Perinatal Western-style diet exposure associated with decreased microglial counts throughout the arcuate nucleus of the hypothalamus in Japanese macaques.

Perinatal exposure to a high-fat, high-sugar Western-style diet (WSD) is associated with altered neural circuitry in the melanocortin system. This association may have an underlying inflammatory component, as consumption of a WSD during pregnancy can lead to an elevated inflammatory environment. Our group previously demonstrated that prenatal WSD exposure was associated with increased markers of inflammation in the placenta and fetal hypothalamus in Japanese macaques. In this follow-up study, we sought to determine whether this heightened inflammatory state persisted into the postnatal period, as prenatal exposure to inflammation has been shown to reprogram offspring immune function and long-term neuroinflammation would present a potential means for prolonged disruptions to microglia-mediated neuronal circuit formation. Neuroinflammation was approximated in 1-yr-old offspring by counting resident microglia and peripherally derived macrophages in the region of the hypothalamus examined in the fetal study, the arcuate nucleus (ARC). Microglia and macrophages were immunofluorescently stained with their shared marker, ionized calcium-binding adapter molecule 1 (Iba1), and quantified in 11 regions along the rostral-caudal axis of the ARC. A mixed-effects model revealed main effects of perinatal diet (P = 0.011) and spatial location (P = 0.003) on Iba1-stained cell count. Perinatal WSD exposure was associated with a slight decrease in the number of Iba1-stained cells, and cells were more densely located in the center of the ARC. These findings suggest that the heightened inflammatory state experienced in utero does not persist postnatally. This inflammatory response trajectory could have important implications for understanding how neurodevelopmental disorders progress.NEW & NOTEWORTHY Prenatal Western-style diet exposure is associated with increased microglial activity in utero. However, we found a potentially neuroprotective reduction in microglia count during early postnatal development. This trajectory could inform the timing of disruptions to microglia-mediated neuronal circuit formation. Additionally, this is the first study in juvenile macaques to characterize the distribution of microglia along the rostral-caudal axis of the arcuate nucleus of the hypothalamus. Nearby neuronal populations may be greater targets during inflammatory insults.

Hydrogel dressings for donor sites of split-thickness skin grafts.

BACKGROUND: Donor site wounds of split-thickness skin grafts can be a major cause of morbidity. Choosing the appropriate dressing for these wounds is crucial to successful healing. Various types of dressing are available, including hydrogel dressings. A review of current evidence is required to guide clinical decision-making on the choice of dressing for the treatment of donor sites of split-thickness skin grafts. OBJECTIVES: To assess the effects of hydrogel dressings on donor site wounds following split-thickness skin grafts for wound healing. SEARCH METHODS: In July 2022 we searched the Cochrane Wounds Specialised Register, CENTRAL, MEDLINE, Embase, and CINAHL EBSCO Plus. We also searched clinical trials registries for ongoing and unpublished studies, and scanned reference lists of relevant included studies as well as reviews, meta-analyses, and health technology reports to identify additional studies. There were no restrictions with respect to language, date of publication, or study setting. SELECTION CRITERIA: Randomised controlled trials (RCTs) comparing hydrogel dressings with other types of dressing, topical treatments or no dressing, or with different types of hydrogel dressings in managing donor site wounds irrespective of language and publication status. DATA COLLECTION AND ANALYSIS: Two review authors independently carried out data extraction, risk of bias assessment using the Cochrane risk of bias tool, RoB 1, and quality assessment according to GRADE methodology. MAIN RESULTS: We included two studies (162 participants) in this review. One study with three arms and 101 participants (15 months' duration) was conducted in a children's hospital, and compared hydrogel dressings in the form of Sorbact with Algisite, an alginate dressing and Cuticerin, a smooth acetate gauze impregnated with water-repellent ointment. Another study with two arms and 61 participants (19 months' duration) was conducted in three surgery departments and compared an octenidine-containing hydrogel dressing with an identical non-antimicrobial hydrogel dressing. We identified no studies that compared hydrogel dressings with another therapy such as a topical agent (a topical agent is a cream, an ointment or a solution that is applied directly to the wound), or no dressing, or a combination of hydrogel dressings and another therapy versus another therapy alone. Both studies were at high risk of attrition bias and the second study was also at unclear risk of selection bias. Amorphous hydrogel dressings versus other types of dressings Amorphous hydrogel dressings may increase time to wound healing when compared with alginate (mean difference (MD) 1.67 days, 95% confidence interval (CI) 0.56 to 2.78; 1 study, 69 participants; low-certainty evidence) or Cuticerin dressings (MD 1.67 days, 95% CI 0.55 to 2.79; 1 study, 68 participants; low-certainty evidence). The effect of amorphous hydrogel dressings compared with other types of dressings is uncertain for pain at the donor site and wound complications, including scarring and itching (very low-certainty evidence). No adverse events were reported in any of the groups. The study did not report health-related quality of life or wound infection. Octenidine-based hydrogel dressing versus octenidine-free hydrogel dressing The effect of octenidine-based hydrogel dressings versus octenidine-free hydrogel dressings is uncertain for time to wound healing (MD 0.40, 95% CI 0.28 to 0.52; 1 study, 41 participants) and wound infection, as the certainty of the evidence is very low. The certainty of the evidence is also very low for adverse events, with two participants in the intervention group and one participant in the comparison group reporting adverse events (risk ratio (RR) 0.58, 95% CI 0.06 to 5.89; 1 study, 41 participants). The study did not report donor site pain, health-related quality of life, or wound complications. AUTHORS' CONCLUSIONS: There is insufficient evidence to determine the effect of hydrogel dressings on donor site wounds of split thickness skin grafts compared with other types of dressings. There is a need for adequately powered and well-designed RCTs, with adequate sample sizes, types of populations and subgroups, types of interventions, and outcomes, that compare hydrogel dressings with other treatment options in the treatment of donor site wounds of split-thickness skin grafts.

