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We report measurements of the charged daughter fraction of 218Po as a result of the 222Rn alpha decay, and the mobility of 218Po+ ions, using radon-polonium coincidences from the 238U chain identified in 532 live-days of DarkSide-50 WIMP-search data. The fraction of 218Po that is charged is found to be 0.37 ± 0.03 and the mobility of 218Po+ is (8.6 ± 0.1) × 10−4 cmVs2.

The differential urbanisation model is a means to assess settlement growth rates. While the model has been tested primarily at a national level, including in South Africa, this study seeks to apply the analysis to the sub-national scale in the Western Cape province and Cape Winelands district municipality. The study found that the model is applicable to both the province and the district municipality. Settlements of differing size and economic importance grew at varying rates relative to each other in a predictable sequence, which realised the urban hierarchy, over a 20-year period. This finding was unexpected, given that the urban differential model assumes economic growth as well as labour and socio-economic homogeneity – factors that have not been evenly sub-nationally. The applicability of the model to these locations may assist in the public division of resources, particularly in small towns, where meaningful urbanisation occurs, yet capital allocations are limited. The applicability of the study is in keeping with national, provincial, and municipal trends in planning that emphasise the interrelationship between settlements of different size and function over time, and the importance of spatial planning in guiding public infrastructure expenditure.

The use of "belly scoring" can offer a novel, non-invasive objective management tool to gauge food intake between individuals, groups, and populations, and thus, population fitness. As food availability is increasingly affected by predation, ecological competition, climate change, habitat modification, and other human activities, an accurate belly scoring tool can facilitate comparisons among wildlife populations, serving as an early warning indicator of threats to wildlife population health and potential population collapse. In social species, belly scores can also be a tool to understand social behavior and ranking. We developed and applied the first rigorous quantitative photogrammetric methodology to measure belly scores of wild painted dogs (Lycaon pictus). Our methodology involves: (1) Rigorous selection of photographs of the dorso/lateral profile of individuals at a right angle to the camera, (2) photogrammetrically measuring belly chord length and "belly drop" in pixels, (3) adjusting belly chord length as a departure from a standardized leg angle, and (4) converting pixel measurements to ratios to eliminate the need to introduce distance from the camera. To highlight a practical application, this belly score method was applied to 631 suitable photographs of 15 painted dog packs that included 186 individuals, all collected between 2004-2015 from allopatric painted dog populations in and around Hwange (n = 462) and Mana Pools National Parks (n = 169) in Zimbabwe. Variation in mean belly scores exhibited a cyclical pattern throughout the year, corresponding to biologically significant patterns to include denning demand and prey availability. Our results show significant differences between belly scores of the two different populations we assessed, thus highlighting food stress in the Hwange population. In the face of growing direct and indirect anthropogenic disturbances, this standardised methodology can provide a rapid, species-specific non-invasive management tool that can be applied across studies to rapidly detect emergent threats.

Abstract Background Gene expression profiles of intestinal mucosa of chickens and pigs fed over long-term periods (days/weeks) with a diet rich in rye and a diet supplemented with zinc, respectively, or of chickens after a one-day amoxicillin treatment of chickens, were recorded recently. Such dietary interventions are frequently used to modulate animal performance or therapeutically for monogastric livestock. In this study, changes in gene expression induced by these three interventions in cultured “Intestinal Porcine Epithelial Cells” (IPEC-J2) recorded after a short-term period of 2 and 6 hours, were compared to the in vivo gene expression profiles in order to evaluate the capability of this in vitro bioassay in predicting in vivo responses. Methods Lists of response genes were analysed with bioinformatics programs to identify common biological pathways induced in vivo as well as in vitro. Furthermore, overlapping genes and pathways were evaluated for possible involvement in the biological processes induced in vivo by datamining and consulting literature. Results For all three interventions, only a limited number of identical genes and a few common biological processes/pathways were found to be affected by the respective interventions. However, several enterocyte-specific regulatory and secreted effector proteins that responded in vitro could be related to processes regulated in vivo, i.e. processes related to mineral absorption, (epithelial) cell adherence and tight junction formation for zinc, microtubule and cytoskeleton integrity for amoxicillin, and cell-cycle progression and mucus production for rye. Conclusions Short-term gene expression responses to dietary interventions as measured in the in vitro bioassay have a low predictability for long-term responses as measured in the intestinal mucosa in vivo. The short-term responses of a set regulatory and effector genes, as measured in this bioassay, however, provided additional insight into how specific processes in piglets and broilers may be modulated by “early” signalling molecules produced by enterocytes. The relevance of this set of regulatory/effector genes and cognate biological processes for zinc deficiency and supplementation, gluten allergy (rye), and amoxicillin administration in humans is discussed.

Summary: Background: A comprehensive evaluation of the burden of injury is an important foundation for selecting and formulating strategies of injury prevention. We present results from the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2017 of non-fatal and fatal outcomes of injury at the national and subnational level, and the changes in burden for key causes of injury over time in China. Methods: Using the methods and results from GBD 2017, we describe the burden of total injury and the key causes of injury based on the rates of incidence, cause-specific mortality, and disability-adjusted life years (DALYs) in China estimated using DisMod-MR 2.1. We additionally evaluated these results at the provincial level for the 34 subnational locations of China in 2017, measured the change of injury burden from 1990 to 2017, and compared age-standardised DALYs due to injuries at the provincial level against the expected rates based on the Socio-demographic Index (SDI), a composite measure of development of income per capita, years of education, and total fertility rate. Findings: In 2017, in China, there were 77·1 million (95% uncertainty interval [UI] 72·5–81·6) new cases of injury severe enough to warrant health care and 733 517 deaths (681 254–767 006) due to injuries. Injuries accounted for 7·0% (95% UI 6·6–7·2) of total deaths and 10·0% (9·5–10·5) of all-cause DALYs in China. In 2017, there was a three-times variation in age-standardised injury DALY rates between provinces of China, with the lowest value in Macao and the highest in Yunnan. Between 1990 and 2017, the age-standardised incidence rate of all injuries increased by 50·6% (95% UI 46·6–54·6) in China, whereas the age-standardised mortality and DALY rates decreased by 44·3% (41·1–48·9) and 48·1% (44·6–51·8), respectively. Between 1990 and 2017, all provinces of China experienced a substantial decline in DALY rates from all injuries ranging from 16·3% (3·1–28·6) in Shanghai and 60·4% (53·7–66·1) in Jiangxi. Age-standardised DALY rates for drowning; injuries from fire, heat and hot substances; adverse effects of medical treatments; animal contact; environmental heat and cold exposure; self-harm; and executions and police conflict each declined by more than 60% between 1990 and 2017. Interpretation: Between 1990 and 2017, China experienced a decrease in the age-standardised DALY and mortality rates due to injury, despite an increase in the age-standardised incidence rate. These trends occurred in all provinces. The divergent trends in terms of incidence and mortality indicate that with rapid sociodemographic improvements, the case fatality of injuries has declined, which could be attributed to an improving health-care system but also to a decreasing severity of injuries over this time period. Funding: Bill & Melinda Gates Foundation.

