Airway decision making in major head and neck surgery: Irish multicenter, multidisciplinary recommendations.

Major head and neck surgery poses a threat to perioperative airway patency. Adverse airway events are associated with significant morbidity, potentially leading to hypoxic brain injury and even death. Following a review of the literature, recommendations regarding airway management in head and neck surgery were developed with multicenter, multidisciplinary agreement among all Irish head and neck units. Immediate extubation is appropriate in many cases where there is a low risk of adverse airway events. Where a prolonged definitive airway is required, elective tracheostomy provides increased airway security postoperatively while delayed extubation may be appropriate in select cases to reduce postoperative morbidity. Local institutional protocols should be developed to care for a tracheostomy once inserted. We provide guidance on decision making surrounding airway management at time of head and neck surgery. All decisions should be agreed between the operating, anesthetic, and critical care teams.

Language Learning for People Living with Dementia and Their Caregivers: Feasibility and the Quality of Experience.

BACKGROUND: A body of research from around the world has reported positive effects of bilingualism on cognitive ageing and dementia. However, little is known about whether foreign language learning could be applied as an intervention for people already living with dementia. Yet, before it is possible to determine the efficacy of language courses as an intervention for people living with dementia (PLWD), it is necessary to establish whether such an intervention is feasible. Our study explored this possibility. METHODS: We conducted an exploratory study to examine the feasibility and tolerability of 2-week Italian beginner courses for PLWD in early stages and their family carers in two Scottish Dementia Resource Centres (DRCs). The courses were delivered by trained tutors from Lingo Flamingo, a social enterprise specialising in language teaching for older learners and learners with dementia. Twelve PLWD and seven carers participated in the study. Focus groups preceded and followed the courses. Additional post-course open interviews with the DRC managers were conducted, with a follow-up via telephone approximately one year later. RESULTS: Qualitative content analysis resulted in 12 themes, 5 reflected in the interview schedule and 7 arising from the focus groups and interviews. Overall, the courses were perceived positively by PLWD, carers, and DRC managers, although a few logistically and linguistically challenging aspects were also mentioned. The courses were found to positively impact both the individual by increasing self-esteem and producing a sense of accomplishment as well as the group by creating a sense of community. Notably, no adverse effects (in particular no confusion or frustration) were reported. CONCLUSION: The positive outcomes of our study open a novel avenue for future research to explore foreign language training in dementia as an intervention and its implications.

Partial Thyroidectomy With Incidental Metastatic Lymph Nodes.

Importance: The need for completion thyroidectomy in patients with incidental metastatic lymph nodes after partial thyroidectomy is unclear. Objective: To investigate the outcomes of patients with incidental metastatic lymph nodes following partial thyroidectomy. Design, Setting, and Participants: A retrospective review of a prospectively maintained thyroid cancer database from 1985 to 2015 was carried out at a head and neck surgery practice at a tertiary referral cancer center. A total of 74 patients who underwent thyroid lobectomy or thyroid isthmusectomy between 1985 and 2015 and were found to have incidental metastatic lymph nodes on final pathologic analysis and were selected to be observed without immediate completion thyroidectomy were included. A separate group of additional 11 patients who underwent immediate completion thyroidectomy was also identified and reviewed. Main Outcome and Measure: Analysis took place from February to May 2022. Recurrence-free survival outcomes of patients found to have incidental metastatic lymph nodes on final pathologic analysis following partial thyroidectomy with no immediate completion thyroidectomy. Results: A total of 74 patients were observed, with a median (IQR) age of 39 (28-49) years; 44 (59%) were women. Sixty-four patients underwent thyroid lobectomy and 10 patients had isthmusectomy. Classic papillary thyroid carcinoma was the most common histologic type (34 [46%]). Vascular invasion and microscopic extrathyroidal extension were present in 11 patients (16%) and 22 patients (30%), respectively. Positive margins were identified in 5 patients (7.8%). Size of metastatic lymph nodes ranged between 0.07 cm and 1.2 cm. No extranodal extension was reported. A total of 52 patients (70%) were classified as intermediate risk for recurrence based on the American Thyroid Association risk stratification system. The median (IQR) follow up was 48.15 (15.4-86.1) months, during which only 1 patient had a regional recurrence. Another patient underwent delayed completion thyroidectomy for a contralateral lobe malignant abnormality. Recurrence-free survival, disease-specific survival, and overall survival were 97.4%, 100%, and 96.2%, respectively. A separate group of 11 patients who underwent immediate completion thyroidectomy were reviewed. These patients were more likely to have tall-cell papillary thyroid carcinoma (6 [55%] vs 13 [18%]), multifocality (9 [82%] vs 28 [41%]), microscopic extrathyroidal extension (8 [73%] vs 22 [30%]), and positive margins (3 [30%] vs 5 [7.8%]) compared with patients who were under observation only. Conclusion and Relevance: Completion thyroidectomy may not be necessary in appropriately selected patients who are found to have incidental metastatic lymph nodes (N1a) after partial thyroidectomy for localized well-differentiated thyroid cancer.