Sodium hyperaccumulators in the Caryophyllales are characterized by both abnormally large shoot sodium concentrations and [Na]shoot/[Na]root quotients greater than unity.

BACKGROUND AND AIMS: Some Caryophyllales species accumulate abnormally large shoot sodium (Na) concentrations in non-saline environments. It is not known whether this is a consequence of altered Na partitioning between roots and shoots. This paper tests the hypotheses (1) that Na concentrations in shoots ([Na]shoot) and in roots ([Na]root) are positively correlated among Caryophyllales, and (2) that shoot Na hyperaccumulation is correlated with [Na]shoot/[Na]root quotients. METHODS: Fifty two genotypes, representing 45 Caryophyllales species and 4 species from other angiosperm orders, were grown hydroponically in a non-saline, complete nutrient solution. Concentrations of Na in shoots and in roots were determined using inductively coupled plasma mass spectrometry (ICP-MS). KEY RESULTS: Sodium concentrations in shoots and roots were not correlated among Caryophyllales species with normal [Na]shoot, but were positively correlated among Caryophyllales species with abnormally large [Na]shoot. In addition, Caryophyllales species with abnormally large [Na]shoot had greater [Na]shoot/[Na]root than Caryophyllales species with normal [Na]shoot. CONCLUSIONS: Sodium hyperaccumulators in the Caryophyllales are characterized by abnormally large [Na]shoot, a positive correlation between [Na]shoot and [Na]root, and [Na]shoot/[Na]root quotients greater than unity.

Positioning for acute respiratory distress in hospitalised infants and children.