Summary: Background: India has 18% of the global population and an increasing burden of chronic respiratory diseases. However, a systematic understanding of the distribution of chronic respiratory diseases and their trends over time is not readily available for all of the states of India. Our aim was to report the trends in the burden of chronic respiratory diseases and the heterogeneity in their distribution in all states of India between 1990 and 2016. Methods: Using all accessible data from multiple sources, we estimated the prevalence of major chronic respiratory diseases and the deaths and disability-adjusted life-years (DALYs) caused by them for every state of India from 1990 to 2016 as part of the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2016. We assessed heterogeneity in the burden of chronic obstructive pulmonary disease (COPD) and asthma across the states of India. The states were categorised into four groups based on their epidemiological transition level (ETL). ETL was defined as the ratio of DALYs from communicable diseases to those from non-communicable diseases and injuries combined, with a low ratio denoting high ETL and vice versa. We also assessed the contribution of risk factors to DALYs due to COPD. We compared the burden of chronic respiratory diseases in India against the global average in GBD 2016. We calculated 95% uncertainty intervals (UIs) for the point estimates. Findings: The contribution of chronic respiratory diseases to the total DALYs in India increased from 4·5% (95% UI 4·0–4·9) in 1990 to 6·4% (5·8–7·0) in 2016. Of the total global DALYs due to chronic respiratory diseases in 2016, 32·0% occurred in India. COPD and asthma were responsible for 75·6% and 20·0% of the chronic respiratory disease DALYs, respectively, in India in 2016. The number of cases of COPD in India increased from 28·1 million (27·0–29·2) in 1990 to 55·3 million (53·1–57·6) in 2016, an increase in prevalence from 3·3% (3·1–3·4) to 4·2% (4·0–4·4). The age-standardised COPD prevalence and DALY rates in 2016 were highest in the less developed low ETL state group. There were 37·9 million (35·7–40·2) cases of asthma in India in 2016, with similar prevalence in the four ETL state groups, but the highest DALY rate was in the low ETL state group. The highest DALY rates for both COPD and asthma in 2016 were in the low ETL states of Rajasthan and Uttar Pradesh. The DALYs per case of COPD and asthma were 1·7 and 2·4 times higher in India than the global average in 2016, respectively; most states had higher rates compared with other locations worldwide at similar levels of Socio-demographic Index. Of the DALYs due to COPD in India in 2016, 53·7% (43·1–65·0) were attributable to air pollution, 25·4% (19·5–31·7) to tobacco use, and 16·5% (14·1–19·2) to occupational risks, making these the leading risk factors for COPD. Interpretation: India has a disproportionately high burden of chronic respiratory diseases. The increasing contribution of these diseases to the overall disease burden across India and the high rate of health loss from them, especially in the less developed low ETL states, highlights the need for focused policy interventions to address this significant cause of disease burden in India. Funding: Bill & Melinda Gates Foundation; and Indian Council of Medical Research, Department of Health Research, Ministry of Health and Family Welfare, Government of India.

Summary: Background: The Sustainable Development Goals (SDGs) mandate systematic monitoring of the health and wellbeing of all children to achieve optimal early childhood development. However, global epidemiological data on children with developmental disabilities are scarce. The Global Burden of Diseases, Injuries, and Risk Factors Study 2016 provides a comprehensive assessment of prevalence and years lived with disability (YLDs) for development disabilities among children younger than 5 years in 195 countries and territories from 1990 to 2016. Methods: We estimated prevalence and YLDs for epilepsy, intellectual disability, hearing loss, vision loss, autism spectrum disorder, and attention deficit hyperactivity disorder. YLDs were estimated as the product of the prevalence estimate and the disability weight for each mutually exclusive disorder, corrected for comorbidity. We used DisMod-MR 2.1, a Bayesian meta-regression tool, on a pool of primary data derived from systematic reviews of the literature, health surveys, hospital and claims databases, cohort studies, and disease-specific registries. Findings: Globally, 52·9 million (95% uncertainty interval [UI] 48·7–57·3; or 8·4% [7·7–9·1]) children younger than 5 years (54% males) had developmental disabilities in 2016 compared with 53·0 million (49·0–57·1; or 8·9% [8·2–9·5]) in 1990. About 95% of these children lived in low-income and middle-income countries. YLDs among these children increased from 3·8 million (95% UI 2·8–4·9) in 1990 to 3·9 million (2·9–5·2) in 2016. These disabilities accounted for 13·3% of the 29·3 million YLDs for all health conditions among children younger than 5 years in 2016. Vision loss was the most prevalent disability, followed by hearing loss, intellectual disability, and autism spectrum disorder. However, intellectual disability was the largest contributor to YLDs in both 1990 and 2016. Although the prevalence of developmental disabilities among children younger than 5 years decreased in all countries (except for North America) between 1990 and 2016, the number of children with developmental disabilities increased significantly in sub-Saharan Africa (71·3%) and in North Africa and the Middle East (7·6%). South Asia had the highest prevalence of children with developmental disabilities in 2016 and North America had the lowest. Interpretation: The global burden of developmental disabilities has not significantly improved since 1990, suggesting inadequate global attention on the developmental potential of children who survived childhood as a result of child survival programmes, particularly in sub-Saharan Africa and south Asia. The SDGs provide a framework for policy and action to address the needs of children with or at risk of developmental disabilities, particularly in resource-poor countries. Funding: The Bill & Melinda Gates Foundation.

Human intestinal tissue samples are barely accessible to study potential health benefits of nutritional compounds. Numbers of animals used in animal trials, however, need to be minimalized. Therefore, we explored the applicability of in vitro (human Caco-2 cells) and ex vivo intestine models (rat precision cut intestine slices and the pig in-situ small intestinal segment perfusion (SISP) technique) to study the effect of food compounds. In vitro digested yellow (YOd) and white onion extracts (WOd) were used as model food compounds and transcriptomics was applied to obtain more insight into which extent mode of actions depend on the model. The three intestine models shared 9,140 genes which were used to compare the responses to digested onions between the models. Unsupervised clustering analysis showed that genes up- or down-regulated by WOd in human Caco-2 cells and rat intestine slices were similarly regulated by YOd, indicating comparable modes of action for the two onion species. Highly variable responses to onion were found in the pig SISP model. By focussing only on genes with significant differential expression, in combination with a fold change > 1.5, 15 genes showed similar onion-induced expression in human Caco-2 cells and rat intestine slices and 2 overlapping genes were found between the human Caco-2 and pig SISP model. Pathway analyses revealed that mainly processes related to oxidative stress, and especially the Keap1-Nrf2 pathway, were affected by onions in all three models. Our data fit with previous in vivo studies showing that the beneficial effects of onions are mostly linked to their antioxidant properties. Taken together, our data indicate that each of the in vitro and ex vivo intestine models used in this study, taking into account their limitations, can be used to determine modes of action of nutritional compounds and can thereby reduce the number of animals used in conventional nutritional intervention studies.

Aims: Salmonella infections are significant causes of foodborne outbreaks in the European Union. This study investigates a sudden increase in gastroenteritis patients in the hospital district of Central Finland in June 2021. The primary aim was to study the outbreak's magnitude and source of the outbreak., Methods and Results: Epidemiological, microbiological, environmental and traceback investigations were conducted. Over 700 persons fell ill during the outbreak caused by Salmonella Typhimurium associated with a daycare lunch. Similar S. Typhimurium was found in the patients and a vegetable mix containing iceberg lettuce, cucumber and peas served during lunch. The traceback investigation revealed that the batch information of vegetables from the wholesaler was not complete. The wholesaler had received quality complaints about the iceberg lettuce from the central kitchen. The manufacturer did not test the suspected batch for Salmonella since the production plant had given a certificate declaring it Salmonella negative., Conclusions: The most suspect ingredient was one batch of iceberg lettuce due to quality complaints. The lettuce had not been served in two daycare centres without cases. We recommend that in order to enable thorough microbiological investigation, institutional kitchens store the food samples separately as part of the internal quality control and that food items should always be tested when Salmonella contamination in an outbreak is suspected., (© 2024 The Author(s). Zoonoses and Public Health published by Wiley‐VCH GmbH.)

Background: Desk-work-related musculoskeletal pain is more prevalent among female workers than male workers. This may be contributed to by sex and/or gender differences in postural variability however, the mechanisms underpinning these differences are poorly understood. This review investigates whether desk-based postural variability studies investigate sex-gender differences and, how they explain the mechanisms behind these differences., Methods: A scoping review was conducted with four databases (PubMed, Embase, Scopus and ProQuest) searched in June and July 2023. Studies investigating postural variability among desk-based workers were included and a narrative approach used to synthesise results., Results: 15 studies were included. Only four reported on sex-gender differences. None collected psychological or social information to explore reasons for sex-gender differences., Conclusion: The mechanisms behind postural variability differences between sexes and genders are complex and multifactorial. Studies largely do not consider sex and gender and do not collect the information necessary to explain their results.

