Diverse Synthesis of C-Glycosides by Stereoselective Ni-Catalyzed Carboboration of Glycals.

C-Glycosides are important structures that are common to natural products and pharmaceutical agents. Established methods for their synthesis involve the reaction of an activated anomeric carbon. In this study, we report a conceptually new approach that involves the stereoselective Ni-catalyzed carboboration of glycals. In these reactions, not only is a C-C bond formed at the anomeric carbon, but a synthetically useful C-B bond is also installed. Upon C-B oxidation, differentially protected C-glycosides to be formed. In addition, stereospecific manipulation of the C-B bond leads to diverse C-glycosides. Finally, we report the application of this method in the synthesis of established C-glycosides, such as C-glycosyl amino acids, as well as a strategy to make all possible diastereomers at C1 and C2.

The importance of place-kicking in Women's International Rugby Union.

Despite the growing popularity of women's rugby, there is a lack of research understanding the contribution of place-kicking to match outcomes. This study aims to establish the characteristics and contribution of place-kicking to women's international Rugby Union and evaluate the performance of place-kickers while accounting for factors that contribute to kick difficulty. Data from 674 place-kicks across 80 matches were analysed. A binomial generalised linear mixed model (GLMM) was used to predict the probability of kick success. 60.5% of place-kicks were successful, and they contributed 23.9% of all points scored; conversions accounted for 16.8% and penalties 7.1%. Kick success percentages for conversions (56.9%) and penalties (78.3%) significantly differed (p < 0.01). Kick distance and angle were significant (p < 0.01) predictors of kick success and the GLMM had a prediction accuracy of 73.6%. The performance rankings of kickers changed when comparing observed and expected success, highlighting the need to consider contextual factors contributing to kick difficulty when evaluating performance. The GLMM results provide valuable insights for coaches and players to make informed decisions, for example, whether to attempt a place-kick when a penalty is awarded, by enabling predictions of place-kick success. This could enhance a team's chances of winning matches.

Single organ metastatic sites in non-small cell lung cancer: Patient characteristics, treatment patterns and outcomes from a large retrospective Canadian cohort.

BACKGROUND: There is a paucity of information about the characteristics, treatment patterns, and outcomes of non-small cell lung cancer (NSCLC) patients with single organ metastasis (SOM). METHODS: This retrospective cohort study includes all patients with a diagnosis of stage IV NSCLC diagnosed from 2014 to 2016 and treated at Princess Margaret Cancer Centre. We compared baseline characteristics and patterns of metastatic sites between patients with SOM versus multiple (M)OM. Additionally, we identified treatment modalities and outcomes for patients with SOM. Cox multivariable models (MVA) were utilized to evaluate differences in overall survival (OS) between the SOM and MOM cohorts. RESULTS: Of 893 pts analyzed, 457 (51 %) had SOM, while 436 (49 %) had MOM at initial diagnosis. Demographics were comparable between the two groups. Brain was the most common site of metastasis for SOM patients. When compared to the MOM group, the SOM group had lower percentages of liver and adrenal metastases. Amongst SOM patients, 54 % received single modality treatment, and 20 % did not receive any treatment for their SOM. In MVA, patients with liver (HR 2.4), bone (HR 1.8), and pleural (HR 1.7) metastasis as their SOM site had the worst outcomes, with median OS of 6.8 months, 12.1 months, and 13.0 months respectively. Patients with SOM had a significantly improved median OS compared to those with MOM (15.9 months vs. 10.6 months; HR 0.56, 95 % CI 0.47-0.66, p < 0.001). CONCLUSION: In NSCLC patients who presented with SOM, survival correlated with the initial organ involved and was better overall compared to patients with MOM. SOM NSCLC may benefit from specific management strategies and SOM patients could be considered as a specific subgroup for survival analyses in observational and non-randomized interventional studies. In clinical trials, SOM can be considered as a stratification factor in the future.

Designing and implementing an Advanced Nurse Practice in Critical Care programme from a university perspective within Northern Ireland.

