeholder and clinical staff feedback on design and outcomes is feasible and that it is appropriate to conduct a trial into the effectiveness of selective decontamination of the digestive tract administration to minimise hospital-acquired infections. Scientific summary Background In critically ill children, healthcare-associated infections (HCAIs) are a major cause of morbidity and mortality, with a reported incidence of 7–14%. In this vulnerable population, contributing factors include the impact of critical illness on innate and adaptive immune responses, as well as the presence of invasive devices such as endotracheal tubes, urinary catheters and vascular lines. Evidence from adult intensive care studies suggests that using selective decontamination of the digestive tract (SDD) alongside standard infection control measures reduces mortality and ventilator-associated pneumonia (VAP). A recent meta-analysis of 32 randomised controlled trials (RCTs) including 24,389 participants suggests that use of SDD compared with standard care or placebo was associated with reduced hospital mortality, VAP and intensive care unit (ICU)-acquired bacteraemia. Selective decontamination of the digestive tract has not been compared directly with modern infection control protocols in the paediatric intensive care unit (PICU) population. Infection Control in Paediatric Intensive Care (PICnIC) was a feasibility study designed to determine whether it is possible to conduct a cluster RCT (cRCT) of SDD in critically ill children expected to require mechanical ventilation for over 48 hours, and to explore and test the acceptability of key components of the study to healthcare professionals and caregivers. The study involved a pilot cRCT with an integrated mixed-methods study. Infection Control in Paediatric Intensive Care pilot cluster-randomised controlled trial Objectives To test the ability to randomise PICUs to either control or intervention. To test the willingness and ability of healthcare professionals to screen and recruit eligible children. To estimate the recruitment rate of eligible children. To test adherence to the SDD protocol. To test the procedures for assessing and collecting selected clinical and ecological outcomes and for adverse event (AE) reporting. To assess the generalisability of the study results to all PICUs using the Paediatric Intensive Care Audit Network (PICANet). To explore parent and healthcare professional views on the acceptability of the proposed trial, including recruitment and consent procedures and patient-centred outcomes. Methods Study design Multicentre pilot cRCT. Sites Six PICUs in the UK. Recruitment A research without prior consent (RWPC) model was used, and retrospective consent sought for additional samples. There were no inclusion/exclusion criteria during ecology weeks. During Periods One and Two, the eligibility criteria were the following: Inclusion criteria > 37 weeks corrected gestational age to 16 years. Receiving mechanical ventilation. Expected to remain on mechanical ventilation for ≥ 48 hours (from time of screening). Exclusion criteria Known allergy, sensitivity or interaction to polymyxin E (colistin), tobramycin or nystatin. Known to be pregnant. Death perceived as imminent. Randomisation Participating PICUs were randomised by the trial statistician using computer-based randomisation to either the control or intervention arm for Period Two of the study. Data collection A secure, dedicated electronic case report form (eCRF) was set up and collection was nested within PICANet. Sample size A sample size of 324 children in 18 weeks was anticipated. A power calculation was deemed not appropriate given the feasibility nature of the study. The sample size was therefore determined on expected eligible caseload based on available data from PICANet. Data analysis The analyses were conducted using Stata/MP™ version 16.1 (StataCorp LP, College Station, TX, USA). Results As planned, six sites participated in the PICnIC pilot cRCT and were randomised in week 6. We confirmed the willingness and ability of healthcare professionals to screen and recruit eligible children. Sites recruited a total of 368 children (85% of all those who were eligible) across six sites: in Period One, 207 children were recruited (93% of those who were eligible), and in Period Two, 161 children were recruited (76% of those who were eligible). All intervention sites delivered SDD during week 12 onwards. We defined the recruitment rate of eligible children. Overall, 3.6 children/site/week were recruited (the recruitment rate for Period One was 4.3 children/site/week; for Period Two, this was 3.0 children/site/week), similar to the average pre-trial estimate of 3 children/site/week. The potential recruitment rate for a future definitive cRCT trial is 2.98 children/site/week, based on a potentially eligible population of 1730 children (national UK PICU data from PICANet) and the overall proportion of eligible children recruited (85%). We confirmed the ability of healthcare professionals to adhere to the SDD protocol. The majority of children eligible for inclusion were recruited in the intervention sites (55/57, 98%) and most (68%) received at least one dose of SDD treatment within the first 6 hours of enrolment. The median number of SDD doses administered per patient was 14 [interquartile range (IQR) 9–32] for the Oral Paste and 14 (IQR 9–32) for Gastric Suspension. The number of missed doses was low: 9.2% for the oral paste and 9.1% for the gastric suspension. Reasons included children being nil by mouth (29.5% and 31.1% for oral paste and gastric suspensions, respectively) and dose missed by clinicians (26.2% and 24.6%). We confirmed that procedures for assessing and collecting selected clinical and ecological outcomes and for AE reporting were adequate. Completeness of the ecology outcome measures was excellent in intervention sites (range between 97.6% and 100%) and very good in the usual care sites (range between 93.1% and 100%). Patient-centred potential outcomes measures had an excellent completion rate and were similar between groups with a range between 96.3% and 100%. Ecological outcomes had high completion rates and were similar between groups. Consent for the collection of additional samples for study-specific ecology monitoring were obtained in 162 patients (44% of those recruited). Over 30% of the recruited patients were deemed unable to approach for consent. We confirmed the generalisability of the study results to all PICUs using the PICANet. Children who were recruited to the PICnIC study were representative of similar potentially eligible patients in the study PICUs and all UK PICUs but were more likely to be male (62% vs. 56%) and with a primary diagnosis of infection (12.8% vs. 7%) when compared with all UK PICUs. Infection Control in Paediatric Intensive Care mixed-methods study Objectives To assess with input from PICU healthcare professionals: the acceptability of implementation of the SDD intervention, recruitment and consent procedures the acceptability of collecting data to assess the selected clinical and ecological data the acceptability of the SDD intervention and confirm interest in participation in a definitive trial in the wider PICU community. To review, explore and test with input from parents/guardians of recruited patients: the acceptability of a definitive trial that includes the SDD intervention the acceptability of the recruitment and consent procedures for the definitive trial, including all proposed information materials the selection of important, relevant, patient-centred primary and secondary outcomes for a definitive trial. Methods Study design This was a mixed-methods study, which employed questionnaires and interviews with parents/legal representatives of children involved in the pilot cRCT and focus groups, as well as an online survey with PICU practitioners (involved in the pilot cRCT and wider UK PICU). Recruitment Parent/legal representatives were recruited via the same process and information materials used in the pilot cRCT. During the recruitment discussion, practitioners invited parents to complete the questionnaire and/or provide contact details if they wished to take part in an interview. Pilot cRCT practitioners were recruited to focus groups via an e-mail invitation, while wider PICU staff were recruited via a Twitter [now X (X Corp., San Francisco, CA, USA); www.twitter.com] advert and presentation (with QR Code link to survey) at the Paediatric Intensive Care Society Study Group biannual meeting. Data collection Informed consent was sought before interviews and focus groups. All methods were online [via Zoom (Zoom Video Communications, San Jose, CA, USA)] or telephone due to the COVID-19 pandemic. Screening and interviews stopped when information power was reached. Parent questionnaires were placed in an envelope and posted to the University of Liverpool team. Sample size It was anticipated that 15–25 parent/legal representatives would be recruited to an interview, that is, until information power and a balance parents of children in each trial arm were reached. Based on previous studies and the pilot cRCT sample size, we aimed to receive approximately 100 parent questionnaires. For practitioners, we aimed to include approximately 8–10 practitioners in each of the focus groups and up to 10 interviews (for those who could not attend a focus group), as well as an online survey using snowball sampling to involve wider PICU staff not involved in the pilot cRCT. Data analysis Qualitative thematic analysis was interpretative and iterative and informed by the constant comparative approach. NVivo 10 software (QSR International, Warrington, UK) was used to assist the coding of data. Survey data were analysed using SPSS version 27 (IBM SPSS Statistics, Armonk, NY, USA) for descriptive statistics. Qualitative and quantitative data were analysed separately and then synthesised through constant comparative analysis. Results A total of 65 parents (44 mothers, 21 fathers) completed the survey across five PICU pilot sites. Of these, 15 (23%) were approached when the child was in the intervention group, 24 (36%) in the control group, and 24 (36%) during ecology week (missing n = 2). Telephone interviews were conducted with 23 parents (7 of which also completed the survey), including 15 mothers (2 ecology week, 7 control and 6 intervention) and 8 fathers (1 ecology week, 4 control and 3 intervention) across five out of the six PICU pilot sites in the UK (3 intervention and 2 control sites). Parents were recruited via sites and 123 parents registered interest. Out of these, 39 were contacted to arrange an interview. Three were no longer interested, six said it was not a good time, and seven did not answer the phone or respond to e-mail. A total of 44 PICU staff completed the survey representing 11 UK PICUs. Of these, 36 (81%) were involved in the PICnIC pilot and were from other PICUs representing six units. Six focus groups with 26 staff were conducted, which was an additional four than originally planned to ensure staff from all PICnIC pilot sites had an opportunity to participate. Overall, the mixed-methods study showed that parents and practitioners found the proposed trial acceptable, but highlighted a number of areas that should be carefully considered when developing the trial protocol and staff site training. Issues with eligible children being missed were due to difficulties in staff knowing whether children would be ventilated for 48 hours, as per the inclusion criteria. Some sites screened more than once up until the 48-hour window, which increased the number of eligible patients identified. Staffing issues due to the pandemic and not remembering to rescreen after the point of admission impacted upon recruitment. Multiple studies recruiting at the same time, as well as difficulties processing samples in overstretched labs, appeared to exacerbate the issues. Staff described how missing data for additional samples was due to concerns about child discomfort, not wishing to broach taking swabs with parents when a child was critically ill, or staff capacity issues. Parents were less concerned about the additional samples, but many stated that consent should be sought prospectively for sample collection. Parents who declined consent for additional samples mentioned their child having gone through a lot and they did not want to add further distress. Having the option to decline certain aspects of trial involvement appeared to make the pilot trial more acceptable for parents. Most parents and staff supported the cRCT design and approach to consent, although any future information materials must make clear that a RWPC approach is being used. Although information leaflets were described as being clear, they were often not read by parents who prioritised discussions with staff. There appeared to be subtle differences in how staff described the nature of the intervention at sites administering SDD, which may have led to parental misconceptions, such as believing that their child would have received the intervention as standard practice outside of the trial. Many parents did not understand that units rather than children had been randomised, as cluster randomisation had not been explained by practitioners. Our findings highlight the need to develop training for recruiters on how to explain the nature of the proposed trial to assist parental understanding, including how whole PICUs are randomised to control or intervention, and the nature of the intervention including information about gut microbiota to address potential parental concerns and to help ensure informed decision-making. Parents’ top prioritised outcomes for the proposed trial were survival and health complications/AEs. Findings suggest that staff were in equipoise and the SDD intervention was acceptable to both parents and staff. Insight from site and wider PICU staff highlights challenges to consider in a definitive proposed trial including delivering the SDD due to the thickness of the paste, sufficient support and engagement of nurse research teams, and sufficient time for trial set-up to help improve trial acceptability and ultimately trial success. Conclusions Insight from parents and PICU staff suggests the proposed trial, SDD intervention and approach to consent was acceptable. Issues such as staff capacity, missed eligible patients and additional sample collection, and parental misunderstandings about the nature of the study were identified. Staff training on recruitment and consent processes is required in any future trial, as well as adaptations on ecology monitoring and dosing regimen of the paste, which should be incorporated into the study design. Patient outcomes for the proposed trial should include complications such as healthcare-acquired infections and antimicrobial use, as well as standard organ failure outcomes such as the need for mechanical ventilation and duration of PICU stay. Recommendations for research A definitive clinical trial for the use of SDD-enhanced infection control using the current PICnIC protocol should not be conducted. A definitive clinical trial for the use of SDD-enhanced infection control using a modified protocol should be conducted. Further work is needed to agree the appropriate measures to monitor ecology in a definitive trial. Trial registration The PICnIC Pilot RCT is registered as Current Controlled Trials ISRCTN40310490. Funding This award was funded by the National Institute for Health and Care Research (NIHR) Health Technology Assessment programme (NIHR award ref: 16/152/01) and is published in Health Technology Assessment; Vol. 28, No. 8. See the NIHR Funding and Awards website for further award information.