Objective: Female sexual problems are common but are not routinely assessed in obstetrician-gynecologist appointments. Therefore, we evaluated obstetrician-gynecologists' attitudes and practice patterns regarding their patients' sexual problems., Study Design: A web-based questionnaire was used to collect information from each respondent on gender, age, education, occupational status, and the total number of patients treated per day and sexual issues dealt with per day., Main Outcome Measures: This study covered three fields of interest: 1) attitudes toward sexual problems, 2) practice patterns in sexual history-taking, and 3) practice patterns in the treatment of sexual problems., Results: Of the 328 respondents, 299 provided eligible responses (specialists, 83 %, n = 249; residents, 17 %, n = 50). Almost all obstetrician-gynecologists (95 %) considered treating sexual problems as an important health care practice, but only 45 % and 53 % asked about sexual problems and sexual life satisfaction during general medical history-taking, respectively. Most obstetrician-gynecologists (86 %) used open conversation to assess sexual history. Half (52 %) of them reported that diagnosing female sexual problems is difficult, with the female obstetrician-gynecologists (54 %) more likely to report difficulty than the male obstetrician-gynecologists (29 %). Of the obstetrician-gynecologists, 15 % prescribed medications, whereas 58 % prescribed other treatments. A third (34 %) received distinct instructions from their organization for referring patients to continued care., Conclusions: Although almost all obstetrician-gynecologists reported that treating sexual problems is an important health care issue, fewer than half routinely inquired about sexual problems. The practice patterns regarding sexual problems were disorganized. Our results show a need for additional clinical practice guidelines and education in sexual medicine., Competing Interests: Declaration of competing interest The authors declare that they have no competing interest., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Study Design: Cross-sectional survey of the Finnish population with spinal cord injury (SCI)., Objectives: To explore the frequencies of perceived environmental barriers (EB) that made participation harder for the Finnish population with SCI and to compare the occurrence of perceived EBs by gender, age, time since injury, and injury severity., Setting: Participants were recruited from the registers of the three SCI outpatient clinics responsible for the lifelong care of people with SCI in Finland., Methods: The self-administered Nottwil Environmental Factors Inventory Short Form (NEFI-SF) collected in the Finnish Spinal Cord Injury Study (FinSCI) (n = 1772) was used. Nonparametric tests and multinomial logistic regression models were utilized., Results: 880 individuals responded to the NEFI-SF items (response rate 50%). Climate was perceived as a barrier by 72% and a serious one by 44% of the respondents. The rates regarding public access were 59% and 24%, private home access 46% and 18%, and long-distance transport 45% and 20%. Four out of ten respondents reported that finances, lack of assistive devices for short-distance transport, and political decisions restricted their participation. The NEFI-SF total scores were higher (meaning more perceived restrictions by EBs) for those more severely injured., Conclusions: Climate, access to public and private places, challenges with transport, finances, and political decisions were the EBs most frequently perceived to restrict participation by the Finnish population with SCI. Most EBs that were prominent causes of restrictions are modifiable. Greater accessibility to the built environment, equal services to all, and positive special treatment could reduce their effects., (© 2024. The Author(s).)

Introduction: Many elements of life can affect sexual health; thus, healthcare professionals require good knowledge of sexual medicine to encounter patients with these issues. We aimed to study final-year medical and midwifery students' self-reported knowledge of factors associated with sexuality and their knowledge of how to evaluate and treat/counsel patients with sexual problems. In addition, educational interests regarding sexual medicine were assessed., Methods: In a cross-sectional study, a web-based questionnaire was distributed to final-year medical (n=233) and midwifery (n=131) students graduating between December 2018 and May 2019 in Finland., Results: Both student groups self-reported insufficient knowledge of how to consider sexuality in mentally ill patients, how to encounter victims of domestic violence/sexual abuse, and how multiculturalism affects sexuality. In addition, compared to the midwifery students, the medical students were more likely to self-report insufficient knowledge of the basics of sexual pleasure and treating the lack of it (p<0.001), including how to treat sexual problems due to relationship problems (p<0.001) or chronic diseases (p=0.015). Although several educational areas of interest arose, both student groups had two mutual most desirable educational interests: 1) reasons for dyspareunia and its treatment, n=117/233 (50.2%) for medical students, and n=60/131 (45.8%) for midwifery students; and 2) lack of sexual desire and its treatment, n=100/233 (42.9%) for medical students, and n=55/131 (42.0%) for midwifery students., Conclusions: In both student groups, the self-reported knowledge of sexual medicine was insufficient. Thus, more education on sexual medicine should be included in the curricula of medical and midwifery education., Competing Interests: The authors have each completed and submitted an ICMJE form for Disclosure of Potential Conflicts of Interest. The authors declare that they have no competing interests, financial or otherwise, related to the current work. S-M Manninen reports receiving article processing charges for the present manuscript covered by Research Services, Wellbeing services county of Southwest Finland. She also reports that the results of the present manuscript were presented in the EMA Education Conference, 33rd ICM Triennial Congress, and that the participation fees, travel and accommodation expenses were covered by Metropolia University of Applied Sciences. Furthermore, she reports receiving research grants from the Finnish Medical Society Duodecim, and the Federation of Finnish Midwives, and Turku University Hospital (Special Government Funding)., (© 2024 Manninen S.M. et al.)

Background: Nontechnical skills in cardiac surgery are vital in ensuring patient safety in the operating room (OR). To train these skills in a simulation-based scenario, a collection of commonly accepted crisis scenarios is needed to serve as a framework for a simulation-based training program., Objective: The objective of this study was to identify and reach consensus on a collection of relevant crisis scenarios in cardiac surgery suitable for simulation-based team training focusing on nontechnical skills., Methods: Using the Delphi method, a national assessment was performed among cardiac surgeons, cardiac anesthesiologists, clinical perfusionists, and cardiac OR nurses in the Netherlands. In the first Delphi round, potential crisis scenarios for simulation-based team training in cardiac surgery were identified. In the second round, the identified scenarios were rated using a 5-point Likert scale. Finally, based on consensus (two-thirds majority), scenarios were prioritized and explored for feasibility., Results: One hundred fourteen experts participated in the study (26 cardiac anesthesiologists, 24 cardiac surgeons, 25 clinical perfusionists, and 39 OR nurses), representing all 16 cardiac surgical centers in the Netherlands. In the first round, 237 scenarios were identified. After eliminating duplicates and grouping similar scenarios, 44 scenarios were scored in round 2, which finally resulted in 13 relevant crisis scenarios with an expert consensus higher than 67%., Conclusions: Thirteen crisis scenarios relevant to simulation-based team training were identified by an expert panel consisting of all members of the cardiac surgical team. Further research is needed to evaluate the educational value of the respective scenarios., Competing Interests: The authors declare no conflict of interest., (Copyright © 2023 Society for Simulation in Healthcare.)

We present a search for dark matter particles with sub-GeV/c^{2} masses whose interactions have final state electrons using the DarkSide-50 experiment's (12 306±184)  kg d low-radioactivity liquid argon exposure. By analyzing the ionization signals, we exclude new parameter space for the dark matter-electron cross section σ[over ¯]&#95;{e}, the axioelectric coupling constant g&#95;{Ae}, and the dark photon kinetic mixing parameter κ. We also set the first dark matter direct-detection constraints on the mixing angle |U&#95;{e4}|^{2} for keV/c^{2} sterile neutrinos.