The number of advanced practice roles in healthcare is increasing in response to several factors such as changes in medical education, economic pressures, workforce shortages and the increasing complexity of health needs of the population. The Advanced Critical Care Practitioner Curriculum, developed by the Faculty of Intensive Care Medicine in the UK (United Kingdom), enables the development and delivery of a structured education programme which can contribute to addressing these challenges. This article outlines how one university designed and implemented this programme, the first of its kind in Northern Ireland.

Nurse-led renal cell carcinoma clinic: a single center review.

BACKGROUND: In 2015 our centre introduced a nurse-led renal cell cancer follow-up protocol and clinic for patients who have undergone partial or radical nephrectomy for organ-confined kidney tumours. The main aims of this clinic were to improve healthcare efficiency and standardize follow-up processes. OBJECTIVES: The primary objective was to assess the effectiveness of a nurse-led renal cell cancer follow up clinic in regard to surveillance protocol compliance and the timely identification and appropriate management of recurrences. A secondary objective was to evaluate this locally developed follow up protocol against the current European Association of Urology (EAU) guidelines surveillance protocol. PATIENT AND METHODS: All patients who underwent a partial or radical nephrectomy between 2015 and 2021 at a single Western Australia institution for a primary renal malignancy were included. Data was collected from local clinical information systems and protocol adherence, recurrence characteristics and management were assessed. The current EAU guidelines were applied to the cohort to assess differences in risk-stratification and theoretical outcomes between the protocols. RESULTS: After a mean follow up period of 31.2 months (range 0-77 months), 75.5% (185/245) of patients had all follow up imaging and reviews within 1 month of the timeframe scheduled on the protocol. 17.1% (42/245) had a delay in their follow up of more than a month at some stage, 5.7% (14/245) did not attend for follow up but had documented attempts to facilitate their compliance, and 0.4% (1/245) were lost to follow up with no evidence of attempted contact. 15.5% (38/245) of patients had recurrence of malignancy detected during follow up and these were all discussed in a multi-disciplinary team (MDT) meeting. The recurrence rate was 2.5% (3/119) for low risk, 17.7% (14/79) for intermediate risk, and 44.7% (21/47) for high risk patients when they were re-stratified according to EAU risk categories. No recurrences were detected through ultrasound (USS) or chest x-ray (CXR) in this cohort and our protocol tended to place patients in higher risk-stratification groups as compared to current EAU guidelines. CONCLUSION: Nurse-led renal cell cancer follow up is a safe, reliable and effective clinical framework that has significant benefits in regard to resource utilization. USS and CXR are ineffective in detecting recurrence and Computerized tomography (CT) should be considered the imaging modality of choice for this purpose. The EAU surveillance protocol appears superior to our protocol, and we have therefore transitioned to the EAU guideline protocol going forward.

System-level recommendations for improved wellness for gynecologic oncologists: A Society of Gynecologic Oncology Review.

Burnout and its negative sequelae are a persistent problem in gynecologic oncology, threatening the health of our physician workforce. Individual-level interventions such as stress management training, physical activity, and sleep hygiene only partially address this widespread, systemic crisis rooted in the extended work hours and stressful situations associated with gynecologic oncology practice. There is an urgent need for systematic, institution-level changes to allow gynecologic oncologists to continue the crucial work of caring for people with gynecologic cancer. We present recommendations for institution-level changes which are grounded in the framework presented by the National Plan for Health Workforce Well-Being by the National Academy of Medicine. These are aimed at facilitating gynecologic oncologists' well-being and reduction of burnout. Recommendations include efforts to create a more positive and inclusive work environment, decrease administrative barriers, promote mental health, optimize electronic medical record use, and support a diverse workforce. Implementation and regular evaluation of these interventions, with specific attention to at-risk groups, is an important next step.

Synthesis of Borylated Carbocycles by [2 + 2]-Cycloadditions and Photo-Ene Reactions.

Saturated bicyclic compounds make up a valuable class of building blocks in the development of agrochemicals and pharmaceuticals. Here, we present the synthesis of borylated bicyclo[2.1.1]hexanes via crossed [2 + 2]-cycloaddition. Due to the presence of the C-B bond, a variety of structures can be easily prepared that are not accessible by other methods. Moreover, a rare photo-ene reaction is also disclosed, allowing for the diastereoselective synthesis of trisubstituted borylated cyclopentanes.