IntroductionStroke is a leading cause of death and disability worldwide. Recurrent strokes are seven times more lethal than initial ones, with 54% leading to long-term disability. Substantial recurrent stroke risk disparities exist among ancestral groups. Notably, Africans face double the risk and higher fatality rates compared to Europeans. Although genetic studies, particularly GWAS, hold promise for uncovering biological insights into recurrent stroke, they remain underexplored. Our study addresses this gap through meta-analyses of recurrent stroke GWAS, considering specific ancestral groups and a combined approach.MethodsWe utilized four independent study cohorts for African, European, and Combined ancestry recurrent stroke GWAS with genotyping, imputation, and strict quality control. We harmonized recurrent stroke phenotype and effect allele estimates across cohorts. The logistic regression GWAS model was adjusted for age, sex, and principal components. We assessed how well genetic risk of stroke informs recurrent stroke risk using Receiver Operating Characteristic (ROC) curve analysis with the GIGASTROKE Consortium's polygenic risk scores (PRS).ResultsHarmonization included 4,420 participants (818 African ancestry and 3,602 European ancestry) with a recurrent stroke rate of 16.8% [median age 66.9 (59.1, 73.6) years; 56.2% male]. We failed to find genome-wide significant variants (p < 5e−8). However, we found 18 distinct suggestive (p < 5e−6) genetic loci with high biological relevance consistent across African and European ancestries, including PPARGC1B, CCDC3, OPRL1, and MYH11 genes. These genes affect vascular stenosis through constriction and dilation. We also observed an association with SDK1 gene, which has been previous linked with hypertension in Nigerian and Japanese populations). ROC analysis showed poor performance of the ischemic stroke PRS in discriminating recurrent stroke status (area under the curve = 0.48).DiscussionOur study revealed genetic associations with recurrent stroke not previously associated with incident ischemic stroke. We found suggestive associations in genes previously linked with hypertension. We also determined that knowing the genetic risk of incident stroke does currently not inform recurrent stroke risk. We urgently need more studies to understand better the overlap or lack thereof between incident and recurrent stroke biology.