BACKGROUND: Acute respiratory distress syndrome (ARDS) is a significant cause of hospitalisation and death in young children. Positioning and mechanical ventilation have been regularly used to reduce respiratory distress and improve oxygenation in hospitalised patients. Due to the association of prone positioning (lying on the abdomen) with sudden infant death syndrome (SIDS) within the first six months, it is recommended that young infants be placed on their back (supine). However, prone positioning may be a non-invasive way of increasing oxygenation in individuals with acute respiratory distress, and offers a more significant survival advantage in those who are mechanically ventilated. There are substantial differences in respiratory mechanics between adults and infants. While the respiratory tract undergoes significant development within the first two years of life, differences in airway physiology between adults and children become less prominent by six to eight years old. However, there is a reduced risk of SIDS during artificial ventilation in hospitalised infants. Thus, an updated review focusing on positioning for infants and young children with ARDS is warranted. This is an update of a review published in 2005, 2009, and 2012. OBJECTIVES: To compare the effects of different body positions in hospitalised infants and children with acute respiratory distress syndrome aged between four weeks and 16 years. SEARCH METHODS: We searched CENTRAL, which contains the Acute Respiratory Infections Group's Specialised Register, MEDLINE, Embase, and CINAHL from January 2004 to July 2021. SELECTION CRITERIA: Randomised controlled trials (RCTs) or quasi-RCTs comparing two or more positions for the management of infants and children hospitalised with ARDS. DATA COLLECTION AND ANALYSIS: Two review authors independently extracted data from each study. We resolved differences by consensus, or referred to a third contributor to arbitrate. We analysed bivariate outcomes using an odds ratio (OR) and 95% confidence interval (CI). We analysed continuous outcomes using a mean difference (MD) and 95% CI. We used a fixed-effect model, unless heterogeneity was significant (I2 statistic > 50%), when we used a random-effects model. MAIN RESULTS: We included six trials: four cross-over trials, and two parallel randomised trials, with 198 participants aged between 4 weeks and 16 years, all but 15 of whom were mechanically ventilated. Four trials compared prone to supine positions. One trial compared the prone position to good-lung dependent (where the person lies on the side of the healthy lung, e.g. if the right lung was healthy, they were made to lie on the right side), and independent (or non-good-lung independent, where the person lies on the opposite side to the healthy lung, e.g. if the right lung was healthy, they were made to lie on the left side) position. One trial compared good-lung independent to good-lung dependent positions. When the prone (with ventilators) and supine positions were compared, there was no information on episodes of apnoea or mortality due to respiratory events. There was no conclusive result in oxygen saturation (SaO2; MD 0.40 mmHg, 95% CI -1.22 to 2.66; 1 trial, 30 participants; very low certainty evidence); blood gases, PCO2 (MD 3.0 mmHg, 95% CI -1.93 to 7.93; 1 trial, 99 participants; low certainty evidence), or PO2 (MD 2 mmHg, 95% CI -5.29 to 9.29; 1 trial, 99 participants; low certainty evidence); or lung function (PaO2/FiO2 ratio; MD 28.16 mmHg, 95% CI -9.92 to 66.24; 2 trials, 121 participants; very low certainty evidence). However, there was an improvement in oxygenation index (FiO2% X MPAW/ PaO2) with prone positioning in both the parallel trials (MD -2.42, 95% CI -3.60 to -1.25; 2 trials, 121 participants; very low certainty evidence), and the cross-over study (MD -8.13, 95% CI -15.01 to -1.25; 1 study, 20 participants). Derived indices of respiratory mechanics, such as tidal volume, respiratory rate, and positive end-expiratory pressure (PEEP) were reported. There was an apparent decrease in tidal volume between prone and supine groups in a parallel study (MD -0.60, 95% CI -1.05 to -0.15; 1 study, 84 participants; very low certainty evidence). When prone and supine positions were compared in a cross-over study, there were no conclusive results in respiratory compliance (MD 0.07, 95% CI -0.10 to 0.24; 1 study, 10 participants); changes in PEEP (MD -0.70 cm H2O, 95% CI -2.72 to 1.32; 1 study, 10 participants); or resistance (MD -0.00, 95% CI -0.05 to 0.04; 1 study, 10 participants). One study reported adverse events. There were no conclusive results for potential harm between groups in extubation (OR 0.57, 95% CI 0.13 to 2.54; 1 trial, 102 participants; very low certainty evidence); obstructions of the endotracheal tube (OR 5.20, 95% CI 0.24 to 111.09; 1 trial, 102 participants; very low certainty evidence); pressure ulcers (OR 1.00, 95% CI 0.41 to 2.44; 1 trial, 102 participants; very low certainty evidence); and hypercapnia (high levels of arterial carbon dioxide; OR 3.06, 95% CI 0.12 to 76.88; 1 trial, 102 participants; very low certainty evidence). One study (50 participants) compared supine positions to good-lung dependent and independent positions. There was no conclusive evidence that PaO2 was different between supine and good-lung dependent positioning (MD 3.44 mm Hg, 95% CI -23.12 to 30.00; 1 trial, 25 participants; very low certainty evidence). There was also no conclusive evidence for supine position and good-lung independent positioning (MD -2.78 mmHg, 95% CI -28.84, 23.28; 25 participants; very low certainty evidence); or between good-lung dependent and independent positioning (MD 6.22, 95% CI -21.25 to 33.69; 1 trial, 25 participants; very low certainty evidence). As most trials did not describe how possible biases were addressed, the potential for bias in these findings is unclear. AUTHORS' CONCLUSIONS: Although included studies suggest that prone positioning may offer some advantage, there was little evidence to make definitive recommendations. There appears to be low certainty evidence that positioning improves oxygenation in mechanically ventilated children with ARDS. Due to the increased risk of SIDS with prone positioning and lung injury with artificial ventilation, it is recommended that hospitalised infants and children should only be placed in this position while under continuous cardiorespiratory monitoring.

The online version of an evidence-based hand exercise program for people with rheumatoid arthritis: A mixed-method, proof-of-concept study.