Dark matter elastic scattering off nuclei can result in the excitation and ionization of the recoiling atom through the so-called Migdal effect. The energy deposition from the ionization electron adds to the energy deposited by the recoiling nuclear system and allows for the detection of interactions of sub-GeV/c^{2} mass dark matter. We present new constraints for sub-GeV/c^{2} dark matter using the dual-phase liquid argon time projection chamber of the DarkSide-50 experiment with an exposure of (12 306±184)  kg d. The analysis is based on the ionization signal alone and significantly enhances the sensitivity of DarkSide-50, enabling sensitivity to dark matter with masses down to 40  MeV/c^{2}. Furthermore, it sets the most stringent upper limit on the spin independent dark matter nucleon cross section for masses below 3.6  GeV/c^{2}.

Introduction: Sexual health is an important aspect of quality of life, yet both healthcare professionals and patients might hesitate to bring up the topic during appointments. Our study investigated obstetrician-gynecologists' (OB/GYNs') self-reported competences in discussing and treating sexual problems, as well as the barriers to bringing up the subject. An additional aim was to evaluate the need for continuing education in sexual medicine., Material and Methods: A web-based questionnaire was sent to the members of The Finnish Society of Obstetrics and Gynecology (n = 1212). The survey was completed by 328 respondents (275 specialists and 53 OB/GYN residents). Their background information (gender, age, education, occupational status, daily number of patients, and daily number of patients with sexual health issues) was assessed. The questionnaire included four fields: (A) self-reported competence in discussing and treating patients with sexual problems (three questions), (B) the barriers to bringing up sexual problems with patients (nine questions), (C) the source of education in sexual medicine (two questions), and (D) the need for education in sexual medicine (two questions)., Results: Most of the OB/GYNs self-reported their competence to be good in discussing sexual problems, but poor in treating patients' sexual problems. The male OB/GYNs reported better competence than did the females. Several barriers were identified-most frequently, "shortness of the appointment time" (76%), "lack of knowledge about sexual medicine" (75%), and "lack of experience with sexual medicine" (74%). Older OB/GYNs and male OB/GYNs reported fewer barriers. The majority of the respondents considered their previous education in sexual medicine to be insufficient, especially in medical school (95%), but also in residency (83%), and they reported a need for additional education., Conclusions: Our study indicated several barriers that hindered OB/GYNs from assessing sexual problems during appointments. Although OB/GYNs reported a good competence in discussing sexual problems, they reported a poor competence in treating them. Their previous education in sexual medicine was rated as insufficient, and continuing education was desired. The information provided by our study can be used for improving and organizing education in sexual medicine, which is crucial for diminishing the barriers to discussing and treating sexual problems., (© 2022 The Authors. Acta Obstetricia et Gynecologica Scandinavica published by John Wiley & Sons Ltd on behalf of Nordic Federation of Societies of Obstetrics and Gynecology (NFOG).)

Background: Anxiety is a prominent disabling non-motor neuropsychiatric complication of Parkinson's disease (PD). Pharmacological treatments for PD and anxiety have drug interactions and negative side effects. Therefore, non-pharmacological interventions such as exercise has been proposed to reduce anxiety in people with PD (PwP)., Objective: This systematic review aimed to explore the relationship between physical exercise and anxiety in PwP., Method: Four databases (PubMed, Embase, Scopus, Ebscohost) were searched without date restrictions. English randomized control trials (RCT) including adults with PD, exposed to physical exercise interventions with anxiety as an outcome variable, were included. Quality was assessed by means of an adapted 9-point PEDro scale., Results: Five of the identified 5547 studies met the inclusion criteria. Sample size ranged between 11-152 participants, totaling 328 participants with majority being male. PD stage ranged from early to moderate, with disease duration ranged between 2.9 and 8.0 years. All studies measured anxiety at baseline and post-intervention. On average studies scored 7/9 (76%) on the PEDro scale., Conclusion: There is insufficient evidence to support or refute the effect of exercise on anxiety in PwP due to noted limitations of included studies. There is an urgent need for high-quality RCTs on physical exercise and anxiety in PwP.

Objectives: Physicians and midwives meet patients with sexual health issues regularly; however, they may have limited sexual medicine education. The study's aim was to evaluate the self-reported competence of medical and midwifery students to bring up sexual health issues with their patients and to assess the barriers that hinder these discussions. The need for additional education was also evaluated., Study Design: A web-based questionnaire was sent to the last-year medical and midwifery students graduating between December 2018 and May 2019 in Finland. In total, 233 medical students and 131 midwifery students participated in the study. Three fields were evaluated: the self-reported competence in discussing sexual health issues and treating patients with these issues, the barriers to bringing up sexual problems, and the need for education in sexual medicine., Results: The students self-reported better competence in discussing sexual health issues than in treating patients' sexual problems. For the medical students, the most important barriers hindering bringing up sexual health issues were lack of i) time (89.2 %), ii) experience with sexual medicine (88.1 %), and iii) knowledge (82.1 %). For the midwifery students, the most important barriers were i) lack of experience with sexual medicine (73.3 %), ii) fear of failing to respond to patients' sexual health issues (64.9 %), and iii) lack of knowledge (62.5 %). A higher percentage of the midwifery students (96.2 %) reported an interest in sexual medicine education compared to the medical students (55.4 %) (OR 13.89, 95 % CI 5.32-35.71, P <.001). Majority (76.5 %) of the medical students and almost half (45.0 %) of the midwifery students reported receiving too little sexual medicine education (OR 7.30, 95 % CI 4.00-13.33, P <.001)., Conclusions: Both student groups reported several barriers hindering bringing up sexual health issues with their patients and expressed a need for more education, particularly the medical students., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 The Authors. Published by Elsevier B.V. All rights reserved.)

Around the world, many couples have turned to in vitro fertilization as a viable solution to fertility issues. Low-density lipoprotein (LDL) is a protein best known for transporting fat molecules throughout the body, but it has also been shown to protect sperm cells during cryopreservation due to its micellar structure. In the present study, we aimed to evaluate different protocols for the preparation of nanoparticles from egg yolk plasma (EYP) containing LDL to improve the viability of cryopreserved canine semen. EYP was subjected to three distinct treatments: ultrasonification in an ultrasound bath at 40 kHz for 30 min (LDL-B); ultrasonification via an ultrasound probe at 50% amplitude for 30 min (LDL-P); and high-pressure homogenization at 10,000 PSI for six cycles (LDL-H). Sperm quality was assessed after thawing using computer-assisted sperm analysis and flow cytometry. The results revealed that compared to the EYP control, the LDL-P formulation presented significantly higher efficiency (p < 0.05) in maintaining total and progressive sperm motility, sperm membrane integrity and fluidity, and levels of intracellular reactive oxygen species. The LDL-P nanoparticles had an average size of approximately 250 nm, a PDI value of 0.3, and -1.15 mV of zeta potential, which are very important because it is an indicator of the stability of a colloidal dispersion. Therefore, we conclude that ultrasonication of EYP using a probe is an efficient method for the preparation of LDL nanoparticles that would enhance the cryoprotection of semen during freezing., Competing Interests: Conflicts of interest The authors declare that they do not have any commercial or associative interest that represents a conflict of interest in connection with the work submitted., (Copyright © 2022. Published by Elsevier Inc.)

