Forecasting species' responses to climate change using space-for-time substitution.

To anticipate species' responses to climate change, ecologists have largely relied on the space-for-time-substitution (SFTS) approach. However, the hypothesis and its underlying assumptions have been poorly tested. Here, we detail how the efficacy of using the SFTS approach to predict future locations will depend on species' traits, the ecological context, and whether the species is declining or introduced. We argue that the SFTS approach will be least predictive in the contexts where we most need it to be: forecasting the expansion of the range of introduced species and the recovery of threatened species. We highlight how evaluating the underlying assumptions, along with improved methods, will rapidly advance our understanding of the applicability of the SFTS approach, particularly in the context of modelling the distribution of species.

Characterization of the mode of action of eCry1Gb.1Ig, a fall armyworm (Spodoptera frugiperda) active protein, with a novel site of action.

Insect pests cause immense agronomic losses worldwide. One of the most destructive of major crops is the Fall Armyworm (Spodoptera frugiperda, FAW). The ability to migrate long distances, a prodigious appetite, and a demonstrated ability to develop resistance to insecticides, make it a difficult target to control. Insecticidal proteins, for example those produced by the bacterium Bacillus thuringiensis, are among the safest and most effective insect control agents. Genetically modified (GM) crops expressing such proteins are a key part of a successful integrated pest management (IPM) program for FAW. However, due to the development of populations resistant to commercialized GM products, new GM traits are desperately needed. Herein, we describe a further characterization of the newly engineered trait protein eCry1Gb.1Ig. Similar to other well characterized Cry proteins, eCry1Gb.1Ig is shown to bind FAW midgut cells and induce cell-death. Binding competition assays using trait proteins from other FAW-active events show a lack of competition when binding FAW brush border membrane vesicles (BBMVs) and when utilizing non-pore-forming versions as competitors in in vivo bioassays. Similarly, insect cell lines expressing SfABCC2 and SfABCC3 (well characterized receptors of existing commercial Cry proteins) are insensitive to eCry1Gb.1Ig. These findings are consistent with results from our previous work showing that eCry1Gb.1Ig is effective in controlling insects with resistance to existing traits. This underscores the value of eCry1Gb.1Ig as a new GM trait protein with a unique site-of-action and its potential positive impact to global food production.

Folate and vitamin B12 status and predicted neural tube defects risk among nonpregnant women of reproductive age from the Malawi National Micronutrient Survey, 2015-2016.

BACKGROUND: Maternal folate and vitamin B12 deficiency can lead to serious adverse pregnancy outcomes. There are no nationally representative estimates on folate and vitamin B12 status among women of reproductive age (WRA) in Malawi. OBJECTIVE: We assessed folate and vitamin B12 status among nonpregnant WRA in Malawi and predicted the risk of folate-sensitive neural tube defects (NTDs) were they to become pregnant. METHODS: Using data from the cross-sectional, nationally representative 2015-2016 Malawi Micronutrient Survey, we calculated the proportion of folate and vitamin B12 deficiency and insufficiency by demographic characteristics among 778 nonpregnant WRA (15-49 years). We predicted NTD prevalence using red blood cell (RBC) folate distributions and a published Bayesian model of the association between RBC folate and NTD risk. Analyses accounted for complex survey design. RESULTS: Among WRA, 8.5% (95% CI: 6.2, 11.6) and 13.3% (10.0, 17.4) had serum (<7 nmol/L) and RBC folate (<305 nmol/L) deficiency, respectively. The proportion of vitamin B12 deficiency (<148 pmol/L) and insufficiency (≤221 pmol/L) was 11.8% (8.6, 16.0) and 40.6% (34.1, 47.4), respectively. RBC folate insufficiency (<748 nmol/L, defined as the concentration associated with the threshold for elevated NTD risk: >8 cases per 10,000 births) was widespread: 81.4% (75.0, 86.4). The predicted NTD risk nationally was 24.7 cases per 10,000 live births. RBC folate insufficiency and higher predicted NTD risk were more common among WRA living in urban areas or with higher education. CONCLUSIONS: These findings highlight the importance of nutritional and NTD surveillance in Malawi and the opportunity for improving folate and vitamin B12 nutrition among Malawian WRA.

Update on the impact of voluntary folic acid fortification of corn masa flour on red blood cell folate concentrations-National Health and Nutrition Examination Survey, 2011-March 2020.