Manganese Exacerbates Seasonal Health Declines in a Suicidally Breeding Mammal.

Reproductive costs must be balanced with survival to maximize lifetime reproductive rates; however, some organisms invest in a single, suicidal bout of breeding known as semelparity. The northern quoll (Dasyurus hallucatus) is an endangered marsupial in which males, but not females, are semelparous. Northern quolls living near mining sites on Groote Eylandt, Northern Territory, Australia, accumulate manganese (Mn) in their brains, testes, and hair, and elevated Mn impacts motor performance. Whether Mn is associated with other health declines is yet unknown. In the present study we show that male and female northern quolls with higher Mn accumulation had a 20% reduction in immune function and a trend toward reduced cortisol concentrations in hair. The telomere lengths of male quolls did not change pre- to postbreeding, but those with higher Mn levels had longer telomeres; in contrast, the telomeres of females shortened during the breeding season but recovered between the first year and second year of breeding. In addition, the telomeres of quolls that were recaptured declined at significantly higher rates in quolls with higher Mn between prebreeding, breeding, and/or postbreeding seasons. Future research should determine whether changes in cortisol, immune function, or telomere length affect reproductive output or survival-particularly for semelparous males. Environ Toxicol Chem 2024;43:74-86. © 2023 The Authors. Environmental Toxicology and Chemistry published by Wiley Periodicals LLC on behalf of SETAC.

The role of surgery for anaplastic thyroid carcinoma in the era of targeted therapeutics: A scoping review.

Background: Questions exist regarding patient selection for surgery in anaplastic thyroid carcinoma (ATC), particularly with the advent of neoadjuvant-targeted therapeutics. The present scoping review sought to evaluate what extent of surgical resection should be performed in ATC. Methods: A scoping review was carried out in accordance with Joanna Briggs Institute and the preferred reporting items for systematic reviews and meta-analyses extension for scoping reviews (PRISMA-ScR) protocols. Included studies were required to provide clear description of the surgery performed for ATC. Results: The final search identified 6901 articles. Ultimately only 15 articles including 1484 patients met inclusion criteria. A total of 765 patients (51.5%) underwent attempted curative intent surgery. The approach to resection of adjacent tissues varied between studies. Eight studies considered laryngeal ± pharyngeal resection (8/15, 53.3%), eight studies (53.3%) considered tracheal resection and again eight studies (53.3%) considered esophageal resection. More extensive resections increased morbidity without improving overall survival (OS) (<9 months in the 12 studies using a combination of surgery and chemoradiotherapy). In the three studies utilizing targeted therapy in addition to surgery, OS was notably improved while surgical resection following neoadjuvant therapy was less extensive. Conclusions: There is no clear agreement in the literature regarding the limits of surgical resection in locoregionally advanced ATC. A definition of surgically resectable disease will be required to guide surgical decision making in ATC, particularly with the potential to reduce tumor burden using neoadjuvant targeted treatment in suitable patients. Level of evidence: III.