Objectives: Many chronic diseases and their medications may induce sexual problems. This study aimed to evaluate whether general practitioners (GPs) raise sexual health issues during appointments with patients who have chronic diseases., Study Design: A web-based questionnaire was distributed to a random sample of 1,000 GPs in Finland., Main Outcome Measures: The study aim was to determine GPs' self-reported inquiry into sexual problems with patients who have chronic diseases and GPs' awareness of medications inducing sexual problems., Results: Only 16.2% of the GPs inquired about sexual health issues, typically during appointments dealing with reproductive organs. A majority (66.9%) considered sexual problems to be side-effects of medications, but only 17.9% followed up about them. Compared to male GPs, female GPs were more likely to inquire about gynecologic patients' sexual issues (OR 1.77, 95% CI 1.05-2.99), but less likely to ask about them with urologic (OR 0.56, 95% CI 0.35-0.91) and neurologic patients (OR 0.35, 95% CI 0.17-0.72). The GPs aged 40-49 and 50-65 were more likely than those aged 27-39 to inquire about sexual health issues among patients with cardiovascular (OR 2.87, 95% CI 1.11-7.44, OR 2.89, 95% CI 1.16-7.19) and neurologic (OR 4.63, 95% CI 1.45-14.82, OR 5.68, 95% CI 1.87-17.23) diseases., Conclusions: GPs seldom inquire about sexual problems with patients who have chronic diseases or after prescribing medications for these conditions, which may lead to underdiagnosis and undertreatment of sexual problems., Competing Interests: The authors have no competing interests pertaining to this paper., (Copyright © 2022. Published by Elsevier B.V.)

Monocytes expressing the inflammation suppressing active CD11b, a beta2 integrin, may regulate neuroinflammation and modify clinical outcomes in amyotrophic lateral sclerosis (ALS). In this single site, retrospective study, peripheral blood mononuclear cells from 38 individuals living with ALS and 20 non-neurological controls (NNC) were investigated using flow cytometry to study active CD11b integrin classical (CM), intermediate (IM) and non-classical (NCM) monocytes during ALS progression. Seventeen ALS participants were sampled at the baseline (V1) and at two additional time points (V2 and V3) for longitudinal analysis. Active CD11b+ CM frequencies increased steeply between the baseline and V3 (ANOVA repeated measurement, p < 0.001), and the V2/V1 ratio negatively correlated with the disease progression rate, similar to higher frequencies of active CD11b+ NCM at the baseline (R = −0.6567; p = 0.0031 and R = 0.3862; p = 0.0168, respectively). CD11b NCM, clinical covariates and neurofilament light-chain plasma concentration at the baseline predicted shorter survival in a multivariable and univariate analysis (CD11b NCM—HR: 1.05, CI: 1.01−1.11, p = 0.013. Log rank: above median: 43 months and below median: 21.22 months; p = 0.0022). Blood samples with the highest frequencies of active CD11b+ IM and NCM contained the lowest concentrations of soluble CD11b. Our preliminary data suggest that the levels of active CD11b+ monocytes and NCM in the blood predict different clinical outcomes in ALS.

Objectives: To explore the opportunities and challenges within the health system to facilitate the achievement of universal health coverage (UHC) for people with stroke (PWS) in South Africa (SA)., Setting: SA., Design: Scoping review., Search Methods: We conducted a scoping review of opportunities and challenges to achieve UHC for PWS in SA. Global and Africa-specific databases and grey literature were searched in July 2020. We included studies of all designs that described the healthcare system for PWS. Two frameworks, the Health Systems Dynamics Framework and WHO Framework, were used to map data on governance and regulation, resources, service delivery, context, reorientation of care and community engagement. A narrative approach was used to synthesise results., Results: Fifty-nine articles were included in the review. Over half (n=31, 52.5%) were conducted in Western Cape province and most (n=41, 69.4%) were conducted in urban areas. Studies evaluated a diverse range of health system categories and various outcomes. The most common reported component was service delivery (n=46, 77.9%), and only four studies (6.7%) evaluated governance and regulation. Service delivery factors for stroke care were frequently reported as poor and compounded by context-related limiting factors. Governance and regulations for stroke care in terms of government support, investment in policy, treatment guidelines, resource distribution and commitment to evidence-based solutions were limited. Promising supporting factors included adequately equipped and staffed urban tertiary facilities, the emergence of Stroke units, prompt assessment by health professionals, positive staff attitudes and care, two clinical care guidelines and educational and information resources being available., Conclusion: This review fills a gap in the literature by providing the range of opportunities and challenges to achieve health for all PWS in SA. It highlights some health system areas that show encouraging trends to improve service delivery including comprehensiveness, quality and perceptions of care., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY. Published by BMJ.)

Objective Although sexual problems are common, they are rarely brought up in appointments with general practitioners (GPs). We aimed to assess the barriers that hinder GPs from bringing up sexual health issues and to evaluate the need for education on sexual medicine. Design A web-based questionnaire was used. Setting Four fields were included: A) the self-reported competence in discussing sexual health and treating patients with these issues, B) the barriers to bringing up patients' sexual health problems, C) the source of education on sexual medicine and D) the need for education on sexual medicine. Subjects A random sample of 1000 GPs in Finland (a response rate of 43.5%, n  = 402). Main outcome measures GPs' self-assessed competence in discussing and treating sexual health issues, related barriers to bringing up the topic and the reported need for education. Results The main reasons reported for not bringing up sexual health issues were shortness of the appointment time (85.6%), a lack of knowledge (83.6%) and a lack of experience with sexual medicine (81.8%). The male GPs reported better competence in discussing the issues and treating male patients, whereas the female GPs reported better competence in discussing the issues with female patients. No differences emerged between genders regarding treating female patients. Nearly 90% of the GPs expressed needing more education about sexual medicine. Conclusions Although the GPs reported good competence in discussing sexual health issues with their patients, several barriers to bringing up sexual health issues emerged. Continuing education was desired and could lessen these barriers.Key pointsOnly a few studies have evaluated the competence of general practitioners (GPs) in addressing sexual health issues with their patients.In our study, the GPs reported a high competence in discussing patients' sexual health issues regardless of the patient's gender.However, several barriers to bringing up sexual health issues in appointments emerged.A majority of the GPs expressed a need for continuing education about sexual medicine.

Background: According to the World Health Organization, the worldwide incidence of Down syndrome is one in a thousand live births a year. Of these, it is estimated that 20-60% have congenital heart disease, a factor that hinders breastfeeding. Considering the numerous benefits of breastfeeding, a study verifying this prevalence in children with Down syndrome and congenital heart disease is indispensable, and this is not yet evidenced in the literature. The aim of this study is to verify the prevalence of breastfeeding in children with Down syndrome and congenital heart disease admitted to a referral hospital in cardiology., Methods: Cross-sectional study with 62 patients, aged between 0 and 5 years. Anthropometric variables (weight, height) and data related to breastfeeding were collected. Statistical analysis was performed using the SPSS® version 26.0 statistical software., Results: The prevalence of breastfeeding was of 80.6%, but the median of exclusive breastfeeding was of only 3 days. Only 38.7% received breastfeeding for more than 6 months. The main reasons for interruption were difficulty in sucking and tiredness to breastfeed. Statistical significance was evidenced when comparing the time of exclusive breastfeeding and maintenance with the mother's education, with p = 0.006 and p = 0.041, respectively. No relationship was found between nutritional status and breastfeeding., Conclusions: Despite the high prevalence of breastfeeding, the maintenance time is well below the recommendations. Therefore, further monitoring and promotion of breastfeeding is necessary for this population, given the countless benefits of breast milk., Competing Interests: Declaration of competing interest The authors declare that there are no conflicts of interest associated with the publication of this article., (Copyright © 2021. Published by Elsevier Ltd.)