BackgroundIron and folic acid deficiency is a worldwide public health concern, particularly in low and middle-income countries. In Ethiopia, adherence to iron and folic acid supplements is still very low. Despite the fact that a number of studies on IFA supplementation have been conducted in Ethiopia, they do not indicate a nationwide problem and do not use advanced models to demonstrate clustering effects. The purpose of this study was to assess the level of non-adherence to iron folic acid supplementation and predictors among pregnant women in Ethiopia.ObjectiveTo assess iron folic acid supplementation adherence level and its associated factors among pregnant women in Ethiopia using data from the 2019 Mini-Ethiopian demographic health survey.MethodsThe Mini Ethiopian Demographic and Health Survey 2019 data were obtained from the official database website of the Demographic and Health Survey program (http://dhsprogram.com). The analysis included a sample of 2,356 weighted study participants. A multivariable multilevel mixed-effects logistic regression model was used Variables with p-values less than 5%) was reported as statistically significant variables in the multivariable analysis.ResultsThe proportion of mothers who did not adhere to iron and folic acid supplements was 81.03% (95 %CI, 79.39, and 82.56). Birth interval less than 2 years [AOR: 2.03; 95% CI: 1.12, 3.66], women ever born less than six children [AOR: 1.99; 95% CI: 1.09, 3.64], starting ANC visit during first trimester [AOR: 2.74; 95 %CI: 1.03, 7.30], region [AOR = 0.24; 95% CI: 0.10], and having a high no ANC visit in the community [AOR = 1.77; 95% CI: 1.08, 2.88] were statistically significant factors. There was Intra-Custer Correlation (ICC = 17.72%), indicating that 17.72% variability in non-adherence levels was due to clusters.Conclusion and recommendationIn Ethiopia, nearly four out of every five pregnant women did not receive iron folic acid supplementation for the recommended periods. Birth intervals, number of children, timing of ANC visits, region, and community level no ANC service were significant factors for non-adherence IFAS. As a result, the community, govern metal and non-governmental sectors enacting on health should focus on reducing non-adherence through tailored interventions on factors that influence it.