INTRODUCTION: The Strengthening And stretching for Rheumatoid Arthritis of the Hand (SARAH) program is a tailored, 12-week hand and arm exercise program recommended in the National Institute for Health and Care Excellence guidelines. It includes seven mobility exercises and four strength exercises against resistance. An online version of the SARAH program (mySARAH) has been developed to allow direct access for people with rheumatoid arthritis. PURPOSE: The purpose of this study was to assess the feasibility, acceptability, and clinical impact of mySARAH in people with rheumatoid arthritis. STUDY DESIGN: This is a mixed-method, proof-of-concept study. METHODS: mySARAH is a self-guided, online version of the SARAH program with six exercise training and review sessions. Participants were observed as they worked through four of the six online sessions. They were also asked to demonstrate the SARAH exercises. Participants undertook two sessions independently at home. At the baseline and 12 weeks, hand pain, hand function, and grip strength were measured. At 12 weeks, feedback on mySARAH, and perceived recovery were also collected. Approximately one month later, a telephone follow-up was conducted to explore participants' experiences with mySARAH. Pain, hand function, and perceived recovery were also assessed. RESULTS: Eleven participants (males/females: 3/8) with a median (interquartile range) age of 63 (17) years took part. Six participants completed all mySARAH sessions. About 512 exercise and load-setting demonstrations were observed and 491 (96%) were performed correctly. Improvements in grip strength and hand function were observed with no increase in pain. Most of the participants reported improvement and provided positive feedback. All participants perceived mySARAH as a useful resource. Features to improve the online exercise diary such as recording and tracking exercise dose and face-to-face or remote support by phone or Skype from health professionals were suggested to optimize user engagement. CONCLUSIONS: Initial evaluation of mySARAH indicates that mySARAH was feasible, acceptable, and beneficial to participants. Further iteration and evaluation are needed before large-scale implementation.

Diagnostic accuracy of narrow-band imaging endoscopy with targeted biopsies compared with standard endoscopy with random biopsies in patients with Barrett's esophagus: A systematic review and meta-analysis.

BACKGROUND AND AIM: Endoscopic surveillance for dysplasia in Barrett's esophagus (BE) with random biopsies is the primary diagnostic tool for monitoring clinical progression into esophageal adenocarcinoma. As an alternative, narrow-band imaging (NBI) endoscopy offers targeted biopsies that can improve dysplasia detection. This study aimed to evaluate NBI-guided targeted biopsies' diagnostic accuracy for detecting dysplasia in patients undergoing endoscopic BE surveillance compared with the widely used Seattle protocol. METHODS: Cochrane DTA Register, MEDLINE/PubMed, EMBASE, OpenGrey, and bibliographies of identified papers were searched until 2018. Two independent investigators resolved discrepancies by consensus, study selection, data extraction, and quality assessment. Data on sensitivity, specificity, and predictive values were pooled and analyzed using a random-effects model. RESULTS: Of 9528 identified articles, six studies comprising 493 participants were eligible for quantitative synthesis. NBI-targeted biopsy showed high diagnostic accuracy in detection of dysplasia in BE with a sensitivity of 76% (95% confidence interval [CI]: 0.61-0.91), specificity of 99% (95% CI: 0.99-1.00), positive predictive value of 97% (95% CI: 0.96-0.99), and negative predictive value of 84% (95% CI: 0.69-0.99) for detection of all grades of dysplasia. The receiver-operating characteristic curve for NBI model performance was 0.8550 for detecting all dysplasia. CONCLUSION: Narrow-band imaging-guided biopsy demonstrated high diagnostic accuracy and might constitute a valid substitute for random biopsies during endoscopic surveillance for dysplasia in BE.

Maternal Interleukin-6 Is Associated With Macaque Offspring Amygdala Development and Behavior.

Human and animal cross-sectional studies have shown that maternal levels of the inflammatory cytokine interleukin-6 (IL-6) may compromise brain phenotypes assessed at single time points. However, how maternal IL-6 associates with the trajectory of brain development remains unclear. We investigated whether maternal IL-6 levels during pregnancy relate to offspring amygdala volume development and anxiety-like behavior in Japanese macaques. Magnetic resonance imaging (MRI) was administered to 39 Japanese macaque offspring (Female: 18), providing at least one or more time points at 4, 11, 21, and 36 months of age with a behavioral assessment at 11 months of age. Increased maternal third trimester plasma IL-6 levels were associated with offspring's smaller left amygdala volume at 4 months, but with more rapid amygdala growth from 4 to 36 months. Maternal IL-6 predicted offspring anxiety-like behavior at 11 months, which was mediated by reduced amygdala volumes in the model's intercept (i.e., 4 months). The results increase our understanding of the role of maternal inflammation in the development of neurobehavioral disorders by detailing the associations of a commonly examined inflammatory indicator, IL-6, on amygdala volume growth over time, and anxiety-like behavior.