BACKGROUND: Folic acid is a micronutrient that is effective at preventing neural tube defects (NTDs). In 2016, the FDA authorized the voluntary fortification of corn masa flour (CMF) with folic acid to reduce disparities in NTDs among infants of women who do not regularly consume other fortified cereal grains, in particular Hispanic women of reproductive age (WRA). METHODS: We analyzed data from the National Health and Nutrition Examination Survey (NHANES) from 2011 to March 2020 assessing the impact of voluntary fortification of CMF on the folate status of Hispanic WRA. We analyzed folic acid usual intake and red blood cell (RBC) folate concentrations among non-pregnant, non-lactating Hispanic WRA, comparing pre-fortification (2011-2016) to post-fortification (2017-March 2020) data. RBC folate concentrations were used to create model-based estimation of NTD rates. RESULTS: The proportion of Hispanic WRA with folic acid usual intakes <400 µg/d did not change (2011-2016: 86.1% [95% Confidence Interval, CI: 83.7-88.5]; 2017-March 2020: 87.8% [95% CI: 84.8-90.7]; p = .38) nor did the proportion of Hispanic WRA with RBC folate below optimal concentrations (<748 nmol/L, 2011-2016: 16.0% [95% CI: 13.7-18.2]; 2017-March 2020: 18.1% [95% CI: 12.1-24.0]; p = 0.49). Model-based estimates of NTD rates suggest further improvements in the folate status of Hispanic WRA might prevent an additional 157 (95% Uncertainty Interval: 0, 288) NTDs/year. CONCLUSIONS: Voluntary fortification of CMF with folic acid has yet to have a significant impact on the folate status of WRA. Continued monitoring and further research into factors such as fortified product availability, community knowledge, and awareness of folic acid benefits would inform and improve future public health interventions.

Vitamin B12 supplementation during pregnancy for maternal and child health outcomes.

BACKGROUND: Vitamin B12 deficiency is a major public health problem worldwide, with the highest burden in elderly people, pregnant women, and young children. Due to its role in DNA synthesis and methylation, folate metabolism, and erythropoiesis, vitamin B12 supplementation during pregnancy may confer longer-term benefits to maternal and child health outcomes. OBJECTIVES: To evaluate the benefits and harms of oral vitamin B12 supplementation during pregnancy on maternal and child health outcomes. SEARCH METHODS: We searched the Cochrane Pregnancy and Childbirth's Trials Register, ClinicalTrials.gov, the World Health Organization International Clinical Trials Registry Platform (ICTRP) on 2 June 2023, and reference lists of retrieved studies. SELECTION CRITERIA: Randomised controlled trials (RCTs), quasi-RCTs, or cluster-RCTs evaluating the effects of oral vitamin B12 supplementation compared to placebo or no vitamin B12 supplementation during pregnancy. DATA COLLECTION AND ANALYSIS: We used standard Cochrane methods. Four review authors independently assessed trial eligibility. Two review authors independently extracted data from included studies and conducted checks for accuracy. Three review authors independently assessed the risk of bias of the included studies using the Cochrane RoB 1 tool. We used GRADE to evaluate the certainty of evidence for primary outcomes. MAIN RESULTS: The review included five trials with 984 pregnant women. All trials were conducted in low- and middle-income countries, including India, Bangladesh, South Africa, and Croatia. At enrolment, 26% to 51% of pregnant women had vitamin B12 deficiency (less than 150 pmol/L), and the prevalence of anaemia (haemoglobin less than 11.0 g/dL) ranged from 30% to 46%. The dosage of vitamin B12 supplementation varied from 5 µg/day to 250 µg/day, with administration beginning at 8 to 28 weeks' gestation through to delivery or three months' postpartum, and the duration of supplementation ranged from 8 to 16 weeks to 32 to 38 weeks. Three trials, involving 609 pregnant women, contributed data for meta-analyses of the effects of vitamin B12 supplementation compared to placebo or no vitamin B12 supplementation. Maternal anaemia: there may be little to no difference for maternal anaemia by intervention group, but the evidence is very uncertain (70.9% versus 65.0%; risk ratio (RR) 1.08, 95% confidence interval (CI) 0.93 to 1.26; 2 trials, 284 women; very low-certainty evidence). Maternal vitamin B12 status: vitamin B12 supplementation during pregnancy may reduce the risk of maternal vitamin B12 deficiency compared to placebo or no vitamin B12 supplementation, but the evidence is very uncertain (25.9% versus 67.9%; RR 0.38, 95% CI 0.28 to 0.51; 2 trials, 272 women; very low-certainty evidence). Women who received vitamin B12 supplements during pregnancy may have higher total vitamin B12 concentrations compared to placebo or no vitamin B12 supplementation (mean difference (MD) 60.89 pmol/L, 95% CI 40.86 to 80.92; 3 trials, 412 women). However, there was substantial heterogeneity (I2 = 85%). Adverse pregnancy outcomes: the evidence is uncertain about the effect on adverse pregnancy outcomes, including preterm birth (RR 0.97, 95% CI 0.55 to 1.74; 2 trials, 340 women; low-certainty evidence), and low birthweight (RR 1.50, 95% CI 0.93 to 2.43; 2 trials, 344 women; low-certainty evidence). Two trials reported data on spontaneous abortion (or miscarriage); however, the trials did not report quantitative data for meta-analysis and there was no clear definition of spontaneous abortion in the study reports. No trials evaluated the effects of vitamin B12 supplementation during pregnancy on neural tube defects. Infant vitamin B12 status: children born to women who received vitamin B12 supplementation had higher total vitamin B12 concentrations compared to placebo or no vitamin B12 supplementation (MD 71.89 pmol/L, 95% CI 20.23 to 123.54; 2 trials, 144 children). Child cognitive outcomes: three ancillary analyses of one trial reported child cognitive outcomes; however, data were not reported in a format that could be included in quantitative meta-analyses. In one study, maternal vitamin B12 supplementation did not improve neurodevelopment status (e.g. cognitive, language (receptive and expressive), motor (fine and gross), social-emotional, or adaptive (conceptual, social, practical) domains) in children compared to placebo (9 months, Bayley Scales of Infant and Toddler Development Third Edition (BSID-III); 1 trial; low-certainty evidence) or neurophysiological outcomes (72 months, event-related potential measures; 1 trial; low-certainty evidence), though children born to women who received vitamin B12 supplementation had improved expressive language domain compared to placebo (30 months, BSID-III; 1 trial; low-certainty evidence). AUTHORS' CONCLUSIONS: Oral vitamin B12 supplementation during pregnancy may reduce the risk of maternal vitamin B12 deficiency and may improve maternal vitamin B12 concentrations during pregnancy or postpartum compared to placebo or no vitamin B12 supplementation, but the evidence is very uncertain. The effects of vitamin B12 supplementation on other primary outcomes assessed in this review were not reported, or were not reported in a format for inclusion in quantitative analyses. Vitamin B12 supplementation during pregnancy may improve maternal and infant vitamin B12 status, but the potential impact on longer-term clinical and functional maternal and child health outcomes has not yet been established.