Sickle cell disease (SCD) is a common genetic disorder with potentially serious sequelae that can be effectively treated with hydroxyurea. Despite its favorable benefit-risk profile, hydroxyurea uptake in patients with SCD is low. A pilot study was conducted at the Southern Alberta Rare Blood and Bleeding Disorders (SARBBDs) Comprehensive Care Program between January 2020 and September 2023 to assess the implementation of a pharmacist-led protocol for supporting the uptake of hydroxyurea among eligible patients with SCD and optimizing its dosing. The protocol standardized the prescription, monitoring, dose titration, and patient counselling by a clinic pharmacist. The number of patients enrolled in the SARBBDs program increased from 98 in January 2020 to 168 in 2023. During this period, the proportion of patients on hydroxyurea increased from 37.8% to 62.5%, the proportion of patients on hydroxyurea who were at a maximum tolerated dose (MTD) increased from 35.1% to 63.8%, and the average hemoglobin F level increased from 13.9% to 19.7%. The mean time to reach MTD was 10 months and required eight pharmacist interventions, six laboratory assessments, and three dose increases. Hydroxyurea continuation rates were high, with most discontinuations resulting from loss to follow-up or transition to a transfusion management strategy. This real-world pilot study demonstrated that implementation of a pharmacist-led prescribing and monitoring protocol nearly doubled hydroxyurea uptake and achievement of MTD in patients with SCD managed in a rare blood disorders clinic.