Characteristics of L-PRP preparations for treating Achilles tendon rupture within the PATH-2 study.

Platelet-rich plasma (PRP) is an autologous preparation that has been claimed to improve healing and mechanobiological properties of tendons both in vitro and in vivo. In this sub-study from the PATH-2 (PRP in Achilles Tendon Healing-2) trial, we report the cellular and growth factor content and quality of the Leukocyte-rich PRP (L-PRP) (N = 103) prepared using a standardized commercial preparation method across 19 different UK centers. Baseline whole blood cell counts (red cells, leukocyte and platelets) demonstrated that the two groups were well-matched. L-PRP analysis gave a mean platelet count of 852.6 x 109/L (SD 438.96), a mean leukocyte cell count of 15.13 x 109/L (SD 10.28) and a mean red blood cell count of 0.91 x 1012/L (SD 1.49). The activation status of the L-PRP gave either low or high expression levels of the degranulation marker CD62p before and after ex-vivo platelet activation respectively. TGF-ß, VEGF, PDGF, IGF and FGFb mean concentrations were 131.92 ng/ml, 0.98 ng/ml, 55.34 ng/ml, 78.2 ng/ml and 111.0 pg/ml respectively with expected correlations with both platelet and leukocyte counts. While PATH-2 results demonstrated that there was no evidence L-PRP is effective for improving clinical outcomes at 24 weeks after Achilles tendon rupture, our findings support that the majority of L-PRP properties were within the method specification and performance.

GeneLiFT: A novel test to facilitate rapid screening of genetic literacy in a diverse population undergoing genetic testing.

With the broader introduction of genomic medicine in research and clinical care, an increasing number of persons are offered genetic testing. Many factors, including genetic literacy, may impact the utilization of genetic results by patients and their families. We developed a rapid, self-administered measure of genetic literacy, called Genetic Literacy Fast Test (GeneLiFT). We next evaluated the association of GeneLiFT scores with the comprehension of limitations of genomic medicine in participants undergoing genetic testing in the NIH-sponsored eMERGE III study at Columbia University Irving Medical Center, New York. All participants underwent genetic screening for variants in 74 actionable genes associated with adult-onset disorders. A diverse cohort of 724 participants completed the survey (60% women, 45% less than 40 years old, and 53% self-reported White non-Hispanic ancestry). The GeneLiFT was validated using known group differences based on education, health literacy, and numeracy, and with questions assessing genetic knowledge. GeneLiFT identified multiple standard genetics terms, that is, jargon, not recognized by more than 50% of participants (including actionability and pathogenicity). Low genetic literacy, identified in 210 participants (29%), was significantly associated with poor understanding of the limitations of genetic testing (p-values < 10-9 ). This association was independent of education, health literacy, and numeracy levels, highlighting the importance of directly measuring genetic literacy. Low genetic literacy was also associated with low satisfaction with the informed consent process. GeneLiFT is a practical tool for rapid assessment of genetic literacy in large studies or clinical care. GeneLiFT will allow future research to efficiently assess the role of genetic literacy on the clinical impact of genetic testing.

Effect of phosphorus supply on root traits of two Brassica oleracea L. genotypes.

BACKGROUND: Phosphorus (P) deficiency limits crop production worldwide. Crops differ in their ability to acquire and utilise the P available. The aim of this study was to determine root traits (root exudates, root system architecture (RSA), tissue-specific allocation of P, and gene expression in roots) that (a) play a role in P-use efficiency and (b) contribute to large shoot zinc (Zn) concentration in Brassica oleracea. RESULTS: Two B. oleracea accessions (var. sabellica C6, a kale, and var. italica F103, a broccoli) were grown in a hydroponic system or in a high-throughput-root phenotyping (HTRP) system where they received Low P (0.025 mM) or High P (0.25 mM) supply for 2 weeks. In hydroponics, root and shoot P and Zn concentrations were measured, root exudates were profiled using both Fourier-Transform-Infrared spectroscopy and gas-chromatography-mass spectrometry and previously published RNAseq data from roots was re-examined. In HTRP experiments, RSA (main and lateral root number and lateral root length) was assessed and the tissue-specific distribution of P was determined using micro-particle-induced-X-ray emission. The C6 accession had greater root and shoot biomass than the F103 accession, but the latter had a larger shoot P concentration than the C6 accession, regardless of the P supply in the hydroponic system. The F103 accession had a larger shoot Zn concentration than the C6 accession in the High P treatment. Although the F103 accession had a larger number of lateral roots, which were also longer than in the C6 accession, the C6 accession released a larger quantity and number of polar compounds than the F103 accession. A larger number of P-responsive genes were found in the Low P treatment in roots of the F103 accession than in roots of the C6 accession. Expression of genes linked with "phosphate starvation" was up-regulated, while those linked with iron homeostasis were down-regulated in the Low P treatment. CONCLUSIONS: The results illustrate large within-species variability in root acclimatory responses to P supply in the composition of root exudates, RSA and gene expression, but not in P distribution in root cross sections, enabling P sufficiency in the two B. oleracea accessions studied.

