A novel RBF-based predictive tool for facial distraction surgery in growing children with syndromic craniosynostosis

PURPOSE: Predicting changes in face shape from corrective surgery is challenging in growing children with syndromic craniosynostosis. A prediction tool mimicking composite bone and skin movement during facial distraction would be useful for surgical audit and planning. To model surgery, we used a radial basis function (RBF) that is smooth and continuous throughout space whilst corresponding to measured distraction at landmarks. Our aim is to showcase the pipeline for a novel landmark-based, RBF-driven simulation for facial distraction surgery in children. METHODS: An individual's dataset comprised of manually placed skin and bone landmarks on operated and unoperated regions. Surgical warps were produced for 'older' monobloc, 'older' bipartition and 'younger' bipartition groups by applying a weighted least-squares RBF fitted to the average landmarks and change vectors. A 'normalisation' warp, from fitting an RBF to craniometric landmark differences from the average, was applied to each dataset before the surgical warp. The normalisation was finally reversed to obtain the individual prediction. Predictions were compared to actual post-operative outcomes. RESULTS: The averaged change vectors for all groups showed skin and bone movements characteristic of the operations. Normalisation for shape-size removed individual asymmetry, size and proportion differences but retained typical pre-operative shape features. The surgical warps removed the average syndromic features. Reversing the normalisation reintroduced the individual's variation into the prediction. The mid-facial regions were well predicted for all groups. Forehead and brow regions were less well predicted. CONCLUSIONS: Our novel, landmark-based, weighted RBF can predict the outcome for facial distraction in younger and older children with a variety of head and face shapes. It can replicate the surgical reality of composite bone and skin movement jointly in one model. The potential applications include audit of existing patient outcomes, and predicting outcome for new patients to aid surgical planning

Rapid Systematic Review: The Impact of Social Isolation and Loneliness on the Mental Health of Children and Adolescents in the Context of COVID-19

OBJECTIVE: Disease containment of COVID-19 has necessitated widespread social isolation. We aimed to establish what is known about how loneliness and disease containment measures impact on the mental health in children and adolescents. METHOD: For this rapid review, we searched MEDLINE, PSYCHINFO, and Web of Science for articles published between 01/01/1946 and 03/29/2020. 20% of articles were double screened using pre-defined criteria and 20% of data was double extracted for quality assurance. RESULTS: 83 articles (80 studies) met inclusion criteria. Of these, 63 studies reported on the impact of social isolation and loneliness on the mental health of previously healthy children and adolescents (n=51,576; mean age 15.3) 61 studies were observational; 18 were longitudinal and 43 cross sectional studies assessing self-reported loneliness in healthy children and adolescents. One of these studies was a retrospective investigation after a pandemic. Two studies evaluated interventions. Studies had a high risk of bias although longitudinal studies were of better methodological quality. Social isolation and loneliness increased the risk of depression, and possibly anxiety at the time loneliness was measured and between 0.25 to 9 years later. Duration of loneliness was more strongly correlated with mental health symptoms than intensity of loneliness. CONCLUSION: Children and adolescents are probably more likely to experience high rates of depression and probably anxiety during and after enforced isolation ends. This may increase as enforced isolation continues. Clinical services should offer preventative support and early intervention where possible and be prepared for an increase in mental health problems

Loneliness and mental health in children and adolescents with pre-existing mental health problems: A rapid systematic review