Introduction: Enhanced recovery protocols (ERP) accelerate recovery and shorten postoperative hospital stay. This increased knowledge of ERPs has also gradually implemented into liver surgery. However, in laparoscopic liver surgery (LLS), the experience of optimized perioperative care protocols is still limited., Methods: We prospectively studied the implementation of multimodal ERP principles to LLS in the first 100 consecutive patients. Opioid-sparing multimodal pain management was applied together with early mobilization already in the postoperative care unit (PACU). Drains and catheters were avoided and per oral intake was initiated promptly. Primary pain control was achieved with iv NSAIDS, low-dose opioid and corticosteroids. Combination of per oral ibuprofen and long-acting tramadol was routinely administered shortly after operation. The multiprofessional adherence to the protocol was also evaluated., Results: Investigated LLS was performed during Aug 2016-Apr 2019. Operations were done due to malignancy in 83 (83%) of cases, mostly for colorectal liver metastases (n = 52, 52%). Forty-eight (48%) of the operated patients were female. Median age was 65 years (range 17-91). The American Society of Anaesthesiologists Physical Status (ASA) classification median was three. Median postoperative hospital stay was 2 days (range 1-8 days). More than seventy percent of patients were discharged by the second postoperative day and nearly ninety percent by the third postoperative day. Complications after surgery were few. The new ERP elements were adopted in most of the cases., Conclusions: ERP was introduced safely and effectively after LLS. The adherence to the ERP was good. Routine discharge 1-2 days after LLS is realistic and achievable.

Rangifer tarandus , the northern species including both reindeer and caribou, is a pillar of northern ecosystems and the lives of northern peoples. As the only domestic cervid, reindeer are important not only to the herders and hunters who presently interact with them, but also to zooarchaeologists and palaeontologists tracing their histories. Unfortunately, limited anatomical information on Rangifer tarandus muscles is available beyond descriptions of the large muscle groups. The lower limb and hoof in particular is poorly documented. This is problematic, as this important body part has the potential to be informative in zooarchaeological analyses of habitual activity, especially in regards to historical animal health, movement, and habitual activity. Better understanding of the hoof can additionally be useful to herders and veterinarians seeking to provide veterinary care for living animals. This study has used dissections and comparisons of the reindeer hoof with other domestic ungulates to document both the common and unique structures in Rangifer tarandus hooves, including the presence and attachment points of these structures. As these structures have proved unique, especially in regards to the dewclaw, it is important that other ungulates not be used exclusively in the analysis of Rangifer tarandus remains., Competing Interests: Conflict of interestNo animals were killed to facilitate this study. The authors have no conflicts of interest to report., (© The Author(s) 2021.)

Background: Spinal pain is one of the leading causes of morbidity globally. There is an increase in the number of children and adolescents who experience spinal pain and the lifetime prevalence of adolescent spinal pain varies between countries. In Africa, one in two adolescents experiences spinal pain and the prevalence is increasing., Objective: This study reports on the knowledge and perspectives of school-attending children, adolescents, teachers, and parents/guardians regarding spinal health., Methods: We conducted a descriptive qualitative case study with an interpretative and phenomenological approach. Data coding, management and analysis was done using ATLAS.ti computer software., Results: Ninety-three participants (66 women and 27 men) were enrolled in the study. The barriers associated with students' spinal health were multifactorial, including low levels of physical activity, dangerous gameplay, sports risks, poor ergonomics, school bags, insufficient knowledge, and pregnancy risks. Participants proposed strategies to improve spinal health including the provision of students' lockers, advice on appropriate school bag types, embedding spinal education in the curriculum, general advocacy for spinal health, and integration of technology in teaching and learning., Conclusion: There is a need for further engagement on school-based spinal health promotion programs that consider local socio-economic, educational, and cultural factors.

Introduction: Stroke is the second most common cause of death after HIV/AIDS and a significant health burden in South Africa. The extent to which universal health coverage (UHC) is achieved for people with stroke in South Africa is unknown. Therefore, a scoping review to explore the opportunities and challenges within the South African health system to facilitate the achievement of UHC for people with stroke is warranted., Methods and Analysis: The scoping review will follow the approach recommended by Levac, Colquhoun and O'Brien, which includes five steps: (1) identifying the research question, (2) identifying relevant studies, (3) selecting the studies, (4) charting the data, and (5) collating, summarising and reporting the results. Health Systems Dynamics Framework and WHO Framework on integrated people-centred health services will be used to map, synthesise and analyse data thematically., Ethics and Dissemination: Ethical approval is not required for this scoping review, as it will only include published and publicly available data. The findings of this review will be published in an open-access, peer-reviewed journal and we will develop an accessible summary of the results for website posting and stakeholder meetings., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY. Published by BMJ.)

Rationale, Aims, and Objectives: Despite research being done on spinal tuberculosis, diagnosing this condition at an early stage remains problematic due to its insidious onset and the varying symptoms being associated. Most individuals present to the health care facility with either simple back pain at an early stage or neurological complications at a later stage, when spinal compression and vertebral collapse have occurred as a result of delayed diagnosis. The prevention of secondary complications is therefore dependent on early recognition and diagnosis. The objective of this review was to identify common clinical patterns in case presentations and develop an evidence-based clinical guidance tool to assist clinicians in the early identification of spinal tuberculosis., Method: A comprehensive literature search was conducted for published spinal tuberculosis case studies, which yielded 28 cases after critical appraisal. Data from the studies were categorized in order to assist with a factor analysis and the development of an evidence framework for screening and diagnosing spinal tuberculosis. An evidence-based clinical guidance tool was then designed from the data obtained., Results: Factors associated with spinal tuberculosis and frequently reported symptoms and physical signs with which the patient could present upon assessment were identified. Options for investigations at primary, secondary, and tertiary levels were also identified., Conclusion: Through the use of an evidence-based clinical guidance tool, the clinician could be guided in the early suspicion and management of individuals with spinal tuberculosis and prevention of secondary complications., (© 2019 John Wiley & Sons, Ltd.)

This study investigated plasma and brain disposition of quetiapine lipid core nanocapsules (QLNC) in naive and schizophrenic (SCZ-like) rats and developed a semimechanistic model to describe changes in both compartments following administration of the drug in solution (FQ) or nanoencapsulated. QLNC (1 mg/ml) presented 166 ± 39 nm, low polydispersity, and high encapsulation (93.0% ± 1.4%). A model was built using experimental data from total and unbound plasma and unbound brain concentrations obtained by microdialysis after administration of single intravenous bolus dose of FQ or QLNC to naive and SCZ-like rats. A two-compartment model was identifiable both in blood and in brain with a bidirectional drug transport across the blood-brain barrier (CL in and CL out ). SCZ-like rats' significant decrease in brain exposure with FQ (decrease in CL in ) was reverted by QLNC, showing that nanocarriers govern quetiapine tissue distribution. Model simulations allowed exploring the potential of LNC for brain delivery. SIGNIFICANCE STATEMENT: A population approach was used to simultaneously model total and unbound plasma and unbound brain quetiapine concentrations allowing for quantification of the rate and extent of the drug's brain distribution following administration of both free drug in solution or as nanoformulation to naive and SCZ-like rats. The model-based approach is useful to better understand the possibilities and limitations of this nanoformulation for drug delivering to the brain, opening the opportunity to use this approach to improve SCZ-treatment-limited response rates., Competing Interests: The authors declare no conflict of interest., (Copyright © 2020 by The American Society for Pharmacology and Experimental Therapeutics.)

The deer ked (Lipoptena cervi) is a harmful ectoparasite that emerged in the reindeer herding area of Finland in 2006. To understand the current range and the intensity of infestations on its novel reindeer host, we studied deer ked pupae collected from reindeer and moose bedding sites and conducted a questionnaire survey among the managers of 18 reindeer herding cooperatives in the southern part of the reindeer herding area. Our study confirmed that the deer ked can survive and successfully reproduce on reindeer through winter and that flying deer keds had been observed in reindeer wintering areas during several autumns in twelve cooperatives. The pupae originating from reindeer were smaller and showed lower hatching rates than the pupae from moose. The present results indicate that the range of the deer ked infestations on reindeer in Finland expanded during the recent 5 years, now reaching 14 cooperatives and bordering an area south of approximately 66° N 25° E in the west and 65° N 29° E east.