A National audit of the care of patients with acute kidney injury in England and Wales in 2019 and the association with patient outcomes.

BACKGROUND: Acute kidney injury (AKI) is a common complication of hospitalisations. This national audit assessed the care received by patients with AKI in hospital Trusts in England and Wales. METHODS: Twenty four hospital Trusts across England and Wales took part. Patients with AKI stage2/3 were identified using the UK Renal Registry AKI master patient index. Data was returned through a secure portal with linkage to hospital episode statistic mortality and hospitalisation data. Completion rates of AKI care standards and regional variations in care were established. RESULTS: 989 AKI episodes were included in the analyses. In-hospital 30-day mortality was 31-33.1% (AKI 2/3). Standard AKI interventions were completed in >80% of episodes. Significant inter-hospital variation remained in attainment of AKI care standards after adjustment for age and sex. Recording of urinalysis (41.9%) and timely imaging (37.2%) were low. Information on discharge summaries relating to medication changes/re-commencement and follow-up blood tests associated with reduced mortality. No quality indicators relating to clinical management associated with mortality. Better communication on discharge summaries associated with reduced mortality. CONCLUSIONS: Outcomes for patients with AKI in hospital remain poor. Regional variation in care exists. Work is needed to assess whether improving and standardising care improves patient outcomes.

Auditory Brainstem Implant Outcomes in Tumor and Nontumor Patients: A Systematic Review.

OBJECTIVE: To elucidate the differences in auditory performance between auditory brainstem implant (ABI) patients with tumor or nontumor etiologies. DATA SOURCES: PubMed, Embase, and Web of Science Core Collection from 1990 to 2021. REVIEW METHODS: We included published studies with 5 or more pediatric or adult ABI users. Auditory outcomes and side effects were analyzed with weighted means for closed-set, open-set speech, and categories of auditory performance (CAP) scores. Overall performance was compared using an Adult Pediatric Ranked Order Speech Perception (APROSPER) scale created for this study. RESULTS: Thirty-six studies were included and underwent full-text review. Data were extracted for 662 tumor and 267 nontumor patients. 83% were postlingually deafened and 17% were prelingually deafened. Studies that included tumor ABI patients had a weighted mean speech recognition of 39.2% (range: 19.6%-83.3%) for closed-set words, 23.4% (range: 17.2%-37.5%) for open-set words, 21.5% (range: 2.7%-48.4%) for open-set sentences, and 3.1 (range: 1.0-3.2) for CAP scores. Studies including nontumor ABI patients had a weighted mean speech recognition of 79.8% (range: 31.7%-84.4%) for closed-set words, 53.0% (range: 14.6%-72.5%) for open-set sentences, and 2.30 (range: 2.0-4.7) for CAP scores. Mean APROSPER results indicate better auditory performance among nontumor versus tumor patients (3.5 vs 3.0, P = .04). Differences in most common side effects were also observed between tumor and nontumor ABI patients. CONCLUSION: Auditory performance is similar for tumor and nontumor patients for standardized auditory test scores. However, the APROSPER scale demonstrates better ABI performance for nontumor compared to tumor patients.

Mercury bioaccumulation and Hepatozoon spp. infections in two syntopic watersnakes in South Carolina.

Mercury (Hg) is a ubiquitous environmental contaminant known to bioaccumulate in biota and biomagnify in food webs. Parasites occur in nearly every ecosystem and often interact in complex ways with other stressors that their hosts experience. Hepatozoon spp. are intraerythrocytic parasites common in snakes. The Florida green watersnake (Nerodia floridana) and the banded watersnake (Nerodia fasciata) occur syntopically in certain aquatic habitats in the Southeastern United States. The purpose of this study was to investigate relationships among total mercury (THg) concentrations, body size, species, habitat type and prevalence and parasitemia of Hepatozoon spp. infections in snakes. In the present study, we sampled N. floridana and N. fasciata from former nuclear cooling reservoirs and isolated wetlands of the Savannah River Site in South Carolina. We used snake tail clips to quantify THg and collected blood samples for hemoparasite counts. Our results indicate a significant, positive relationship between THg and snake body size in N. floridana and N. fasciata in both habitats. Average THg was significantly higher for N. fasciata compared to N. floridana in bays (0.22 ± 0.02 and 0.08 ± 0.006 mg/kg, respectively; p < 0.01), but not in reservoirs (0.17 ± 0.02 and 0.17 ± 0.03 mg/kg, respectively; p = 0.29). Sex did not appear to be related to THg concentration or Hepatozoon spp. infections in either species. We found no association between Hg and Hepatozoon spp. prevalence or parasitemia; however, our results suggest that species and habitat type play a role in susceptibility to Hepatozoon spp. infection.