Evaluation of the cost and effectiveness of diverse recruitment methods for a genetic screening study.

PURPOSE: Recruitment of participants from diverse backgrounds is crucial to the generalizability of genetic research, but has proven challenging. We retrospectively evaluated recruitment methods used for a study on return of genetic results. METHODS: The costs of study design, development, and participant enrollment were calculated, and the characteristics of the participants enrolled through the seven recruitment methods were examined. RESULTS: A total of 1118 participants provided consent, a blood sample, and questionnaire data. The estimated cost across recruitment methods ranged from $579 to $1666 per participant and required a large recruitment team. Recruitment methods using flyers and staff networks were the most cost-efficient and resulted in the highest completion rate. Targeted sampling that emphasized the importance of Latino/a participation, utilization of translated materials, and in-person recruitments contributed to enrolling a demographically diverse sample. CONCLUSIONS: Although all methods were deployed in the same hospital or neighborhood and shared the same staff, each recruitment method was different in terms of cost and characteristics of the enrolled participants, suggesting the importance of carefully choosing the recruitment methods based on the desired composition of the final study sample. This analysis provides information about the effectiveness and cost of different methods to recruit adults for genetic research.

Correction: Evaluation of the cost and effectiveness of diverse recruitment methods for a genetic screening study.

The original version of this Article contained an error in the undergraduate degree awarded to the author Ian Halim, which was incorrectly given as BS. This has now been corrected to BA in both the PDF and HTML versions of the Article.

The effect of saffron on weight and lipid profile: A systematic review, meta-analysis, and dose-response of randomized clinical trials.

Plant derivatives such as carotenoids and phytosterols enrich foods have been shown to reduce plasma triglyceride (TG), low-density lipoprotein (LDL) cholesterol, and cholesterol concentrations. The aim of this systematic review and meta-analyses study was to investigate the effects of saffron on lipid profiles, reported in randomized controlled trials (RCTs). We performed a systematic electronic search in PubMed/MEDLINE, Cochrane, and SCOPUS to identify RCTs and screening of relevant articles references up to October 12, 2018. There were no language restrictions. We performed this systematic review and meta-analysis according to the Preferred Items for Reporting of Systematic Reviews and Meta-Analyses guidelines. We identified and analyzed 14 eligible studies in this meta-analysis. Our study found a significant reduction in cholesterol and TG following saffron intervention (weighted mean difference [WMD]: -6.36 mg/dl, 95% confidence interval, CI, [-10.58, -2.18] and WMD: -5.37 mg/dl, 95% CI [-10.25, -0.48], respectively). There was no significant effect on weight and LDL concentration. A meta-regression analysis showed that long-term saffron intervention can increase the high-density lipoprotein (HDL) levels. In conclusions, our study findings indicate some benefits of saffron on cholesterol, HDL, and TG compared with placebo. However, we recommend the conduct of adequately powered, high-quality RCTs with short- and long-term follow-up, evaluating relevant clinical outcomes to allow for making definitive recommendations.

Evolutionary origins of abnormally large shoot sodium accumulation in nonsaline environments within the Caryophyllales.

The prevalence of sodium (Na)-'hyperaccumulator' species, which exhibit abnormally large shoot sodium concentrations ([Na]shoot ) when grown in nonsaline environments, was investigated among angiosperms in general and within the Caryophyllales order in particular. Shoot Na concentrations were determined in 334 angiosperm species, representing 35 orders, grown hydroponically in a nonsaline solution. Many Caryophyllales species exhibited abnormally large [Na]shoot when grown hydroponically in a nonsaline solution. The bimodal distribution of the log-normal [Na]shoot of species within the Caryophyllales suggested at least two distinct [Na]shoot phenotypes within this order. Mapping the trait of Na-hyperaccumulation onto the phylogenetic relationships between Caryophyllales families, and between subfamilies within the Amaranthaceae, suggested that the trait evolved several times within this order: in an ancestor of the Aizoaceae, but not the Phytolaccaceae or Nyctaginaceae, in ancestors of several lineages formerly classified as Chenopodiaceae, but not in the Amaranthaceae sensu stricto, and in ancestors of species within the Cactaceae, Portulacaceae, Plumbaginaceae, Tamaricaceae and Polygonaceae. In conclusion, a disproportionate number of Caryophyllales species behave as Na-hyperaccumulators, and multiple evolutionary origins of this trait can be identified within this order.