Pre-cleaning of hair is not beneficial in LA-ICP-MS studies of chronic metal exposure.

Chronic exposure to toxic metals is a serious global health concern. However, population-wide biomonitoring is costly and carries several sampling constraints. Though hair sampling can be a useful way to assess environmental exposure, external contamination is a long-standing concern, and a pre-cleaning step prior to metal quantification has long been recommended despite a lack of evidence for its efficacy. In this study, we quantified the spatial distribution of 16 elements in unwashed human hair samples using Laser Ablation Inductively Coupled Plasma Mass Spectrometry (LA-ICP-MS), then tested how two common pre-cleaning treatments (Triton-ethanol, Triton-nitric acid) affected metal content in external and interior layers of hair using LA-ICP-MS. We show that elements differ in their spatial distribution across hair and that pre-cleaning is not consistent in its effect on element concentrations and decreases interior concentrations of some elements. We demonstrate that differences among individuals can be quantified reliably with LA-ICP-MS analysis of interior concentrations of unwashed hair. Our study tests the widespread notion that pre-cleaning is essential in analyses of hair for environmental exposure to metals, and examines the benefits of a unified approach to analysis of metals in hair using LA-ICP-MS.

Resting disparity in quoll semelparity: examining the sex-linked behaviours of wild roaming northern quolls (Dasyurus hallucatus) during breeding season.

Semelparity is a breeding strategy whereby an individual invests large amounts of resources into a single breeding season, leading to the death of the individual. Male northern quolls (Dasyurus hallucatus) are the largest known mammal to experience a post-breeding die-off; however, the cause of their death is unknown, dissimilar from causes in other semelparous dasyurids. To identify potential differences between male northern quolls that breed once, and females that can breed for up to four seasons, the behaviours, activity budgets, speeds and distances travelled were examined. Northern quolls were captured on Groote Eylandt off the coast of the Northern Territory, Australia, and were fitted with accelerometers. A machine learning algorithm (Self-organizing Map) was trained on more than 76 h of recorded footage of quoll behaviours and used to predict behaviours in 42 days of data from wild roaming quolls (7M : 6F). Male northern quolls were more active (male 1.27 g, s.d. = 0.41; female 1.18 g, s.d. = 0.36), spent more time walking (13.09% male: 8.93% female) and engaged in less lying/resting behaviour than female northern quolls (7.67% male: 23.65% female). Reduced resting behaviour among males could explain the post-breeding death as the deterioration in appearance reflects that reported for sleep-deprived rodents.

Surgical management of T1/T2 node-negative papillary thyroid cancer with tall cell histology: Is lobectomy enough?

BACKGROUND: The tall cell variant of papillary thyroid carcinoma has traditionally been treated more aggressively than classic papillary thyroid carcinoma. However, this may not be justified in patients with T1/T2 tall cell variant node-negative tumors. METHODS: We evaluated well-differentiated thyroid cancers treated surgically between 1985 and 2015 at our institution. We compared patients undergoing lobectomy for node-negative T1/T2 tall cell variant tumors with the same cohort with classic papillary thyroid carcinoma. Patients who underwent early planned completion thyroidectomy were excluded. Tall cell variant tumors were defined as those with ≥30% tall cells. Survival and recurrence outcomes were determined by the Kaplan-Meier method and groups compared using the log-rank test. RESULTS: Thyroid lobectomy was performed for T1/T2 N0X disease in 70 (15%) tall cell cases and 429 (23%) classic papillary thyroid carcinoma cases. There was no significant difference in 10-year overall survival (P = .56) or locoregional recurrence-free probability (P = .52). Disease-specific survival and local or central nodal recurrence-free probability were 100% in both groups. In 9 papillary thyroid carcinoma cases, subsequent contralateral lobe tumors developed, and in 5, lateral neck metastases developed. No recurrences were seen in the tall cell group. CONCLUSION: T1 node-negative tumors with tall cell histology can be satisfactorily managed with thyroid lobectomy, with equivalent oncological outcomes to classic papillary thyroid carcinoma.