Diagnostic Workup and Therapeutic Intervention of Hiatal Hernias Discovered as Incidental Findings on Computed Tomography.

BACKGROUND: Computed tomography imaging routinely detects incidental findings; most research focuses on malignant findings. However, benign diseases such as hiatal hernia also require identification and follow-up. Natural language algorithms can help identify these non-malignant findings. METHODS: Imaging of adult trauma patients from 2010 to 2020 who underwent CT chest/abdomen/pelvis was evaluated using an open-source natural language processor to query for hiatal hernias. Patients who underwent subsequent imaging, endoscopy, fluoroscopy, or operation were retrospectively reviewed. RESULTS: 1087(10.6%) of 10 299 patients had incidental hiatal hernias: 812 small (74.7%) and 275 moderate/large (25.3%). 224 (20.7%) had subsequent imaging or endoscopic evaluation. Compared to those with small hernias, patients with moderate/large hernias were older (66.3 ± 19.4 vs 79.6 ± 12.6 years, P < .001) and predominantly female (403[49.6%] vs 199[72.4%], P < .001). Moderate/large hernias were not more likely to grow (small vs moderate/large: 13[7.6%] vs 8[15.1%], P = .102). Patients with moderate/large hernias were more likely to have an intervention or referral (small vs moderate/large: 6[3.5%] vs 7[13.2%], P = .008). No patients underwent elective or emergent hernia repair. Three patients had surgical referral; however, only one was seen by a surgeon. One patient death was associated with a large hiatal hernia. CONCLUSIONS: We demonstrate a novel utilization of natural language processing to identify patients with incidental hiatal hernia in a large population, and found a 10.6% incidence with only 1.2%. (13/1087) of these receiving a referral for follow-up. While most incidental hiatal hernias are small, moderate/large and symptomatic hernias have high risk of loss-to-follow-up and need referral pipelines to improve patient outcomes.

Effect of a 2-week interruption in methotrexate treatment on COVID-19 vaccine response in people with immune-mediated inflammatory diseases (VROOM study): a randomised, open label, superiority trial.