Aim: Catheter ablation is used to treat symptomatic atrial fibrillation (AF) and is performed using either cryoballoon (CB) or radiofrequency (RF) ablation. There is limited real world data of CB and RF in the US as healthcare codes are agnostic of energy modality. An alternative method is to analyze patients’ electronic health records (EHRs) using Optum’s EHR database. Objective: To determine the feasibility of using patients’ EHRs with natural language processing (NLP) to distinguish CB versus RF ablation procedures. Data Source: Optum de-identified EHR dataset, Optum Cardiac Ablation NLP Table. Methods: This was a retrospective analysis of existing de-identified EHR data. Medical codes were used to create an ablation validation table. Frequency analysis was used to assess ablation procedures and their associated note terms. Two cohorts were created (1) index procedures, (2) multiple procedures. Possible note term combinations included (1) cryoablation (2) radiofrequency (3) ablation, or (4) both. Results: Of the 40,810 validated cardiac ablations, 3777 (9%) index ablation procedures had available and matching NLP note terms. Of these, 22% (n = 844) were classified as ablation, 27% (n = 1016) as cryoablation, 49% (n = 1855) as radiofrequency ablation, and 1.6% (n = 62) as both. In the multiple procedures analysis, 5691 (14%) procedures had matching note terms. 24% (n = 1362) were classified as ablation, 27% as cryoablation, 47% as radiofrequency ablation, and 2%as both. Conclusion: NLP has potential to evaluate the frequency of cardiac ablation by type, however, for this to be a reliable real-world data source, mandatory data entry by providers and standardized electronic health reporting must occur.

Floating Nautical Heritage is part of the Italian Cultural Heritage. Within the mission of the PNRR, it is considered to be a strategic branch for the economic, social, and cultural recovery of our country. In this scenario, Design for Cultural Heritage promotes good practices to reconnect heritages, their users and stakeholders through digital technologies and by enhancing the tangible heritage and their intangible dimension. Thanks to this preface, the paper focuses on Nautical Heritage. It is characterized by a great variety of typologies of goods, both material and intangible, which are currently barely enjoyable. Nevertheless, it has great potential from the economic, social, and cultural points of view. By including the Floating Nautical Heritage in the context of the Design for Cultural Heritage, the authors show innovative strategies focused on the concept of museum of proximity. Two case studies are proposed as pilot experiments that are eventually transferable to others in Italy and abroad.

Falls and osteoporotic fractures are a major public health problem, particularly among older adults. A third of individuals aged 65 years and over fall at least once each year, with up to 20 % of these resulting in serious injury, including fracture. In conjunction with regular exercise, the importance of diet for musculoskeletal health has largely focused upon calcium, vitamin D, and protein, particularly in the context of preventing falls and fractures. Whilst there is evidence for the benefits of these nutrients for musculoskeletal health, other aspects of the diet remain largely underexplored. For example, vegetables are rich sources of macro- and micronutrients that are essential for muscle function and bone health, which are key factors in the prevention of falls and fractures. Recent work has highlighted the importance of nutrients such as vegetable-derived nitrate and vitamin K1 in optimising muscle strength, physical function, and bone quality. In the context of dietary patterns, vegan/plant-based diets have recently gained popularity due to perceived health benefits, animal welfare, or to tackle climate change. The elimination and/or substitution of animal-based products for plant foods (without careful planning and/or expert dietary guidance) could, however, have long-term negative musculoskeletal consequences; a trend uncovered by recent evidence. Within the overarching theme of nutrition for fall and fracture prevention in older populations, the aim of this review is to (i) summarise the current evidence for calcium, vitamin D and protein; (ii) describe the importance of vegetables and selected nutrients, such as nitrate and vitamin K1, for muscle function and bone structural integrity; and (iii) highlight current evidence around different dietary patterns (e.g., plant-based, diet quality, data driven approaches) and their impact on musculoskeletal health.

AbstractA total of 525 catfish samples were collected with various fishing equipment, including hooks, longlines, and different mesh sizes of gillnets (4–12 cm). Out of these specimens, 379 (72.2%) stomachs contained prey items, whereas 146 (27.8%) were empty stomachs. Overall, fish prey, zooplankton, detritus and phytoplankton were the four most important food items, accounting for 48.1%, 21.8%, 17.1% and 5.9% of C. gariepinus diets by volume respectively. Diet composition varied across different size classes of the fish. The smallest fish (37 cm SL) primarily fed on fish prey (14.0–74.1%) followed by zooplankton (11.2–21.3%) by volume. The relative importance of detritus, mud, zooplankton, phytoplankton, and insects decreased with increasing fish size from the Ribb Reservoir. The food and feeding habits of C. gariepinus significantly differed between dry and wet seasons. Fish prey and detritus were mainly consumed in the dry season and contributed to 63.6% and 21.9% of the total volume respectively. Zooplankton and phytoplankton were the most preferred food items during the wet season, contributing 71.8% and 22.2% of the total volume. Generally, C. gariepinus appears to be an omnivore, the species exhibits ontogenetic dietary shifts with larger specimens being more carnivorous, and the species exhibits dietary plasticity across wet and dry seasons, which may be linked to food availability from the Ribb Reservoir.