Water restriction periods were evaluated in crossbred lambs (n = 32) distributed in one of four treatments: without water restriction, water restriction for 24, 48 and 72 h. The water restriction for 72 h reduced the water and dry matter intakes, body weight at slaughter and hot and cold carcass yields. Water restriction did not affect the weight of the carcass cuts and the chemical composition of the meat. The fatty acid EPA increased and DHA reduced with increasing water restriction period. There was an increasing linear effect for meat shear force, with less force (30.5 N/cm 2 ) for sheep meat without water restriction and higher force (45.8 N/cm 2 ) for those with water restriction for 72 h. The period of 24 h of water restriction was the one that promoted the highest similarities in the characteristics assessed to those in animals receiving water ad libitum. Therefore, water restriction periods should not exceed 24 h for feedlot animals in situations of severe water shortage., (Copyright © 2019. Published by Elsevier Ltd.)

Background: Clinical practice guideline (CPG) activity has escalated internationally in the last 20 years, leading to increasingly sophisticated methods for CPG developers and implementers. Despite this, there remains a lack of practical support for end-users in terms of effectively and efficiently implementing CPG recommendations into local practice. This paper describes South African experiences in implementing international CPG recommendations for best practice stroke rehabilitation into local contexts, using a purpose-build approach., Methods: Composite recommendations were synthesised from 16 international CPGs to address end-user questions about best practice rehabilitation for South African stroke survivors. End-user representatives on the project team included methodologists, policy-makers, clinicians, managers, educators, researchers and stroke survivors. The Adopt-Contextualise-Adapt model was applied as a decision-guide to streamline discussions on endorsement and development of implementation strategies. Where recommendations required contextualisation to address local barriers before they could be effectively implemented, prompts were provided to identify barriers and possible solutions. Where recommendations could not be implemented without additional local evidence (adaptation), options were identified to establish new evidence., Findings: The structured implementation process was efficient in terms of time, effort, resources and problem solving. The process empowered the project team to make practical decisions about local uptake of international recommendations, develop local implementation strategies, and determine who was responsible, for what and when. Different implementation strategies for the same recommendation were identified for different settings, to address different barriers., Conclusion: The South African evidence translation experience could be useful for evidence implementers in other countries, when translating CPG recommendations developed elsewhere, into local practice.

Background: Magnetic resonance imaging (MRI) combined with targeted biopsy (TB) is increasingly used in men with clinically suspected prostate cancer (PCa), but the long acquisition times, high costs, and inter-center/reader variability of routine multiparametric prostate MRI limit its wider adoption., Methods and Findings: The aim was to validate a previously developed unique MRI acquisition and reporting protocol, IMPROD biparametric MRI (bpMRI) (NCT01864135), in men with a clinical suspicion of PCa in a multi-institutional trial (NCT02241122). IMPROD bpMRI has average acquisition time of 15 minutes (no endorectal coil, no intravenous contrast use) and consists of T2-weighted imaging and 3 separate diffusion-weighed imaging acquisitions. Between February 1, 2015, and March 31, 2017, 364 men with a clinical suspicion of PCa were enrolled at 4 institutions in Finland. Men with an equivocal to high suspicion (IMPROD bpMRI Likert score 3-5) of PCa had 2 TBs of up to 2 lesions followed by a systematic biopsy (SB). Men with a low to very low suspicion (IMPROD bpMRI Likert score 1-2) had only SB. All data and protocols are freely available. The primary outcome of the trial was diagnostic accuracy-including overall accuracy, sensitivity, specificity, negative predictive value (NPV), and positive predictive value-of IMPROD bpMRI for clinically significant PCa (SPCa), which was defined as a Gleason score ≥ 3 + 4 (Gleason grade group 2 or higher). In total, 338 (338/364, 93%) prospectively enrolled men completed the trial. The accuracy and NPV of IMPROD bpMRI for SPCa were 70% (113/161) and 95% (71/75) (95% CI 87%-98%), respectively. Restricting the biopsy to men with equivocal to highly suspicious IMPROD bpMRI findings would have resulted in a 22% (75/338) reduction in the number of men undergoing biopsy while missing 4 (3%, 4/146) men with SPCa. The main limitation is uncertainty about the true PCa prevalence in the study cohort, since some of the men may have PCa despite having negative biopsy findings., Conclusions: IMPROD bpMRI demonstrated a high NPV for SPCa in men with a clinical suspicion of PCa in this prospective multi-institutional clinical trial., Trial Registration: ClinicalTrials.gov NCT02241122., Competing Interests: The authors have declared that no competing interests exist.

Low 25-hydroxyvitamin D levels correlate with the prevalence of diabetes; however, the mechanisms remain uncertain. Here, we show that nutritional deprivation-responsive mechanisms regulate vitamin D metabolism. Both fasting and diabetes suppressed hepatic cytochrome P450 (CYP) 2R1, the main vitamin D 25-hydroxylase responsible for the first bioactivation step. Overexpression of coactivator peroxisome proliferator-activated receptor γ coactivator 1-α (PGC-1α), induced physiologically by fasting and pathologically in diabetes, resulted in dramatic downregulation of CYP2R1 in mouse hepatocytes in an estrogen-related receptor α (ERRα)-dependent manner. However, PGC-1α knockout did not prevent fasting-induced suppression of CYP2R1 in the liver, indicating that additional factors contribute to the CYP2R1 repression. Furthermore, glucocorticoid receptor (GR) activation repressed the liver CYP2R1, suggesting GR involvement in the regulation of CYP2R1. GR antagonist mifepristone partially prevented CYP2R1 repression during fasting, suggesting that glucocorticoids and GR contribute to the CYP2R1 repression during fasting. Moreover, fasting upregulated the vitamin D catabolizing CYP24A1 in the kidney through the PGC-1α-ERRα pathway. Our study uncovers a molecular mechanism for vitamin D deficiency in diabetes and reveals a novel negative feedback mechanism that controls crosstalk between energy homeostasis and the vitamin D pathway., (© 2019 by the American Diabetes Association.)

Currently, the first generation of solar panels are reaching their end-of-life, however so far, there is no best available technology (BAT) to deal with solar panel waste in terms of the optimized circular economy of metals. In this brief communication, electro-hydraulic fragmentation (EHF) is explored as an initial conditioning stage of photovoltaic (PV) modules to facilitate the recovery of valuable metals with the main goal to produce liberated fractions that are suitable for the retrieval of materials like Si, Ag, Cu, Sn, Pb, and Al. When compared to traditional crushing, the results suggest that dismantling of PV panels using EHF shows more selectivity by concentrating metals among well-defined particle size fractions. Using this method, the subsequent recovery of metals from PV panels can be achieved in a straightforward manner by simple means like sieving. The fragmentation achievable with EHF technology allowed approximately 99% Cu, 60% Ag, 80% of Pb, Sn and Al total elemental weight within the solar panels to be concentrated solely within the >4 mm size range, whereas high purity (>99%) Si could be found in the fractions between >0.50 mm and <2 mm. To the best of the authors' knowledge, this paper presents for the first time a comparative analysis on the use of EHF technique and conventional crushing for the processing of PV solar panel waste., (Copyright © 2019. Published by Elsevier Ltd.)

Tuberculosis (TB) caused by Mycobacterium tuberculosis remains a deadly infectious disease. The thin pipeline of new drugs for TB, the ineffectiveness in adults of the only vaccine available, i.e. the Bacillus Calmette-Guerin vaccine, and increasing global antimicrobial resistance, has reinvigorated interest in immunotherapies. Nanoparticles (NPs) potentiate the effect of immune modulating compounds (IMC), enabling cell targeting, improved transfection of antigens, enhanced compound stability and provide opportunities for synergistic action, via delivery of multiple IMCs. In this review we describe work performed in the application of NPs towards achieving immune modulation for TB treatment and vaccination. Firstly, we present a comprehensive review of M. tuberculosis and how the bacterium modulates the host immune system. We find that current work suggest great promise of NP based immunotherapeutics as novel treatments and vaccination systems. There is need to intensify research efforts in this field, and rationally design novel NP immunotherapeutics based on current knowledge of the mycobacteriology and immune escape mechanisms employed by M. tuberculosis.