Identifying the best strategy for soccer penalty success: A predictive model for optimising behavioural and biomechanical trade-offs.

Success in a soccer penalty can be the difference between winning and losing matches. The outcome is determined by a complex interaction between the shooter and goalkeeper, whose performances are constrained by biomechanical trade-offs. To overcome these performance constraints, each player has a range of available strategies. Shooters can kick at different speeds, affecting accuracy, while goalkeepers can move at various times (leave-times), affecting the time available to move and the probability they move in the correct direction. Previous models of penalty success ignore such trade-offs and how they interact to influence the outcome. Here, we present a model that accounts for shooting inaccuracy to predict the probability of success for all shooting strategies, defined as any combination of: shot speed, position where the shooter aims, shooter footedness, and kicking technique (side-foot or instep). To estimate the probability of success each shooting strategy is matched against all possible goalkeeper leave-times, considering the probability each leave-time is chosen. We test the model against an average goalkeeper and a goalkeeper who tends to move later. Against the average goalkeeper, aiming on the ground toward the centre of the goal is optimal; however, against a late moving goalkeeper, aiming on the ground to the extremities of the goal is effective, with the optimal target in the horizontal dimension dependent on shot speed, kick technique, and footedness. Coaches could use this model to identify their best penalty takers and each players' optimal shooting strategy against either the average goalkeeper or a specific goalkeeper.

Age- and size-corrected kicking speed and accuracy in elite junior soccer players.

Kicking powerfully and accurately is essential in soccer, and players who kick proficiently with both feet are highly sought after. Assessing performance in youth players is often confounded by more physically developed players outperforming their smaller peers. To alleviate such bias, we present a testing protocol and normative data developed with an elite Brazilian soccer academy that controls for players' age and size to assess kick performance with both feet. We measured kick speed and kick accuracy of 178 players and recorded their age (10-20 years), height, and mass. Combining age, height, and mass into an age and size index (ASI), we developed equations describing the relationship between ASI and performance. To determine the underlying predictors of performance, we also measured sprint ability and soccer-specific motor control of each foot with ball dribbling tasks. Kicking speed with the dominant foot was predicted by ASI, sprint speed, and motor control of the nondominant foot, while kicking speed with the nondominant foot was predicted by ASI and motor control of the nondominant foot. Kick accuracy with each foot was predicted by ASI and motor control of the corresponding foot. To improve kicking performance, we suggest training programs focus on motor control.

Peripartal treatment with low-dose sertraline accelerates mammary gland involution and has minimal effects on maternal and offspring bone.

Women mobilize up to 10% of their bone mass during lactation to provide milk calcium. About 8%-13% of mothers use selective serotonin reuptake inhibitors (SSRI) to treat peripartum depression, but SSRIs independently decrease bone mass. Previously, peripartal use of the SSRI fluoxetine reduced maternal bone mass sustained post-weaning and reduced offspring bone length. To determine whether these effects were fluoxetine-specific or consistent across SSRI compounds, we examined maternal and offspring bone health using the most prescribed SSRI, sertraline. C57BL/6 mice were given 10 mg/kg/day sertraline, from the beginning of pregnancy through the end of lactation. Simultaneously, we treated nulliparous females on the same days as the primiparous groups, resulting in age-matched nulliparous groups. Dams were euthanized at lactation day 10 (peak lactation, n = 7 vehicle; n = 9 sertraline), lactation day 21 (weaning, n = 9 vehicle; n = 9 sertraline), or 3m post-weaning (n = 10 vehicle; n = 10 sertraline) for analysis. Offspring were euthanized at peak lactation or weaning for analysis. We determined that peripartum sertraline treatment decreased maternal circulating calcium concentrations across the treatment period, which was also seen in nulliparous treated females. Sertraline reduced the bone formation marker, procollagen 1 intact N-terminal propeptide, and tended to reduce maternal BV/TV at 3m post-weaning but did not impact maternal or offspring bone health otherwise. Similarly, sertraline did not reduce nulliparous female bone mass. However, sertraline reduced immunofluorescence staining of the tight junction protein, zona occludens in the mammary gland, and altered alveoli morphology, suggesting sertraline may accelerate mammary gland involution. These findings indicate that peripartum sertraline treatment may be a safer SSRI for maternal and offspring bone rather than fluoxetine.