Objectives: Periods of social isolation are associated with loneliness in children and young people, and loneliness is associated with poor mental and physical health. Children and young people with pre-existing mental health difficulties may be prone to loneliness. Containment of COVID-19 has necessitated widespread social isolation, with unprecedented school closures and restrictions imposed on social interactions. This rapid review aimed to establish what is known about the relationship between loneliness and mental health problems in children and young people with pre-existing mental health problems. Methods: We sought to identify all primary research that examined the cross-sectional and longitudinal associations between loneliness/perceived social isolation and mental health in children and young people with pre-existing mental health problems. We also aimed to identify effective interventions that reduce the adverse impact of loneliness. A rapid systematic search was conducted using MEDLINE, PsycINFO, and Web of Science. Results: Of 4,531 papers screened, 15 included children and young people with pre-existing mental health conditions. These 15 studies included 1,536 children and young people aged between 6 and 23 years with social phobia, anxiety and/or depression, and neurodevelopmental disorders. Loneliness was associated with anxiety and depression both cross-sectionally and prospectively in children and young people with mental health problems and neurodevelopmental conditions. We found preliminary evidence that psychological treatments can help to reduce feelings of loneliness in this population. Conclusions: Loneliness is associated with depression and anxiety in children and young people with pre-existing mental health conditions, and this relationship may be bidirectional. Existing interventions to address loneliness and/or mental health difficulties in other contexts may be applied to this population, although they may need adaptation and testing in younger children and adolescents. Practitioner points: Loneliness is common in children and young people, and during periods of enforced social isolation such as during COVID-19, children and young people report high levels of loneliness (or increased rates of loneliness). The review showed that loneliness is associated, both cross-sectionally and prospectively, in children and young people with mental health problems and also in children and young people with neurodevelopmental conditions, such as autism spectrum disorder. Thus, loneliness is a possible risk factor of which mental health providers should be aware. Maintaining social contact both by direct and by indirect means, especially through the Internet, could be important in mitigating loneliness. Interventions to address loneliness should be further developed and tested to help children and young people with pre-existing mental health problems who are lonely by preventing exacerbation of their mental health difficulties, in particular anxiety and depression

Association between proton pump inhibitor therapy and clostridium difficile infection: a contemporary systematic review and meta-analysis.

Abstract Introduction Emerging epidemiological evidence suggests that proton pump inhibitor (PPI) acid-suppression therapy is associated with an increased risk of Clostridium difficile infection (CDI). Methods Ovid MEDLINE, EMBASE, ISI Web of Science, and Scopus were searched from 1990 to January 2012 for analytical studies that reported an adjusted effect estimate of the association between PPI use and CDI. We performed random-effect meta-analyses. We used the GRADE framework to interpret the findings. Results We identified 47 eligible citations (37 case-control and 14 cohort studies) with corresponding 51 effect estimates. The pooled OR was 1.65, 95% CI (1.47, 1.85), I2 = 89.9%, with evidence of publication bias suggested by a contour funnel plot. A novel regression based method was used to adjust for publication bias and resulted in an adjusted pooled OR of 1.51 (95% CI, 1.26–1.83). In a speculative analysis that assumes that this association is based on causality, and based on published baseline CDI incidence, the risk of CDI would be very low in the general population taking PPIs with an estimated NNH of 3925 at 1 year. Conclusions In this rigorously conducted systemic review and meta-analysis, we found very low quality evidence (GRADE class) for an association between PPI use and CDI that does not support a cause-effect relationship

Lipid Composition Analysis Reveals Mechanisms of Ethanol Tolerance in the Model Yeast Saccharomyces cerevisiae

Saccharomyces cerevisiae is an important unicellular yeast species within the biotechnological and the food and beverage industries. A significant application of this species is the production of ethanol, where concentrations are limited by cellular toxicity, often at the level of the cell membrane. Here, we characterize 61 S. cerevisiae strains for ethanol tolerance and further analyze five representatives with various ethanol tolerances. The most tolerant strain, AJ4, was dominant in coculture at 0 and 10% ethanol. Unexpectedly, although it does not have the highest noninhibitory concentration or MIC, MY29 was the dominant strain in coculture at 6% ethanol, which may be linked to differences in its basal lipidome. Although relatively few lipidomic differences were observed between strains, a significantly higher phosphatidylethanolamine concentration was observed in the least tolerant strain, MY26, at 0 and 6% ethanol compared to the other strains that became more similar at 10%, indicating potential involvement of this lipid with ethanol sensitivity. Our findings reveal that AJ4 is best able to adapt its membrane to become more fluid in the presence of ethanol and that lipid extracts from AJ4 also form the most permeable membranes. Furthermore, MY26 is least able to modulate fluidity in response to ethanol, and membranes formed from extracted lipids are least leaky at physiological ethanol concentrations. Overall, these results reveal a potential mechanism of ethanol tolerance and suggest a limited set of membrane compositions that diverse yeast species use to achieve this. IMPORTANCE Many microbial processes are not implemented at the industrial level because the product yield is poorer and more expensive than can be achieved by chemical synthesis. It is well established that microbes show stress responses during bioprocessing, and one reason for poor product output from cell factories is production conditions that are ultimately toxic to the cells. During fermentative processes, yeast cells encounter culture media with a high sugar content, which is later transformed into high ethanol concentrations. Thus, ethanol toxicity is one of the major stresses in traditional and more recent biotechnological processes. We have performed a multilayer phenotypic and lipidomic characterization of a large number of industrial and environmental strains of Saccharomyces to identify key resistant and nonresistant isolates for future applications