BACKGROUND: Methotrexate is the first-line treatment for immune-mediated inflammatory diseases and reduces vaccine-induced immunity. We evaluated if a 2-week interruption of methotrexate treatment immediately after COVID-19 booster vaccination improved antibody response against the S1 receptor binding domain (S1-RBD) of the SARS-CoV-2 spike protein and live SARS-CoV-2 neutralisation compared with uninterrupted treatment in patients with immune-mediated inflammatory diseases. METHOD: We did a multicentre, open-label, parallel-group, randomised, superiority trial in secondary-care rheumatology and dermatology clinics in 26 hospitals in the UK. Adults (aged ≥18 years) with immune-mediated inflammatory diseases taking methotrexate (≤25 mg per week) for at least 3 months, who had received two primary vaccine doses from the UK COVID-19 vaccination programme were eligible. Participants were randomly assigned (1:1) using a centralised validated computer program, to temporarily suspend methotrexate treatment for 2 weeks immediately after COVID-19 booster vaccination or continue treatment as usual. The primary outcome was S1-RBD antibody titres 4 weeks after COVID-19 booster vaccination and was assessed masked to group assignment. All randomly assigned patients were included in primary and safety analyses. This trial is registered with ISRCTN, ISRCTN11442263; following a pre-planned interim analysis, recruitment was stopped early. FINDING: Between Sept 30, 2021, and March 7, 2022, we screened 685 individuals, of whom 383 were randomly assigned: to either suspend methotrexate (n=191; mean age 58·8 years [SD 12·5], 118 [62%] women and 73 [38%] men) or to continue methotrexate (n=192; mean age 59·3 years [11·9], 117 [61%] women and 75 [39%] men). At 4 weeks, the geometric mean S1-RBD antibody titre was 25 413 U/mL (95% CI 22 227-29 056) in the suspend methotrexate group and 12 326 U/mL (10 538-14 418) in the continue methotrexate group with a geometric mean ratio (GMR) of 2·08 (95% CI 1·59-2·70; p<0·0001). No intervention-related serious adverse events occurred. INTERPRETATION: 2-week interruption of methotrexate treatment in people with immune-mediated inflammatory diseases enhanced antibody responses after COVID-19 booster vaccination that were sustained at 12 weeks and 26 weeks. There was a temporary increase in inflammatory disease flares, mostly self-managed. The choice to suspend methotrexate should be individualised based on disease status and vulnerability to severe outcomes from COVID-19. FUNDING: National Institute for Health and Care Research.

Advance care planning for patients undergoing gastrostomy tube procedures; prevalence, outcomes, and disparities.

BACKGROUND: Advanced care planning (ACP) is the process of establishing goals for end-of-life care. We aimed to examine ACP's prevalence, associated factors, and impact in a cohort of patients undergoing gastrostomy tube procedures. METHODS: Adult patients who underwent gastrostomy tube placement from 2016 to 2021 â€‹at a tertiary center were identified. Variables evaluated included age, sex, race, comorbidities, and median income of patient home zip code. Primary outcomes included the presence of ACP, length of stay (LOS), and 90-day mortality. Analysis was performed using independent T tests, Mann Whitney U-tests, and Chi Square analysis. ACP, LOS, and 90-day mortality were analyzed with multivariate analysis. RESULTS: 877 patients underwent gastrostomy tube placement and 10.6 â€‹% had ACP. Black race was an isolated factor negatively associated with ACP (OR 0.423, p â€‹= â€‹0.013). There was no difference in the proportion of patients with or without ACP who died within 90 days of the procedure (17 â€‹% vs. 15 â€‹%, p â€‹= â€‹0.836). Average LOS was 6 days shorter for patients with ACP (p â€‹< â€‹0.001). CONCLUSION: This study highlights the significant underutilization and racial disparity in ACP, and found that ACP does not negatively impact outcomes or perioperative mortality for patients undergoing gastrostomy tube placement.

Working with roubles and failures in conversation between humans and robots: workshop report.

This paper summarizes the structure and findings from the first Workshop on Troubles and Failures in Conversations between Humans and Robots. The workshop was organized to bring together a small, interdisciplinary group of researchers working on miscommunication from two complementary perspectives. One group of technology-oriented researchers was made up of roboticists, Human-Robot Interaction (HRI) researchers and dialogue system experts. The second group involved experts from conversation analysis, cognitive science, and linguistics. Uniting both groups of researchers is the belief that communication failures between humans and machines need to be taken seriously and that a systematic analysis of such failures may open fruitful avenues in research beyond current practices to improve such systems, including both speech-centric and multimodal interfaces. This workshop represents a starting point for this endeavour. The aim of the workshop was threefold: Firstly, to establish an interdisciplinary network of researchers that share a common interest in investigating communicative failures with a particular view towards robotic speech interfaces; secondly, to gain a partial overview of the "failure landscape" as experienced by roboticists and HRI researchers; and thirdly, to determine the potential for creating a robotic benchmark scenario for testing future speech interfaces with respect to the identified failures. The present article summarizes both the "failure landscape" surveyed during the workshop as well as the outcomes of the attempt to define a benchmark scenario.