Prognostic factors for recovery following acute lateral ankle ligament sprain: a systematic review.

BACKGROUND: One-third of individuals who sustain an acute lateral ankle ligament sprain suffer significant disability due to pain, functional instability, mechanical instability or recurrent sprain after recovery plateaus at 1 to 5 years post injury. The identification of early prognostic factors associated with poor recovery may provide an opportunity for early-targeted intervention and improve outcome. METHODS: We performed a comprehensive search of AMED, EMBASE, Psych Info, CINAHL, SportDiscus, PubMed, CENTRAL, PEDro, OpenGrey, abstracts and conference proceedings from inception to September 2016. Prospective studies investigating the association between baseline prognostic factors and recovery over time were included. Two independent assessors performed the study selection, data extraction and quality assessment of the studies. A narrative synthesis is presented due to inability to meta-analyse results due to clinical and statistical heterogeneity. RESULTS: The search strategy yielded 3396 titles/abstracts after duplicates were removed. Thirty-six full text articles were then assessed, nine of which met the study inclusion criteria. Six were prospective cohorts, and three were secondary analyses of randomised controlled trials. Results are presented for nine studies that presented baseline prognostic factors for recovery after an acute ankle sprain. Age, female gender, swelling, restricted range of motion, limited weight bearing ability, pain (at the medial joint line and on weight-bearing dorsi-flexion at 4 weeks, and pain at rest at 3 months), higher injury severity rating, palpation/stress score, non-inversion mechanism injury, lower self-reported recovery, re-sprain within 3 months, MRI determined number of sprained ligaments, severity and bone bruise were found to be independent predictors of poor recovery. Age was one prognostic factor that demonstrated a consistent association with outcome in three studies, however cautious interpretation is advised. CONCLUSIONS: The associations between prognostic factors and poor recovery after an acute lateral ankle sprain are largely inconclusive. At present, there is insufficient evidence to recommend any factor as an independent predictor of outcome. There is a need for well-conducted prospective cohort studies with adequate sample size and long-term follow-up to provide robust evidence on prognostic factors of recovery following an acute lateral ankle sprain. TRIAL REGISTRATION: Prospero registration: CRD42014014471.

The burden of road traffic crashes, injuries and deaths in Africa: a systematic review and meta-analysis.

OBJECTIVE: To estimate the burden of road traffic injuries and deaths for all road users and among different road user groups in Africa. METHODS: We searched MEDLINE, EMBASE, Global Health, Google Scholar, websites of African road safety agencies and organizations for registry- and population-based studies and reports on road traffic injury and death estimates in Africa, published between 1980 and 2015. Available data for all road users and by road user group were extracted and analysed. We conducted a random-effects meta-analysis and estimated pooled rates of road traffic injuries and deaths. FINDINGS: We identified 39 studies from 15 African countries. The estimated pooled rate for road traffic injury was 65.2 per 100 000 population (95% confidence interval, CI: 60.8-69.5) and the death rate was 16.6 per 100 000 population (95% CI: 15.2-18.0). Road traffic injury rates increased from 40.7 per 100 000 population in the 1990s to 92.9 per 100 000 population between 2010 and 2015, while death rates decreased from 19.9 per 100 000 population in the 1990s to 9.3 per 100 000 population between 2010 and 2015. The highest road traffic death rate was among motorized four-wheeler occupants at 5.9 per 100 000 population (95% CI: 4.4-7.4), closely followed by pedestrians at 3.4 per 100 000 population (95% CI: 2.5-4.2). CONCLUSION: The burden of road traffic injury and death is high in Africa. Since registry-based reports underestimate the burden, a systematic collation of road traffic injury and death data is needed to determine the true burden.

Better together? The cognitive advantages of synaesthesia for time, numbers, and space.

Synaesthesia for time, numbers, and space (TNS synaesthesia) is thought to have costs and benefits for recalling and manipulating time and number. There are two competing theories about how TNS synaesthesia affects cognition. The "magnitude" account predicts that TNS synaesthesia may affect cardinal magnitude judgements, whereas the "sequence" account suggests that it may affect ordinal sequence judgements and could rely on visuospatial working memory. We aimed to comprehensively assess the cognitive consequences of TNS synaesthesia and distinguish between these two accounts. TNS synaesthetes, grapheme-colour synaesthetes, and nonsynaesthetes completed a behavioural task battery. Three tasks involved cardinal and ordinal comparisons of temporal, numerical, and spatial stimuli; we also examined visuospatial working memory. TNS synaesthetes were significantly more accurate than nonsynaesthetes in making ordinal judgements about space. This difference was explained by significantly higher visuospatial working memory accuracy. Our findings demonstrate an advantage of TNS synaesthesia that is more in line with the sequence account.