Advance care planning for patients with end-stage kidney disease on dialysis: narrative review of the current evidence, and future considerations.

Patients with end-stage kidney disease (ESKD) have a high symptom-burden and high rates of morbidity and mortality. Despite this, evidence has shown that this patient group does not have timely discussions to plan for deterioration and death, and at the end of life there are unmet palliative care needs. Advance care planning is a process that can help patients share their personal values and preferences for their future care and prepare for declining health. Earlier, more integrated and holistic advance care planning has the potential to improve access to care services, communication, and preparedness for future decision-making and changing circumstances. However, there are many barriers to successful implementation of advance care planning in this population. In this narrative review we discuss the current evidence for advance care planning in patients on dialysis, the data around the barriers to advance care planning implementation, and interventions that have been trialled. The review explores whether the concepts and approaches to advance care planning in this population need to be updated to encompass current and future care. It suggests that a shift from a problem-orientated approach to a goal-orientated approach may lead to better engagement, with more patient-centred and satisfying outcomes.

COVID-19 pandemic impact on adolescent mental health: a reassessment accounting for development.

Current prospective reports suggest a pandemic-related increase in adolescent mental health problems. We examine whether age-related change over 11-14 years accounts for this increase. Mothers and adolescents in a UK-based birth cohort (Wirral Child Health and Development Study; WCHADS; N = 737) reported on adolescent depression and behavioural problems pre-pandemic (December 2019-March 2020), mid-pandemic (June 2020-March 2021) and late pandemic (July 2021-March 2022). Analysis used repeated measures models for over-dispersed Poisson counts with an adolescent-specific intercept with age as a time-varying covariate. Maturational curves for girls, but not for boys, showed a significant increase in self-reported depression symptoms over ages 11-14 years. Behavioural problems decreased for both. After adjusting for age-related change, girls' depression increased by only 13% at mid-pandemic and returned to near pre-pandemic level at late pandemic (mid versus late - 12%), whereas boys' depression increased by 31% and remained elevated (mid versus late 1%). Age-adjusted behavioural problems increased for both (girls 40%, boys 41%) and worsened from mid- to late pandemic (girls 33%, boys 18%). Initial reports of a pandemic-related increase in depression in young adolescent girls could be explained by a natural maturational rise. In contrast, maturational decreases in boys' depression and both boys' and girls' behavioural problems may mask an effect of the pandemic.

Photochemical Reduction of Quinolines with γ-Terpinene.

The saturation of aromatic scaffolds is valuable for the synthesis of complex rings. Herein, we demonstrate a process for photochemical dearomative reduction of quinolines. The process involves capture of a quinoline excited state with γ-terpinene. Importantly, the reaction is chemoselective as other easily reduced functionalities such as halogens or alkenes do not undergo reduction. The mechanism of the reaction has also been investigated. Finally, the generality of the approach towards other substrates is demonstrated.

Nutritional composition of ultra-processed plant-based foods in the out-of-home environment: a multi-country survey with plant-based burgers.