Biological sex does not influence the peak cardiac output response to twelve weeks of sprint interval training.

Sprint interval training (SIT) increases peak oxygen uptake (V̇O2peak) but the mechanistic basis is unclear. We have reported that 12 wk of SIT increased V̇O2peak and peak cardiac output (Q̇peak) and the changes in these variables were correlated. An exploratory analysis suggested that Q̇peak increased in males but not females. The present study incorporated best practices to examine the potential influence of biological sex on the Q̇peak response to SIT. Male and female participants (n = 10 each; 21 ± 4 y) performed 33 ± 2 sessions of SIT over 12 wk. Each 10-min session involved 3 × 20-s 'all-out' sprints on an ergometer. V̇O2peak increased after SIT (3.16 ± 1.0 vs. 2.89 ± 1.0 L/min, η2p = 0.53, p < 0.001) with no sex × time interaction (p = 0.61). Q̇peak was unchanged after training (15.2 ± 3.3 vs. 15.1 ± 3.0 L/min, p = 0.85), in contrast to our previous study. The peak estimated arteriovenous oxygen difference increased after training (204 ± 30 vs. 187 ± 36 ml/L, p = 0.006). There was no effect of training or sex on measures of endothelial function. We conclude that 12 wk of SIT increases V̇O2peak but the mechanistic basis remains unclear. The capacity of inert gas rebreathing to assess changes in Q̇peak may be limited and invasive studies that use more direct measures are needed.

Considering hormones as sex- and gender-related factors in biomedical research: Challenging false dichotomies and embracing complexity.

The inclusion of sex and gender considerations in biomedicine has been increasing in light of calls from research and funding agencies, governmental bodies, and advocacy groups to direct research attention to these issues. Although the inclusion of both female and male participants is often an important element, overreliance on a female-male binary tends to oversimplify the interactions between sex- and gender-related factors and health, and runs a risk of being influenced by cultural stereotypes about sex and gender. When biomedical researchers are examining how hormones associated with gender and sex may influence pathways of interest, it is of crucial importance to approach this work with a critical lens on the rhetoric used, and in ways that acknowledge the complexity of hormone physiology. Here, we document the ways in which discourses around sex, gender and hormones shape our scientific thinking and practice in biomedical research, and review how the existing scientific knowledge about hormones reflects a complex and dynamic reality that is often not reflected outside of specialist niches of hormone biology. Where biomedical scientists take up sex- and gender-associated hormones as a way of addressing sex and gender considerations, it is valuable for us to bring a critical lens to the rhetoric and discourses used, to employ a sex contextualist approach in designing experimentation, and be rigorous and reflexive about the approaches used in analysis and interpretation of data. These strategies will allow us to design experimentation that goes beyond binaries, and grapples more directly with the material intricacies of sex, gender, and hormones.

Strengthening capacity of health workers to diagnose birth defects in Ugandan hospitals from 2015 to 2021.

BACKGROUND: Limited diagnostic capabilities, resources and health worker skills have deterred the advancement of birth defects surveillance systems in most low- and middle-income countries (LMICs). Empowering health workers to identify and diagnose major external birth defects (BDs) is crucial to establishing effective hospital-based BD surveillance. Makerere University-Johns Hopkins University (MU-JHU) Research Collaboration BD Surveillance System consists of three diagnostic levels: (1) surveillance midwives, (2) MU-JHU clinical team, and (3) U.S. Centers for Disease Control and Prevention (CDC) birth defects subject matter experts (SMEs) who provide confirmatory diagnosis. The diagnostic concordance of major external BDs by surveillance midwives or MU-JHU clinical team with CDC birth defects SMEs were estimated. METHODS: Study staff went through a series of trainings, including birth defects identification and confirmation, before surveillance activities were implemented. To assess the diagnostic concordance, we analyzed surveillance data from 2015 to 2021 for major external BDs: anencephaly, iniencephaly, encephalocele, spina bifida, craniorachischisis, microcephaly, anophthalmia/microphthalmia, anotia/microtia, cleft palate alone, cleft lip alone, cleft lip with cleft palate, imperforate anus, hypospadias, talipes equinovarus, limb reduction, gastroschisis, and omphalocele. Positive predictive value (PPV) as the proportion of BDs diagnosed by surveillance midwives or MU-JHU clinical team that were confirmed by CDC birth defects SMEs was computed. PPVs between 2015 and 2018 and 2019-2021 were compared to assess the accuracy of case diagnosis over time. RESULTS: Of the 204,332 infants examined during 2015-2021, 870 infants had a BD. Among the 1,245 BDs identified, 1,232 (99.0%) were confirmed by CDC birth defects SMEs. For surveillance midwives, PPV for 7 of 17 BDs was > 80%. For the MU-JHU clinical team, PPV for 13 of 17 BDs was > 80%. Among surveillance midwives, PPV improved significantly from 2015 to 2018 to 2019-2021, for microcephaly (+ 50.0%), cleft lip with cleft palate (+ 17.0%), imperforate anus (+ 30.0%), and talipes equinovarus (+ 10.8%). Improvements in PPV were also observed among MU-JHU clinical team; however, none were significant. CONCLUSION: The diagnostic accuracy of the midwives and clinical team increased, highlighting that BD surveillance, by front-line health care workers (midwives) in LMICs is possible when midwives receive comprehensive training, technical support, funding and continuous professional development.