AbstractThis study aimed to examine the food and feeding habits of Oreochromis niloticus at the Ribb reservoir for sustainable management. A total of 512 specimens were collected using gillnets of different mesh sizes. Of these, 348 (67.9 %) fish had different foods, while 164 (32.1%) fish had empty stomachs. Mud was the main food item that accounted for 89.1% of estimated stomachs and 55.1% of the total volume in the diet. Detritus and phytoplankton were the second most important food items contributing 25.1% and 14.1% of the total volume respectively. Prey items differed depending on the fish size (ANOVA, p

Invasive species are recognized as one of the main causes of erosion of global biodiversity which represent one of the major environmental challenges of the 21st century. Typha is among the fifth most invasive species in West Africa, Nigeria included. Presently in Hadejia Valley Wetlands of Nigeria, typha grass has been perceived as a threat to the surrounding communities. Although some research efforts have shown it can be used as a resource material for renewable energy or animal feed, its use has not yet become a commercial practice. This study investigates compositional characteristic using in vitro digestibility and biogas production from different Typha botanical fractions using anaerobic digestion inoculated with rumen microorganisms. Treatments considered were single plant components as well as combinations. The results show that spike (seed) had the highest soluble crude protein and the leaves had the highest energy content (cellulose and hemicellulose). The leaf and stem at full maturity had a lignin content of 18-20%. Rhizome and stem contained higher ash content while root had greater total volatile solid. The spike yielded the most biogas (457 ml/g) at 60 days retention period. The root component yielded the least gas (259 ml/g) over the same period. The seed pod produced the most methane gas per weight of VS (255 ml/gVS). Blending leaf and stem or root and rhizome increased the volume of biogas generated (399 ml/g and 442 ml/g respectively) while a combination of all components of the plant decreased the volume of gas (388 ml/g – 289 ml/g). The combination of the root and the rhizome produced a higher volume of methane (254 ml/g) than either component by itself (root with 160 ml/g while rhizome 226 ml/g). Different typha components has different compositional characteristic which influence the activity of anaerobic microorganism and affect the volume and quality of biogas produced. Rumen microorganisms digest typha component and spike gives the highest gas volume per grams of typha biomass while rood produce the least volume. Combination of different typha component affect the volume of gas generation defending of which component of plants were mixed.

Abstract This study was aimed at verifying the improvement on the motor impairment and functionality in 19 patients with chronic hemiparesis after stroke treated with a robot-aided rehabilitation protocol using the ReoGo™ system (Motorika Medical Ltd, Israel), and at evaluating the persistence of the effects after 1 month. The study also focused on the actual possibility of administering the robot-aided therapy with the ReoGo™ for the upper limbs and on the patients' degree of acceptance and compliance with the treatment. Subjects underwent an assessment prior to the start of the rehabilitation project (T-1), one at the start (T0), one at the end of the treatment (T1) and one after one month from the end of the treatment (T2). The following tests were administered: (i) Fugl-Meyer (FM) upper limb; Ashworth scale (AS); Functional Independence Measure (FIM™) (T-1 - T2); (ii) strength evaluation; Visual Analogue Scale (VAS) for pain; Frenchay Arm test (FAT); Box and Block test (BBT); Timed Up and Go (TUG) test (T0 - T2). Additionally, the Euro-QoL questionnaire and a VAS for the treatment satisfaction were administered to the subjects. Non-statistical difference of scores at T-1 and T0 on almost the entire battery of tasks suggested a stable patients' performance prior to the start of the rehabilitation. With the exception of the Medical Research Council (MRC) and the AS sub-scales measuring -as appropriate- strength and spasticity of the shoulder, triceps and wrist, all scores showed a significant increase between T0 and T1. The improvement on the pain could not be proved significant (p = 0.10). A significant increase between T0 and T2 was found for all assessment scores, with the exception of the MRC for external shoulder rotators (p = 0.05) and of the AS for shoulder (p = 0.32) and wrist (p = 0.08). Substantial stability was observed between T1 and T2. Patients were capable of completing the treatment and showed good participant satisfaction. This pilot study led to the finding of a clinical improvement and excellent patients compliance. It is possible that the learning process experienced by the patients was robot-dependent, especially in consideration of the general maintenance of the achievements observed on all activities.