Ultra-processed plant-based foods, such as plant-based burgers, have gained in popularity. Particularly in the out-of-home (OOH) environment, evidence regarding their nutritional profile and environmental sustainability is still evolving. Plant-based burgers available at selected OOH sites were randomly sampled in Amsterdam, Copenhagen, Lisbon and London. Plant-based burgers (patty, bread and condiment) (n 41) were lab analysed for their energy, macronutrients, amino acids and minerals content per 100 g and serving and were compared with reference values. For the plant-based burgers, the median values per 100 g were 234 kcal, 20·8 g carbohydrates, 3·5 g dietary fibre and 12·0 g fat, including 0·08 g TFS and 2·2 g SFA. Protein content was 8·9 g/100 g, with low protein quality according to amino acid composition. Median Na content was 389 mg/100 g, equivalent to 1 g salt. Compared with references, the median serving provided 31% of energy intake based on a 2000 kcal per day and contributed to carbohydrates (17-28%), dietary fibre (42%), protein (40%), total fat (48%), SFA (26%) and Na (54%). One serving provided 15-23% of the reference values for Ca, K and Mg, while higher contributions were found for Zn, Mn, P and Fe (30-67%). The ultra-processed plant-based burgers provide protein, dietary fibre and essential minerals and contain relatively high levels of energy, Na and total fats. The amino acid composition indicated low protein quality. The multifaceted nutritional profile of plant-based burgers highlights the need for manufacturers to implement improvements to better support healthy dietary habits, including reducing energy, Na and total fats.

Factors Predicting Apparent Ophidiomycosis in Wild Brown Watersnakes (Nerodia taxispilota).

Ophidiomycosis, also known as snake fungal disease, is caused by Ophidiomyces ophidiicola and is a threat to snake conservation worldwide. Ophidiomycosis has been reported throughout much of the eastern US, and outbreaks have been associated with local population declines of already strained populations. Previous studies report significant variability in ophidiomycosis among species sampled, with higher prevalence typically observed in Nerodia spp. Although ophidiomycosis can lead to morbidity and mortality in affected individuals, little is known about disease dynamics in free-ranging populations. Herein, we examine how individual-specific factors (e.g., life stage [immature, mature], contaminant status, sex, hemograms) may be associated with ophidiomycosis status in the brown watersnake (Nerodia taxispilota). During 2018-19, we sampled 97 N. taxispilota from five locations along the Savannah River in South Carolina and Georgia, US. Ophidiomyces ophidiicola DNA was detected in 66 snakes for a prevalence of 68% (95% confidence interval, 59-77). Mature snakes had a significantly higher risk of apparent ophidiomycosis (skin lesions present and quantitative PCR [qPCR], positive) relative to immature snakes. Snakes classified as having possible (skin lesions present, but qPCR negative) or apparent ophidiomycosis exhibited a relative azurophilia and heterophilia compared with individuals classified as negative (P≤0.037). Nerodia taxispilota in this region appear to have a high prevalence of apparent ophidiomycosis (22%; 95% CI, 14-31), similar to previous reports from the southeastern US. Additional epidemiologic investigations are warranted to further elucidate other individual-specific and environmental factors that may dictate disease risk and outcomes in affected populations.

Ni-Catalyzed 1,1- and 1,3-Aminoboration of Unactivated Alkenes.

Alkene borylfunctionalization reactions have emerged as useful methods for chemical synthesis. While much progress has been made on 1,2-borylamination reactions, the related 1,1- and 1,3-borylaminations have not been reported. Herein, a Ni-catalyzed 1,1-borylamination of 1,1-disubstituted and monosubstituted alkenes and a 1,3-borylamination of cyclic alkenes are presented. Key to development of these reactions was the identification of an alkyllithium activator in combination with Mg salts. The utility of the products and the mechanistic details are discussed.

Pediatric cartilaginous lateral femoral condyle Hoffa fracture: a case report and review of the literature.

INTRODUCTION: Hoffa fractures are challenging coronally-oriented articular injuries of the femoral condyle. These fractures are rare in adults and extremely rare in the skeletally immature, with few cases reported in literature. To prevent mal- or non-union, Hoffa fractures require prompt surgical stabilisation with anatomic reduction and internal fixation. CASE REPORT: We discuss the case of a lateral distal femoral condyle cartilaginous Hoffa fracture in a ten-year-old male patient. The patient presented after a football non-contact "twist and pop" injury with radiographic imaging described as an osteochondritis dissecans lesion. An MRI was obtained which demonstrated a lateral distal femoral condyle osteochondral fracture. An operative plan was formulated to perform arthroscopic reduction and bio-compression screw fixation to minimize damage to the physis and surrounding tissues. Hyperflexion of the knee allowed for anatomic fracture reduction with the placement of 2 bio-compression screws serving as maintenance of fixation. The patient did well postoperatively and returned to full activity after 6 months. CONCLUSION: Hoffa fractures in the pediatric population are rare and can occur not only through bone but also through the thick chondral layer in younger patients. These are extremely difficult to diagnose through X-Ray alone. The prompt use of MRI imaging allows for operative fixation in a timely fashion, while an arthroscopic-only approach allows for minimal tissue damage. With an appropriate fracture type, hyper-flexion reduces and stabilizes the fracture, permitting the placement of minimally invasive bio-compression fixation.