Cardiovascular Disease Risk Estimation for Transgender and Gender-Diverse Patients: Cross-Sectional Analysis of Baseline Data From the LITE Plus Cohort Study.

Introduction: Approximately 2% of the U.S. population identifies as transgender, and transgender people experience disproportionate rates of cardiovascular disease mortality. However, widely used cardiovascular disease risk estimators have not been validated in this population. This study sought to determine the impact on statin therapy recommendations using 3 different approaches to operationalizing sex in the American Health Association/American College of Cardiology Pooled Cohort Equation Risk Estimator. Methods: This is a cross-sectional analysis of baseline clinical data from LITE Plus, a prospective cohort study of Black and/or Latina transgender women with HIV. Data were collected from October 2020 to June 2022 and used to calculate Pooled Cohort Equation scores. Results: The 102 participants had a mean age of 43 years. A total of 88% were Black, and 18% were Latina. A total of 79% were taking gender-affirming hormones. The average Pooled Cohort Equation risk score was 6% when sex assigned at birth was used and statins would be recommended for the 31% with Pooled Cohort Equation >7.5%. The average risk score was 4%, and 18% met the criteria for statin initiation when current gender was used; the mean risk score was 5%, and 22% met the criteria for statin initiation when current hormone therapy was used. Conclusions: Average Pooled Cohort Equation risk scores vary substantially depending on the approach to operationalizing the sex variable, suggesting that widely used cardiovascular risk estimators may be unreliable predictors of cardiovascular disease risk in transgender populations. Collection of sex, gender, and hormone use in longitudinal studies of cardiovascular health is needed to address this important limitation of current risk estimators.

Are return-to-play times longer in lower-limb muscle injuries involving the intramuscular tendon? A systematic review.

OBJECTIVES: To determine the influence of severity and direction (craniocaudal length vs cross-sectional area) of intramuscular tendon tears in the lower limb on return-to-play times, compared to muscle injuries without intramuscular tendon involvement. DESIGN: Systematic review with meta-analysis. METHODS: AMED, CINAHL, SPORTDiscus, ScienceDirect, PubMed (MEDLINE) and Web-of-Science were searched from inception to 31st July 2023, retrieving 666 records, of which nine were deemed eligible. A random-effects meta-analysis was performed on time to return-to-play for British Athletics Muscle Injury Classification 'b' vs 'c'. RESULTS: On the Quality in Prognosis Studies tool, one study had low risk of bias and eight had high risk. Using a best-evidence synthesis, no strong evidence emerged for a difference in time to return-to-play between injuries with or without intramuscular tendon involvement. Moderate evidence was found for an association between increased return-to-play time and the presence of "waviness" on magnetic resonance imaging and loss of tendon tension, but no association with longitudinal extent of tendon involvement. Pooled analysis revealed a medium effect-size difference between British Athletics Muscle Injury Classification 'b' and 'c' injuries, favouring classification 'b' (Hedges g = 0.67; 95% confidence interval 0.20 to 1.15; P = 0.002). CONCLUSIONS: It remains difficult to provide an accurate prognosis for muscle injuries involving the intramuscular tendon due to high risk of bias and moderate heterogeneity across studies. Moderate evidence favoured the prognosis for injuries at the musculotendinous junction (British Athletics Muscle Injury Classification 'b') over intratendinous injuries (British Athletics Muscle Injury Classification 'c').

Regional habitat suitability for aquatic and terrestrial invasive plant species may expand or contract with climate change.