Abstract Background Adaptation to hypoxia and consequent pro-inflammatory gene expression of prostate and breast carcinomas have been implicated in the progression toward cancer malignant phenotype. Only partial data are available for the human tumor glioblastoma multiforme (GBM). The aim of our study was to analyze the hypoxic and pro-inflammatory microenvironment in GBMs and to demonstrate that in a stem/progenitor cell line derived from human glioblastoma (GBM-SCs), hypoxia activates a coordinated inflammatory response, evidencing an invasive and migratory phenotype. Methods From each of 10 human solid glioblastomas, clinically and histopathologically characterized, we obtained three surgical samples taken from the center and the periphery of the tumor, and from adjacent host normal tissue. Molecular and morphological analyses were carried out using quantitative real-time PCR and western blot (WB). GBM stem and differentiated cells were incubated under hypoxic conditions and analyzed for pro-inflammatory gene expression and for invasive/migratory behavior. Results A panel of selected representative pro-inflammatory genes (RAGE and P2X7R, COX2, NOS2 and, PTX3) were analyzed, comparing tumor, peritumor and host normal tissues. Tumors containing leukocyte infiltrates (as assessed using CD45 immunohistochemistry) were excluded. Selected genes were overexpressed in the central regions of the tumors (i.e. in the more hypoxic areas), less expressed in peripheral regions, and poorly expressed or absent in adjacent normal host tissues. Western blot analysis confirmed that the corresponding pro-inflammatory proteins were also differently expressed. Hypoxic stem cell lines showed a clear time-dependent activation of the entire panel of pro-inflammatory genes as compared to differentiated tumor cells. Biological assays showed that invasive and migratory behavior was strengthened by hypoxia only in GBM stem cells. Conclusions In human solid glioblastoma we have observed a coordinated overexpression of a panel of pro-inflammatory genes as compared to host normal tissue. We have also evidenced a similar pattern of overexpressed genes in GBM-SCs after hypoxic treatment, showing also a gain of invasive and migratory function that was lost when these stem cells differentiated. We suggest that, as has been previously described for prostatic and mammary carcinoma, in human glioblastoma acquisition of a proinflammatory phenotype may be relevant for malignant progression.

It is important to understand the biological aspects of fish for fishing management. This study was conducted from February through October 2021. A total of 1,629 fishes were collected using different fishing gears. The length-weight relationship is a power curve for all fishes and showed a significant (r2 > 0.8). All fishes revealed a negative allometric growth pattern except Labeobarbus intermedius. Oreochromis niloticus (1.714 ± 0.009) was found in better condition than other fish species (analysis of variance [ANOVA], p < 0.05). The length at maturity was 24.0 cm and 25.4 cm total length (TL), 28.9 cm and 28.2 cm fork length, and 53.2 cm and 57.5 cm TL for females and males of O. niloticus, L. intermedius and Clarias gariepinus, respectively. Fecundity was ranged between 100–947 eggs/g with absolute fecundity (AF) of 468–3,832 eggs, 200–1,000 eggs/g with AF of 2,752–136,420 eggs, and 505–900 eggs/g with AF of 2,000–6,404 eggs for O. niloticus, C. gariepinus, and L. intermedius, respectively. Their respective mean fecundity was 1,490 ± 91, 23,330 ± 5,070, and 3,096 ± 273 eggs, respectively. Mean fecundity revealed a significant variation between size classes and species (ANOVA, p < 0.05). The fecundity length and fecundity-body weight relationships except (O. niloticus) of fishes were curvilinear while the gonad weight (GW)-fecundity relationship was linear for all fish species. The fecundity was moderately associated with increasing length than body weight, and GW for all fishes (r2 > 0.6). In conclusion, a tangible management setup is required to sustain the use of fish in the reservoir.

Non-suicidal self-injury (NSSI) is an increasing phenomenon among both clinical and nonclinical adolescent groups and is associated with several psychopathological symptoms, in addition to being one of the main risk factors for suicidality. Nevertheless, differences between clinical and nonclinical samples of self-harmers in symptom dimensions, alexithymia, suicidality, and NSSI-related variables are still scarcely investigated. The current study aimed to fill this gap by enrolling a sample of Italian girls (age range: 12–19 years) that included 63 self-harmers admitted to mental health outpatient services (clinical group), 44 self-harmers without admission to mental health services (subclinical group), and 231 individuals without an NSSI history (control group). Questionnaires investigating psychopathological symptoms, alexithymia, and NSSI-related variables were administered. The results highlighted that all symptom-related variables and alexithymic traits were more severe in the NSSI groups than in the control group; in particular, self-depreciation, anxiety, psychoticism, and pathological interpersonal relationships were distinguished between the clinical and subclinical groups. Compared to the subclinical group, the clinical group was characterized by higher NSSI frequency, NSSI disclosure, self-punishment as the main reason for engagement in NSSI, and suicidal ideation. These findings were then discussed in terms of clinical practice and primary and secondary prevention in the adolescent population.