We present new constraints on sub-GeV dark-matter particles scattering off electrons based on 6780.0 kg d of data collected with the DarkSide-50 dual-phase argon time projection chamber. This analysis uses electroluminescence signals due to ionized electrons extracted from the liquid argon target. The detector has a very high trigger probability for these signals, allowing for an analysis threshold of three extracted electrons, or approximately 0.05 keVee. We calculate the expected recoil spectra for dark matter-electron scattering in argon and, under the assumption of momentum-independent scattering, improve upon existing limits from XENON10 for dark-matter particles with masses between 30 and 100  MeV/c^{2}.

We present the results of a search for dark matter weakly interacting massive particles (WIMPs) in the mass range below 20  GeV/c^{2} using a target of low-radioactivity argon with a 6786.0 kg d exposure. The data were obtained using the DarkSide-50 apparatus at Laboratori Nazionali del Gran Sasso. The analysis is based on the ionization signal, for which the DarkSide-50 time projection chamber is fully efficient at 0.1  keVee. The observed rate in the detector at 0.5  keVee is about 1.5  event/keVee/kg/d and is almost entirely accounted for by known background sources. We obtain a 90% C.L. exclusion limit above 1.8  GeV/c^{2} for the spin-independent cross section of dark matter WIMPs on nucleons, extending the exclusion region for dark matter below previous limits in the range 1.8-6  GeV/c^{2}.

Objective: Patterns of benzodiazepine (BZD) use and long-term use among young adults are not well known. Our aim was to study trends in BZD use and long-term use among 18-25-year-old young adults by gender and active substance in a nationwide retrospective longitudinal register-based setting., Methods: All Finns aged 18-25 years with reimbursed purchases of BZDs in 2006-2014 recorded to the Finnish Prescription Register were included. Annual prevalence rates of BZD use and long-term use among young adults were reported overall, according to gender, drug group (anxiolytic or hypnotic), and active substance. Long-term use of BZDs was defined as purchasing ≥180 Defined Daily Doses (DDDs) in at least two drug purchases during a calendar year., Results: Overall prevalence of BZD use among young adults decreased from 24.0 to 18.8 users per 1000 inhabitants in 2006-2014. Prevalence of long-term use decreased from 5.5 to 3.3 users per 1000 inhabitants. Overall BZD use was higher among females, whereas long-term use was more common among males. Use of anxiolytics was more common than use of hypnotics. Oxazepam, alprazolam, zopiclone, and zolpidem were the most used BZDs, whereas alprazolam and clonazepam were the substances with most long-term use. The use and long-term use of BZDs have decreased annually since 2008 among Finnish young adults. Further research is needed to investigate the reasons behind the decline.

Background and Aims: Pain assessment in intensive care is challenging, especially when the patients are sedated. Sedated patients who cannot communicate verbally are at risk of suffering from pain that remains unnoticed without careful pain assessment. Some tools have been developed for use with sedated patients. The Behavioral Pain Scale (BPS), the Critical-Care Pain Observation Tool (CPOT) and the Nonverbal Adult Pain Assessment Scale (NVPS) have shown promising psychometric qualities. We translated and culturally adapted these three tools for the Finnish intensive care environment. The objective of this feasibility study was to test the reliability of the three pain assessment tools translated into Finnish for use with sedated intensive care patients., Methods: Six sedated intensive care patients were videorecorded while they underwent two procedures: an endotracheal suctioning was the nociceptive procedure, and the non-nociceptive treatment was creaming of the feet. Eight experts assessed the patients' pain by observing video recordings. They assessed the pain using four instruments: the BPS, the CPOT and the NVPS, and the Numeric Rating Scale (NRS) served as a control instrument. Each expert assessed the patients' pain at five measurement points: (1) right before the procedure, (2) during the endotracheal suctioning, (3) during rest (4) during the creaming of the feet, and (5) after 20 min of rest. Internal consistency and inter-rater reliability of the tools were evaluated. After 6 months, the video recordings were evaluated for testing the test-retest reliability., Results: Using the BPS, the CPOT, the NVPS and the NRS, 960 assessments were obtained. Internal consistency with Cronbach's alpha coefficient varied greatly with all the instruments. The lowest values were seen at those measurement points where the pain scores were 0. The highest scores were achieved after the endotracheal suctioning at rest: for the BPS, the score was 0.86; for the CPOT, 0.96; and for the NVPS, 0.90. The inter-rater reliability using the Shrout-Fleiss intraclass correlation coefficient (ICC) tests showed the best results after the painful procedure and during the creaming. The scores were slightly lower for the BPS compared to the CPOT and the NVPS. The test-retest results using the Bland-Altman plots show that all instruments gave similar results., Conclusions: To our knowledge, this is the first time all three behavioral pain assessment tools have been evaluated in the same study in a language other than English or French. All three tools had good internal consistency, but it was better for the CPOT and the NVPS compared to the BPS. The inter-rater reliability was best for the NVPS. The test-retest reliability was strongest for the CPOT. The three tools proved to be reliable for further testing in clinical use., Implications: There is a need for feasible, valid and reliable pain assessment tools for pain assessment of sedated ICU patients in Finland. This was the first time the psychometric properties of these tools were tested in Finnish use. Based on the results, all three instruments could be tested further in clinical use for sedated ICU patients in Finland.

Aim: To evaluate the impact of video education on critical care nurses' knowledge and skills in using a behavioural pain assessment tool for intensive care patients and to explore the nurses' experiences with video education., Methods: Forty-eight nurses in one intensive care unit watched an educational video on the use of the Critical-Care Pain Observation Tool, then assessed pain in two patients with the tool and took a knowledge test. The researcher made parallel pain assessments. Interrater reliability of patients' pain assessment between nurses and the researcher was determined to examine nurses' skills in using the tool after education. Twenty nurses were interviewed about their experiences with the video education. Interviews were analysed with deductive thematic analysis., Results: The knowledge test scores indicated that the nurses learned the principles of how to use the tool. The interrater reliability of pain assessments reached a moderate level of agreement during the painful procedure, with a weighted kappa coefficient value of 0.48, CL [0.37, 0.58]. The nurses perceived video education positively, but requested additional interaction., Conclusions: Video education is useful in teaching the principles of using a pain assessment tool. Additional clinical training is required for nurses to reach adequate skills in using the tool., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

Background: The prevalence of overweight in children with CHD is about 26.9%. Increase in adipose tissue is related to the secretion of proinflammatory markers such as C-reactive protein. Assuming that children with CHD are exposed to other inherent risk factors for heart disease, our objective was to evaluate the correlation between levels of C-reactive protein and body mass index in children and adolescents with CHD., Methods: A cross-sectional study with 377 children and adolescents with CHD in a clinical setting of a reference hospital was carried out. C-reactive protein data were collected after 12 hours of fasting. Nutritional status was classified according to body mass index. The patients were divided into three groups: cyanotic, acyanotic, and minimal heart defects (controls)., Results: The mean age was 9.9±4.2 years, and 53.6% of the sample included males. The cyanotic group represented 22.3%, acyanotic 42.2%, and minimal defects 35.5% of the sample. The average body mass index percentile was 57.23±32.06. The median values of C-reactive protein were as follows: cyanotic 0.340, acyanotic with clinical repercussion 0.203, and minimal defects 0.128. There was a significant difference between the minimal defects and the cyanotic groups (p=0.023). There was a significant correlation between C-reactive protein and body mass index percentile (r=0.293, p<0.01). C-reactive protein levels were higher in girls (p=0.034). There were no significant correlations between C-reactive protein and age or birth weight., Conclusion: The correlation between body mass index percentile and C-reactive protein was confirmed in this population. The prevention of overweight is paramount to avoid overlapping modifiable risk factors to those already inherent to the CHD.