The impact of submaximal exercise during heat and/or hypoxia on the cardiovascular and monocyte HSP72 responses to subsequent (post 24 h) exercise in hypoxia

BACKGROUND: The aims of this study were to describe the cellular stress response to prolonged endurance exercise in acute heat, hypoxia and the combination of heat and hypoxia and to determine whether prior acute exposure to these stressors improved cellular tolerance to a subsequent exercise bout in hypoxia 24 h later. METHODS: Twelve males (age 22 ± 4 years, height 1.77 ± 0.05 m, mass 79 ± 12.9 kg, VO(2) max 3.57 ± 0.7 L · min(-1)) completed four trials (30-min rest, 90-min cycling at 50% normoxic VO(2) max) in normothermic normoxia (NORM; 18°C, F(I)O(2) = 0.21), heat (HEAT; 40°C, 20% RH), hypoxia (HYP; F(I)O(2) = 0.14) or a combination of heat and hypoxia (COM; 40°C, 20% RH, F(I)O(2) = 0.14) separated by at least 7 days. Twenty-four hours after each trial, participants completed a hypoxic stress test (HST; 15-min rest, 60-min cycling at 50% normoxic VO(2) max, F(I)O(2) = 0.14). Monocyte heat shock protein 72 (mHSP72) was assessed immediately before and after each exercise bout. RESULTS: mHSP72 increased post exercise in NORM (107% ± 5.5%, p > 0.05), HYP (126% ± 16%, p < 0.01), HEAT (153% ± 14%, p < 0.01) and COM (161% ± 32%, p < 0.01). mHSP72 had returned to near-resting values 24 h after NORM (97% ± 8.6%) but was elevated after HEAT (130% ± 19%), HYP (118% ± 17%) and COM (131% ± 19%) (p < 0.05). mHSP72 increased from baseline after HST(NORM) (118% ± 12%, p < 0.05), but did not increase further in HST(HEAT), HST(HYP) and HST(COM). CONCLUSIONS: The prior induction of mHSP72 as a result of COM, HEAT and HYP attenuated further mHSP72 induction after HST and was indicative of conferred cellular tolerance

Clarifying the role of three-dimensional transvaginal sonography in reproductive medicine: an evidenced-based appraisal

This overview describes and illustrates the clinical applications of three-dimensional transvaginal sonography in reproductive medicine. Its main applications include assessment of uterine anomalies, intrauterine pathology, tubal patency, polycystic ovaries, ovarian follicular monitoring and endometrial receptivity. It is also useful for detailed evaluation of failed and/or ectopic pregnancy. Three-dimensional color Doppler sonography provides enhanced depiction of uterine, endometrial, and ovarian vascularity

The Maternal-Effect Gene cellular island Encodes Aurora B Kinase and Is Essential for Furrow Formation in the Early Zebrafish Embryo

Females homozygous for a mutation in cellular island (cei) produce embryos with defects in cytokinesis during early development. Analysis of the cytoskeletal events associated with furrow formation reveal that these defects include a general delay in furrow initiation as well as a complete failure to form furrow-associated structures in distal regions of the blastodisc. A linkage mapping-based candidate gene approach, including transgenic rescue, shows that cei encodes the zebrafish Aurora B kinase homologue. Genetic complementation analysis between the cei mutation and aurB zygotic lethal mutations corroborate gene assignment and reveal a complex nature of the maternal-effect cei allele, which appears to preferentially affect a function important for cytokinesis in the early blastomeres. Surprisingly, in cei mutant embryos a short yet otherwise normal furrow forms in the center of the blastodisc. Furrow formation is absent throughout the width of the blastodisc in cei mutant embryos additionally mutant for futile cycle, which lack a spindle apparatus, showing that the residual furrow signal present in cei mutants is derived from the mitotic spindle. Our analysis suggests that partially redundant signals derived from the spindle and astral apparatus mediate furrow formation in medial and distal regions of the early embryonic blastomeres, respectively, possibly as a spatial specialization to achieve furrow formation in these large cells. In addition, our data also suggest a role for Cei/AurB function in the reorganization of the furrow-associated microtubules in both early cleavage- and somite-stage embryos. In accordance with the requirement for cei/aurB in furrow induction in the early cleavage embryo, germ plasm recruitment to the forming furrow is also affected in embryos lacking normal cei/aurB function