Abstract The ADP-ribosyltransferase, PARP1 enzymatically generates and applies the post-translational modification, ADP-Ribose (ADPR). PARP1 roles in genome maintenance are well described, but recent work highlights roles in many fundamental processes including cellular identity and energy homeostasis. Herein, we show in both mouse and human skeletal muscle cells that PARP1-mediated PARylation is a regulator of the myogenic program and the muscle transcriptional response to steroid hormones. Chemical PARP1 modulation impacts the expression of major myocellular proteins, including troponins, key in dictating muscle contractile force. Whilst PARP1 in absence of DNA damage is often assumed to be basally inactive, we show PARylation to be acutely sensitive to extracellular glucose concentrations and the steroid hormone class, glucocorticoids which exert considerable authority over muscle tissue mass. Specifically, we find during myogenesis, a transient and significant rise in PAR. This early-stage differentiation event, if blocked with PARP1 inhibition, reduced the abundance of important muscle proteins in the fully differentiated myotubes. This suggests that PAR targets during early-stage differentiation are central to the proper development of the muscle contractile unit. We also show that reduced PARP1 in myoblasts impacts a variety of metabolic pathways in line with the recorded actions of glucocorticoids. Currently, as both regulators of myogenesis and muscle mass loss, glucocorticoids represent a clinical conundrum. Our work goes on to identify that PARP1 influences transcriptional activation by glucocorticoids of a subset of genes critical to human skeletal muscle pathology. These genes may therefore signify a regulatory battery of targets through which selective glucocorticoid modulation could be achieved. Collectively, our data provide clear links between PARP1-mediated PARylation and skeletal muscle homeostatic mechanisms crucial to tissue mass maintenance and endocrine response.

Abstract Background Addressing the nutritional problems of adolescent girls is important as their nutritional status has a negative effect on the future generation. However, the evidence revealed the variation and unrelated data on the prevalence of dietary diversity and lack of including all adolescent age and community groups in Ethiopia. Hence, this study assessed dietary diversity and associated factors among adolescent girls in Nifas Silk Laphto Sub-city, Addis Ababa Ethiopia, 2021. Methods A community-based cross-sectional study was conducted among 475 adolescent girls at Nifas Silk Laphto sub-city, Addis Ababa Ethiopia from July 1 to 30, 2021. Multistage cluster sampling was employed to select adolescent girls. Pretested questionnaires were used to collect the data. The data were checked for completeness and entered by Epidata version 3.1 and cleaned and analyzed by SPSS version 21.0. A multivariable binary logistic regression model was fitted to identify factors associated with dietary diversity scores. The degree of association was assessed using an odds ratio with a 95% confidence interval and variables with p-value ≤ 0.05 were considered significant. Result The mean and the standard deviation of dietary diversity scores were 4.70 and 1.21 respectively. The proportion of low dietary diversity scores among adolescent girls was 77.2%. Adolescent girls’ age, meal frequency, wealth index of household, and food insecurity were significant determinants of dietary diversity score. Conclusion The magnitude of low dietary diversity scores was significantly higher in the study area. Adolescent girls’, meal frequency, wealth index, and food security status were predictors of dietary diversity score. School-based nutrition education and counseling and designing strategies for improving household food security programs are crucial.

Laccases from white-rot fungi catalyze lignin depolymerization, a critical first step to upgrading lignin to valuable biodiesel fuels and chemicals. In this study, a wildtype laccase from the basidiomycete Fomitiporia mediterranea (Fom_lac) and a variant engineered to have a carbohydrate-binding module (Fom_CBM) were studied for their ability to catalyze cleavage of β-O-4′ ether and C–C bonds in phenolic and non-phenolic lignin dimers using a nanostructure-initiator mass spectrometry-based assay. Fom_lac and Fom_CBM catalyze β-O-4′ ether and C–C bond breaking, with higher activity under acidic conditions (pH < 6). The potential of Fom_lac and Fom_CBM to enhance saccharification yields from untreated and ionic liquid pretreated pine was also investigated. Adding Fom_CBM to mixtures of cellulases and hemicellulases improved sugar yields by 140% on untreated pine and 32% on cholinium lysinate pretreated pine when compared to the inclusion of Fom_lac to the same mixtures. Adding either Fom_lac or Fom_CBM to mixtures of cellulases and hemicellulases effectively accelerates enzymatic hydrolysis, demonstrating its potential applications for lignocellulose valorization. We postulate that additional increases in sugar yields for the Fom_CBM enzyme mixtures were due to Fom_CBM being brought more proximal to lignin through binding to either cellulose or lignin itself.

Sufficient high-quality studies in sport science using women as participants are lacking, meaning that our knowledge and understanding of female athletes in relation to their ovarian hormone profiles is limited. Consortia can be used to pool talent, expertise and data, thus accelerating our learning on a given topic and reducing research waste through collaboration. To this end, we have assembled an international multisite team, described here, to investigate the effects of the menstrual cycle and contraceptive pill phase on aspects of exercise physiology and sports performance in female athletes. We intend to produce an adequately powered, high-quality dataset, which can be used to inform the practices of female athletes. Our approach will also employ research transparency—through the inclusion of a process evaluation—and reproducibility—through a standardised study protocol.