Machine learning accurately predicts the multivariate performance phenotype from morphology in lizards.

Completing the genotype-to-phenotype map requires rigorous measurement of the entire multivariate organismal phenotype. However, phenotyping on a large scale is not feasible for many kinds of traits, resulting in missing data that can also cause problems for comparative analyses and the assessment of evolutionary trends across species. Measuring the multivariate performance phenotype is especially logistically challenging, and our ability to predict several performance traits from a given morphology is consequently poor. We developed a machine learning model to accurately estimate multivariate performance data from morphology alone by training it on a dataset containing performance and morphology data from 68 lizard species. Our final, stacked model predicts missing performance data accurately at the level of the individual from simple morphological measures. This model performed exceptionally well, even for performance traits that were missing values for >90% of the sampled individuals. Furthermore, incorporating phylogeny did not improve model fit, indicating that the phenotypic data alone preserved sufficient information to predict the performance based on morphological information. This approach can both significantly increase our understanding of performance evolution and act as a bridge to incorporate performance into future work on phenomics.

Effect of Low and High Doses of Two Selective Serotonin Reuptake Inhibitors on Pregnancy Outcomes and Neonatal Mortality.

Selective serotonin reuptake inhibitors (SSRI) are the most common antidepressant used by pregnant women; however, they have been associated with adverse pregnancy outcomes and perinatal morbidity in pregnant women and animal models. We investigated the effects of two SSRI, fluoxetine and sertraline, on pregnancy and neonatal outcomes in mice. Wild-type mice were treated daily with low and high doses of fluoxetine (2 and 20 mg/kg) and sertraline (10 and 20 mg/kg) from the day of detection of a vaginal plug until the end of lactation (21 days postpartum). Pregnancy rate was decreased only in the high dose of fluoxetine group. Maternal weight gain was reduced in the groups receiving the high dose of each drug. Number of pups born was decreased in the high dose of fluoxetine and low and high doses of sertraline while the number of pups weaned was decreased in all SSRI-treated groups corresponding to increased neonatal mortality in all SSRI-treated groups. In conclusion, there was a dose-dependent effect of SSRI on pregnancy and neonatal outcomes in a non-depressed mouse model. However, the distinct placental transfer of each drug suggests that the effects of SSRI on pup mortality may be mediated by SSRI-induced placental insufficiency rather than a direct toxic effect on neonatal development and mortality.

Analysis of Outcomes of Pharyngo-laryngo-esophagectomy and Reconstruction with Longitudinal Comparison in a Single Institution.

Advanced hypopharyngeal tumours present complex clinical challenges, and where resection is attempted, there is a requirement for major reconstruction. Despite advances in surgical technique, outcomes remain poor for this patient group, and optimum treatment has yet to be established. We aimed to assess the treatment and outcomes of patients in our institution in the context of previous studies. All patients from 2008 to 2018 who underwent surgical management for hypopharyngeal tumours with pharyngo-laryngo-esophagectomy and flap-based reconstruction were included in the study. Demographic and outcome data were collected, and patient-reported outcomes were solicited from surviving patients using the EORTC QLQ H&N 43 questionnaire. Thirty patients were assessed, in which 12 had gastric pull-ups, 16 had free jejunum flaps, and 2 had free anterolateral thigh flaps. There was a 38% five-year survival rate. Overall, the rates of stricture (10.7%) and fistula (7.1%) were low. The majority of patients (53.6%) returned to a normal diet within three months with a soft or puree diet in 35.7% of patients. Some form of speech was possible in 92.9% of patients. The average questionnaire score for surviving patients was 87.3, with good outcomes related to eating and swallowing, but poorer outcomes for speech and communication. This study showed that outcomes for patients receiving complex reconstruction following hypopharyngeal tumour resection are improving over time. There is still scope for improvement of patient outcomes and refinement of optimum surgical management strategies.