Dual Incontinence and Risk of Fall: A Retrospective Cohort Study.

IMPORTANCE: Although there is a known association between urinary incontinence (UI) and fall risk, it is unclear if having both UI and fecal incontinence, or dual incontinence (DI), increases this risk. OBJECTIVE: The objective of our study was to elucidate a relationship between DI and falls. STUDY DESIGN: This was a retrospective cohort study at a tertiary academic health system of female patients 65 years and older presenting for a new patient visit to a urogynecology health care professional for UI from 2019 to 2021. Demographic data and responses to intake questionnaires on fall and markers of frailty were extracted. Multivariable logistic regression was performed to identify factors associated with fall adjusting for covariates identified upon univariate comparison. RESULTS: A total of 2,814 women were included in the analysis; 2,661 patients reported UI alone, and 153 reported DI. A greater proportion of women with DI reported a fall in the past year compared with those with UI alone (22.9% vs 12.2%, P < 0.001). Univariable comparison showed that these 2 groups differed regarding age, body mass index, and estimated median household income. On multivariable logistic regression, DI was significantly associated with falls (adjusted odds ratio 2.56; 95% confidence interval, 1.02-5.46). Other factors independently associated with falls in older women with UI include (adjusted odds ratio, 95% confidence interval): lower income groups (2.35, 1.50-3.67 for $20,000-$40,000, compared with $100,000 and higher-income group), difficulty with activities of daily living (1.60, 1.25-2.13), and unintentional weight loss (1.68, 1.05-2.68). CONCLUSION: Patients with DI have a 2-fold higher risk of fall compared with patients with UI alone.

Statistical analysis plan for cluster randomised trial to evaluate a community-level complementary food safety and hygiene and nutrition intervention in Mali: the MaaCiwara study.

BACKGROUND: Diarrheal disease is a significant cause of morbidity and mortality in under-fives in many low- and middle-income countries. Changes in food safety, hygiene practices, and nutrition around the weaning period may reduce the risk of disease and improve infant development. The MaaCiwara study aims to evaluate the effectiveness of a community-based educational intervention designed to improve food safety and hygiene behaviours, as well as child nutrition. This update article describes the statistical analysis plan for the MaaCiwara study in detail. METHODS AND DESIGN: The MaaCiwara study is a parallel group, two-arm, superiority cluster randomised controlled trial with baseline measures, involving 120 clusters of rural and urban communities. These clusters are randomised to either receive the community-based behaviour change intervention or to the control group. The study participants will be mother-child pairs, with children aged between 6 and 36 months. Data collection involves a day of observation and interviews with each participating mother-child pair, conducted at baseline, 4 months, and 15 months post-intervention. The primary analysis aims to estimate the effectiveness of the intervention on changes to complementary food safety and preparation behaviours, food and water contamination, and diarrhoea. The primary outcomes will be analysed generalised linear mixed models, at individual level, accounting for clusters and rural/urban status to estimate the difference in outcomes between the intervention and control groups. Secondary outcomes include maternal autonomy, enteric infection, nutrition, child anthropometry, and development scores. In addition, structural equation analysis will be conducted to examine the causal relationships between the different outcomes. TRIAL REGISTRATION: International Standard Randomised Controlled Trial Number (ISRCTN) register: ISRCTN14390796 . Registered on 13 December 2021.

Spatiotemporal Mapping and Molecular Basis of Whole-brain Circuit Maturation.

Brain development is highly dynamic and asynchronous, marked by the sequential maturation of functional circuits across the brain. The timing and mechanisms driving circuit maturation remain elusive due to an inability to identify and map maturing neuronal populations. Here we create DevATLAS (Developmental Activation Timing-based Longitudinal Acquisition System) to overcome this obstacle. We develop whole-brain mapping methods to construct the first longitudinal, spatiotemporal map of circuit maturation in early postnatal mouse brains. Moreover, we uncover dramatic impairments within the deep cortical layers in a neurodevelopmental disorders (NDDs) model, demonstrating the utility of this resource to pinpoint when and where circuit maturation is disrupted. Using DevATLAS, we reveal that early experiences accelerate the development of hippocampus-dependent learning by increasing the synaptically mature granule cell population in the dentate gyrus. Finally, DevATLAS enables the discovery of molecular mechanisms driving activity-dependent circuit maturation.