The threat of invasive species to biodiversity and ecosystem structure is exacerbated by the increasingly concerning outlook of predicted climate change and other human influences. Developing preventative management strategies for invasive plant species before they establish is crucial for effective management. To examine how climate change may impact habitat suitability, we modeled the current and future habitat suitability of two terrestrial species, Geranium lucidum and Pilosella officinarum, and two aquatic species, Butomus umbellatus and Pontederia crassipes, that are relatively new invasive plant species regionally, and are currently spreading in the Pacific Northwest (PNW, North America), an area of unique natural areas, vibrant economic activity, and increasing human population. Using North American presence records, downscaled climate variables, and human influence data, we developed an ensemble model of six algorithms to predict the potential habitat suitability under current conditions and projected climate scenarios RCP 4.5, 7.0, and 8.5 for 2050 and 2080. One terrestrial species (P. officinarum) showed declining habitat suitability in future climate scenarios (contracted distribution), while the other terrestrial species (G. lucidum) showed increased suitability over much of the region (expanded distribution overall). The two aquatic species were predicted to have only moderately increased suitability, suggesting aquatic plant species may be less impacted by climate change. Our research provides a template for regional-scale modelling of invasive species of concern, thus assisting local land managers and practitioners to inform current and future management strategies and to prioritize limited available resources for species with expanding ranges. Supplementary Information: The online version contains supplementary material available at 10.1007/s10530-023-03139-8.

Menstrual cycle hormones and oral contraceptives: a multimethod systems physiology-based review of their impact on key aspects of female physiology.

Hormonal changes around ovulation divide the menstrual cycle (MC) into the follicular and luteal phases. In addition, oral contraceptives (OCs) have active (higher hormone) and placebo phases. Although there are some MC-based effects on various physiological outcomes, we found these differences relatively subtle and difficult to attribute to specific hormones, as estrogen and progesterone fluctuate rather than operating in a complete on/off pattern as observed in cellular or preclinical models often used to substantiate human data. A broad review reveals that the differences between the follicular and luteal phases and between OC active and placebo phases are not associated with marked differences in exercise performance and appear unlikely to influence muscular hypertrophy in response to resistance exercise training. A systematic review and meta-analysis of substrate oxidation between MC phases revealed no difference between phases in the relative carbohydrate and fat oxidation at rest and during acute aerobic exercise. Vascular differences between MC phases are also relatively small or nonexistent. Although OCs can vary in composition and androgenicity, we acknowledge that much more work remains to be done in this area; however, based on what little evidence is currently available, we do not find compelling support for the notion that OC use significantly influences exercise performance, substrate oxidation, or hypertrophy. It is important to note that the study of females requires better methodological control in many areas. Previous studies lacking such rigor have contributed to premature or incorrect conclusions regarding the effects of the MC and systemic hormones on outcomes. While we acknowledge that the evidence in certain research areas is limited, the consensus view is that the impact of the MC and OC use on various aspects of physiology is small or nonexistent.

Oral inflammatory load predicts vascular function in a young adult population: a pilot study.

Background: The periodontium is a highly vascularized area of the mouth, and periodontitis initiates negative functional and structural changes in the vasculature. However, mild oral inflammation, including levels experienced by many apparently healthy individuals, has an unclear impact on cardiovascular function. The purpose of this pilot study is to investigate the effects of objectively measured whole mouth oral inflammatory load (OIL) on vascular function in apparently healthy individuals. Methods: In this cross-sectional and correlational analysis, we recruited 28 young (18-30 years) and systemically healthy participants (16 male, 12 female). Using oral neutrophil counts, a validated measure for OIL, we collected participant's mouth rinse samples and quantified OIL. Blood pressure, arterial stiffness (pulse-wave velocity) and endothelial function (brachial artery flow-mediated dilation) were also measured. Results: Only oral neutrophil count significantly predicted flow-mediated dilation % (p = 0.04; R2 = 0.16, ß = - 1.05) and those with OIL levels associated with >2.5 × 105 neutrophil counts (n = 8) had a lower flow-mediated dilation % (6.0 ± 2.3%) than those with counts associated with gingival health with less than 2.5 × 105 neutrophil counts (10.0 ± 5.2%, p = 0.05). There were no significant predictors for arterial stiffness. Conclusion: We found that OIL was a predictor of reduced flow-mediated dilation. An impairment in flow-mediated dilation is an indicator of future possible risk of cardiovascular disease-one of the leading causes of death in North America. Therefore, this study provides evidence for the importance of oral health and that OIL may impact endothelial function.

Standards of diabetes care and burden of hypoglycaemia in people with diabetes on peritoneal dialysis: Results from a real-world clinical audit.