Cytokeratin 7 and 19 expression in oropharyngeal and oral squamous cell carcinoma.

PURPOSE: The precise etiopathogenesis of human papillomavirus (HPV)-related oropharyngeal squamous cell carcinoma (OPSCC), and reasons for predilection for crypt epithelium, remain uncertain. The purpose of this study is to investigate the interaction between HPV and specific cytokeratins 7 (CK7) and 19 (CK19) in crypt epithelium. METHODS: This is a retrospective cohort study of patients presenting between 1999 and 2015 at a tertiary referral center. CK7 and CK19 positivity and H Scores were determined by immunohistochemistry. Disease-specific and overall survival rates were analyzed. RESULTS: There were 253 patients presenting with OPSCC (134), squamous cell carcinoma (SCC) of unknown primary site (22), and oral tongue SCC (97). Primary tumor CK7 and CK19 positivity and H Scores were significantly higher in HPV-positive OPSCC than HPV-negative OPSCC and oral tongue SCC. Higher CK19 Scores, but not CK7 Scores, were also seen in regional metastases from HPV-positive OPSCC than other sites. No impact on disease-specific or overall survival was identified on multivariate analysis. CONCLUSION: The increased expression of CK7 and CK19 in HPV-positive OPSCC compared to HPV-negative disease supports the theory for a role for these cytokeratins in the etiopathogenesis of HPV-related OPSCC.

Low-dose oral misoprostol for induction of labour.