Experiences of UK and Irish family carers of people with profound and multiple intellectual disabilities during the COVID-19 pandemic.

BACKGROUND: People with profound and multiple intellectual disabilities (PMID) have high and intensive support needs that ordinarily place significant strain on family carers. This was further heightened by the removal of many external supports during the COVID-19 pandemic. We sought to explore the experiences of family carers of people with PMID during the COVID-19 pandemic and understand what the longer-term impact might be on their lives. METHODS: Focus group interviews (n = 32) were conducted with family carers (n = 126) from the four countries of the UK and the Republic of Ireland. Participants were asked questions relating to their experiences of the COVID-19 pandemic, coping strategies, and challenges faced. All focus groups were conducted using the online platform, Zoom. These were audio recorded, transcribed verbatim and analysed employing inductive thematic analysis. FINDINGS: Three main themes were generated from the data including (1.0) COVID-19 as a double-edged sword (2.0), The struggle for support (3.0), Constant nature of caring. These included 11 subthemes. (1.1) 'COVID-19 as a catalyst for change', (1.2) 'Challenges during COVID-19: dealing with change', (1.3) 'Challenges during COVID-19: fear of COVID-19', (1.4); 'The online environment: the new normal' (2.1) 'Invisibility of male carers', (2.2) 'Carers supporting carers', (2.3) 'The only service you get is lip service: non-existent services', (2.4); 'Knowing your rights' (3.1) 'Emotional response to the caring role: Feeling devalued', (3.2) 'Emotional response to the caring role: Desperation of caring', (3.3) 'Multiple demands of the caring role.' CONCLUSIONS: The COVID-19 pandemic presented immense challenges to family carers of people with PMID but also provided some opportunities. Families had already struggled to receive many of the supports and services to which they were entitled to only to have these removed at the onset of the pandemic. The experiences of male carers have been largely absent from the literature with this research showing they want to be included in decision making and require tailored support services. Service providers should see the end of the COVID-19 pandemic as providing opportunity to re-examine current provision and design services with family carers. As the direct threat from COVID-19 diminishes and the experiences of those who lived through this period come to the fore, there is a need to re-examine current models and provision of support to family carers to better meet their needs.

Synthesis of 2-Azanorbornanes via Strain-Release Formal Cycloadditions Initiated by Energy Transfer.

Rigid bicycles are becoming more popular in the pharmaceutical industry because they allow for expansion to new and unique chemical spaces. This work describes a new strategy to construct 2-azanorbornanes, which can act as rigid piperidine/pyrrolidine scaffolds with well-defined exit vectors. To achieve the synthesis of 2-azanorbornanes, new strain-release reagent, azahousane, is introduced along with its photosensitized strain-release formal cycloaddition with alkenes. Furthermore, new reactivity between a housane and an imine is disclosed. Both strategies lead to various substituted 2-azanorbornanes with good selectivities.

Photosensitized [2 + 2]-Cycloadditions of Dioxaborole: Reactivity Enabled by Boron Ring Constraint Strategy.

A strategy to achieve photosensitized [2 + 2] cycloadditions by means of temporary ring constraint is reported. Specifically, a dioxaborole is prepared that undergoes [2 + 2] cycloadditions with a wide variety of alkenes. This strategy overcomes some challenges with the cycloaddition of acyclic substrates. The products can be easily transformed into cyclobutyl diols or 1,4-dicarbonyl compounds; the latter represents a formal alkene vicinal diacylation. The synthetic utility of this method is shown in the synthesis of valuable heterocycles and biatriosporin D.