There is limited data on the standards of diabetes care in people on peritoneal dialysis (PD). Our aim was to assess the standards of diabetes care and the burden of hypoglycaemia in people with diabetes on PD. We performed a retrospective study at three university hospitals from December 2021 to January 2022. Clinical data were extracted from electronic health records. Diabetes care of people on PD was compared against recommended standards for people with diabetes on haemodialysis (as there are no agreed standards for PD). The degree of hypoglycaemia awareness was assessed by validated questionnaires. A total of 65 adults (15 type 1, 49 type 2 and 1 monogenic-diabetes) with a mean age of 63 (range 29-88) years were evaluated. Of them, 92% had diabetes retinal screening with annual review. In contrast, in this high-risk group for foot disease, only 77% had annual foot reviews. The rates of diabetes specialist reviews were variable between hospitals at 63-94% and 10 (15%) had impaired hypoglycaemia awareness. Of the cohort, 32% had HbA1c within the acceptable range of 58-80 mmol/mol (7.5-8.5%), 21% had HbA1c below 58 mmol/mol (7.5%) and 21% (n = 14) reported at least one hypoglycaemic event per month. Our results indicate variation of care within and between different centres, and the need for improved diabetes care in people on PD. Further work is required to establish agreed standards/recommendations of diabetes care in this population. Our findings highlight the necessity of an integrated multidisciplinary approach to improve the standard of diabetes care for people on PD.

Off-loading and compression therapy strategies to treat diabetic foot ulcers complicated by lower limb oedema: a scoping review.

BACKGROUND: Lower limb oedema is a common co-morbidity in those with diabetes and foot ulceration and is linked with increased amputation risk. There is no current guidance for the treatment of concurrent diabetic foot ulcers and lower limb oedema, leading to uncertainty around the safety and efficacy of combination approaches incorporating offloading and compression therapies. To determine indications and contraindications for such strategies and identify any other supplementary treatment approaches, a scoping review was undertaken to map the evidence relating to off-loading and compression therapy strategies to treat both diabetic foot ulcers and lower limb oedema in combination. METHODS: Following the Joanna Briggs Institute (JBI) and PRISMA - Scoping Review (ScR) guidance, this review included published and unpublished literature from inception to April 2022. Literature was sourced using electronic databases including Cochrane Library, PubMed, CINAHL, AMED; websites; professional journals and reference lists of included literature. Eligible literature discussed the management of both diabetic foot ulceration and lower limb oedema and included at least one of the treatment strategies of interest. Data extraction involved recording any suggested off-loading, compression therapy or supplementary treatment strategies and any suggested indications, contraindications and cautions for their use. RESULTS: Five hundred twenty-two publications were found relating to the management of diabetic foot ulcers with an off-loading strategy or the management of lower limb oedema with compression therapy. 51 publications were eligible for inclusion in the review. The majority of the excluded publications did not discuss the situation where diabetic foot ulceration and lower limb oedema present concurrently. CONCLUSIONS: Most literature, focused on oedema management with compression therapy to conclude that compression therapy should be avoided in the presence of severe peripheral arterial disease. Less literature was found regarding off-loading strategies, but it was recommended that knee-high devices should be used with caution when off-loading diabetic foot ulcers in those with lower limb oedema. Treatment options to manage both conditions concurrently was identified as a research gap. Integrated working between specialist healthcare teams, was the supplementary strategy most frequently recommended. In the absence of a definitive treatment solution, clinicians are encouraged to use clinical reasoning along with support from specialist peers to establish the best, individualised treatment approach for their patients. TRIAL REGISTRATION: Open Science Framework (osf.io/crb78).

Biglycan and reduced glycolysis are associated with breast cancer cell dormancy in the brain.

Exit of quiescent disseminated cancer cells from dormancy is thought to be responsible for metastatic relapse and a better understanding of dormancy could pave the way for novel therapeutic approaches. We used an in vivo model of triple negative breast cancer brain metastasis to identify differences in transcriptional profiles between dormant and proliferating cancer cells in the brain. BGN gene, encoding a small proteoglycan biglycan, was strongly upregulated in dormant cancer cells in vivo. BGN expression was significantly downregulated in patient brain metastases as compared to the matched primary breast tumors and BGN overexpression in cancer cells inhibited their growth in vitro and in vivo. Dormant cancer cells were further characterized by a reduced expression of glycolysis genes in vivo, and inhibition of glycolysis in vitro resulted in a reversible growth arrest reminiscent of dormancy. Our study identified mechanisms that could be targeted to induce/maintain cancer dormancy and thereby prevent metastatic relapse.