BACKGROUND: Misoprostol given orally is a commonly used labour induction method. Our Cochrane Review is restricted to studies with low-dose misoprostol (initially ≤ 50 µg), as higher doses pose unacceptably high risks of uterine hyperstimulation. OBJECTIVES: To assess the efficacy and safety of low-dose oral misoprostol for labour induction in women with a viable fetus in the third trimester of pregnancy. SEARCH METHODS: We searched Cochrane Pregnancy and Childbirth's Trials Register, ClinicalTrials.gov,  the WHO International Clinical Trials Registry Platform (14 February 2021) and reference lists of retrieved studies. SELECTION CRITERIA: Randomised trials comparing low-dose oral misoprostol (initial dose ≤ 50 µg) versus placebo, vaginal dinoprostone, vaginal misoprostol, oxytocin, or mechanical methods; or comparing oral misoprostol protocols (one- to two-hourly versus four- to six-hourly; 20 µg to 25 µg versus 50 µg; or 20 µg hourly titrated versus 25 µg two-hourly static). DATA COLLECTION AND ANALYSIS: Using Covidence, two review authors independently screened reports, extracted trial data, and performed quality assessments. Our primary outcomes were vaginal birth within 24 hours, caesarean section, and hyperstimulation with foetal heart changes. MAIN RESULTS: We included 61 trials involving 20,026 women. GRADE assessments ranged from moderate- to very low-certainty evidence, with downgrading decisions based on imprecision, inconsistency, and study limitations. Oral misoprostol versus placebo/no treatment (four trials; 594 women) Oral misoprostol may make little to no difference in the rate of caesarean section (risk ratio (RR) 0.81, 95% confidence interval (CI) 0.59 to 1.11; 4 trials; 594 women; moderate-certainty evidence), while its effect on uterine hyperstimulation with foetal heart rate changes is uncertain (RR 5.15, 95% CI 0.25 to 105.31; 3 trials; 495 women; very low-certainty evidence). Vaginal births within 24 hours was not reported. In all trials, oxytocin could be commenced after 12 to 24 hours and all women had pre-labour ruptured membranes. Oral misoprostol versus vaginal dinoprostone (13 trials; 9676 women) Oral misoprostol probably results in fewer caesarean sections (RR 0.84, 95% CI 0.78 to 0.90; 13 trials, 9676 women; moderate-certainty evidence). Subgroup analysis indicated that 10 µg to 25 µg (RR 0.80, 95% CI 0.74 to 0.87; 9 trials; 8652 women) may differ from 50 µg (RR 1.10, 95% CI 0.91 to 1.34; 4 trials; 1024 women) for caesarean section. Oral misoprostol may decrease vaginal births within 24 hours (RR 0.93, 95% CI 0.87 to 1.00; 10 trials; 8983 women; low-certainty evidence) and hyperstimulation with foetal heart rate changes (RR 0.49, 95% CI 0.40 to 0.59; 11 trials; 9084 women; low-certainty evidence). Oral misoprostol versus vaginal misoprostol (33 trials; 6110 women) Oral use may result in fewer vaginal births within 24 hours (average RR 0.81, 95% CI 0.68 to 0.95; 16 trials, 3451 women; low-certainty evidence), and less hyperstimulation with foetal heart rate changes (RR 0.69, 95% CI 0.53 to 0.92, 25 trials, 4857 women, low-certainty evidence), with subgroup analysis suggesting that 10 µg to 25 µg orally (RR 0.28, 95% CI 0.14 to 0.57; 6 trials, 957 women) may be superior to 50 µg orally (RR 0.82, 95% CI 0.61 to 1.11; 19 trials; 3900 women). Oral misoprostol probably does not increase caesarean sections overall (average RR 1.00, 95% CI 0.86 to 1.16; 32 trials; 5914 women; low-certainty evidence) but likely results in fewer caesareans for foetal distress (RR 0.74, 95% CI 0.55 to 0.99; 24 trials, 4775 women). Oral misoprostol versus intravenous oxytocin (6 trials; 737 women, 200 with ruptured membranes) Misoprostol may make little or no difference to vaginal births within 24 hours (RR 1.12, 95% CI 0.95 to 1.33; 3 trials; 466 women; low-certainty evidence), but probably results in fewer caesarean sections (RR 0.67, 95% CI 0.50 to 0.90; 6 trials; 737 women; moderate-certainty evidence). The effect on hyperstimulation with foetal heart rate changes is uncertain (RR 0.66, 95% CI 0.19 to 2.26; 3 trials, 331 women; very low-certainty evidence). Oral misoprostol versus mechanical methods (6 trials; 2993 women) Six trials compared oral misoprostol to transcervical Foley catheter. Misoprostol may increase vaginal birth within 24 hours (RR 1.32, 95% CI 0.98 to 1.79; 4 trials; 1044 women; low-certainty evidence), and probably reduces the risk of caesarean section (RR 0.84, 95% CI 0.75 to 0.95; 6 trials; 2993 women; moderate-certainty evidence). There may be little or no difference in hyperstimulation with foetal heart rate changes (RR 1.31, 95% CI 0.78 to 2.21; 4 trials; 2828 women; low-certainty evidence). Oral misoprostol one- to two-hourly versus four- to six-hourly (1 trial; 64 women) The evidence on hourly titration was very uncertain due to the low numbers reported. Oral misoprostol 20 µg hourly titrated versus 25 µg two-hourly static (2 trials; 296 women) The difference in regimen may have little or no effect on the rate of vaginal births in 24 hours (RR 0.97, 95% CI 0.80 to 1.16; low-certainty evidence). The evidence is of very low certainty for all other reported outcomes. AUTHORS' CONCLUSIONS: Low-dose oral misoprostol is probably associated with fewer caesarean sections (and therefore more vaginal births) than vaginal dinoprostone, and lower rates of hyperstimulation with foetal heart rate changes. However, time to birth may be increased, as seen by a reduced number of vaginal births within 24 hours. Compared to transcervical Foley catheter, low-dose oral misoprostol is associated with fewer caesarean sections, but equivalent rates of hyperstimulation. Low-dose misoprostol given orally rather than vaginally is probably associated with similar rates of vaginal birth, although rates may be lower within the first 24 hours. However, there is likely less hyperstimulation with foetal heart changes, and fewer caesarean sections performed due to foetal distress. The best available evidence suggests that low-dose oral misoprostol probably has many benefits over other methods for labour induction. This review supports the use of low-dose oral misoprostol for induction of labour, and demonstrates the lower risks of hyperstimulation than when misoprostol is given vaginally. More trials are needed to establish the optimum oral misoprostol regimen, but these findings suggest that a starting dose of 25 µg may offer a good balance of efficacy and safety.

Playing the long game: Exploring the phenomenon of dementia-friendly golf.

As individuals age, participation in previously accessible leisure activities can be compromised through diminished capabilities and negative societal expectations. This study investigates the unexplored accessibility of golf for older people with dementia using interviews and observations of Scottish participants in social enterprise-led golfing activities. The resulting thematic analysis concluded that golf is an accessible activity for people living with dementia, and continued participation generates social connectedness and enhances well-being. However, there remain social barriers to participation including societal stigma surrounding the perceived abilities of people living with dementia and the perception of golf as a middle-class and male-dominated sport.

Simple and reliable protocol for identifying talented junior players in team sports using small-sided games.

We designed and tested a protocol for measuring the performance of individuals in small-sided soccer games. We tested our protocol on three different groups of youth players from elite Brazilian football academies. Players in each group played a series of 3v3 games, in which individuals were randomly assigned into new teams and against new opponents for each game. We calculated each individual's average individual goals scored, goals scored by teammates, goals conceded, and net team goals per game. Our protocol was consistent across days and repeatable across groups, with intraclass correlation coefficients (ICCs) of 0.57-0.69 for average net goals per game across testing days. Players could achieve high success by scoring goals or ensuring their team concede few goals. We also calculated the first and second dimension of a principal component analysis based on each player's number of goals scored, goals scored by teammates, and number of goals conceded per game. Players that were overall high performers had higher PC1 scores, while PC2 scores represented the type of contribution made by a player to overall performance. Positive PC2 values were indicative of high number of individual goals while negative values were associated with more goals from teammates and fewer conceded goals. Our design allows coaches and scouts to easily collect a robust metric of individual performance using randomly designed, small-sided games. We also provide simulations that allow one to apply our methodology for individual talent identification to other small-sided games in any team sport.

Sexual dimorphism in immunometabolism and autoimmunity: Impact on personalized medicine.

Immune cells play essential roles in metabolic homeostasis and thus, undergo analogous changes in normal physiology (e.g., puberty and pregnancy) and in various metabolic and immune diseases. An essential component of this close relationship between the two is sex differences. Many autoimmune diseases, such as systemic lupus erythematous and multiple sclerosis, feature strikingly increased prevalence in females, whereas in contrast, infectious diseases, such as Ebola and Middle East Respiratory Syndrome, affect more men than women. Therefore, there are fundamental aspects of metabolic homeostasis and immune functions that are regulated differently in males and females. This can be observed in sex hormone-immune interaction where androgens, such as testosterone, have shown immunosuppressive effects whilst estrogen is on the opposite side of the spectrum with immunoenhancing facilitation of mechanisms. In addition, the two sexes exhibit significant differences in metabolic regulation, with estrous cycles in females known to induce variability in traits and more pronounced metabolic disease phenotype exhibited by males. It is likely that these differences underlie both the development of metabolic and autoimmune diseases and the response to current treatment options. Sexual dimorphism in immunometabolism has emerged to become an area of intense research, aiming to uncover sex-biased effector molecules in the various metabolic tissues and immune cell types, identify sex-biased cell-type-specific functions of common effector molecules, and understand whether the sex differences in metabolic and immune functions influence each other during autoimmune pathogenesis. In this review, we will summarize recent findings that address these critical questions of sexual dimorphism in immunometabolism as well as their translational implications for the clinical management of autoimmune diseases.