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01), indicating the existence of coinfection. The results show high prevalence of these two important zoonoses, alerting to the need of implementing control measures in order to reduce the incidence and risks of sequelae in children.

Adolescents with obesity are less likely to flourish and be academically engaged in comparison to their healthy weight peers. However, it is unknown how participation in physical activity influences flourishing and academic engagement in adolescents with obesity. The current study examined engagement in varying levels of physical activity and the likelihood of flourishing and academic engagement in adolescents with obesity.

Analyses included 26 764 adolescents, ages 10-17 years, from the parent-reported, combined 2016-2017 National Survey of Children's Health. Participants were grouped by physical activity levels (none, low, moderate, daily). Outcome variables included flourishing (finishing tasks, staying calm when faced with a challenge and showing interest in new things) and academic engagement (completing all required homework and caring about doing well in school). Logistic regression models, adjusted for age, sex, race, household income, highest level of education in the household, behavioural conduemically engaged in comparison to their healthy weight peers.

Dimethandrolone (DMA) and 11β-methyl-19-nortestosterone (11β-MNT) are two novel compounds with both androgenic and progestational activity that are under investigation as potential male hormonal contraceptives. Their metabolic effects have never been compared in men.

Assess for changes in insulin sensitivity and adiponectin and compare the metabolic effects of these two novel androgens.

In two clinical trials of DMA undecanoate (DMAU) and 11β-MNT dodecylcarbonate (11β-MNTDC), oral prodrugs of DMA and 11β-MNT, healthy men received drug, or placebo for 28days. Insulin and adiponectin assays were performed on stored samples. Mixed model analyses were performed to compare the effects of the two drugs. Student's t test, or the non-parametric Kruskal-Wallis test as appropriate, was used to evaluate for an effect of active drug versus placebo.

Class effects were seen, with decrease in HDL-C and SHBG, and increase in weight and hematocrit, with no statistically significant differences between the two compounds. No changes in fasting glucose, fasting insulin, or HOMA-IR were seen with either compound. There was a slight decrease in adiponectin with DMAU that was not seen with 11β-MNTDC. An increase in LDL-C was seen with 11β-MNTDC but not with DMAU.

There were no significant changes in insulin resistance after 28days of oral administration of these novel androgens despite a mild increase in weight. MMP inhibitor There may be subtle differences in their metabolic impacts that should be explored in future studies.

Changes in metabolic parameters should be carefully monitored when investigating androgenic compounds.

Changes in metabolic parameters should be carefully monitored when investigating androgenic compounds.

Breast magnetic resonance imaging (MRI) use for surgical staging is increasing, though remains controversial. We aimed to evaluate the accuracy of MRI in surgical decision-making to determine if mastectomy prompted by MRI was appropriate.

A single-centre observational study in Perth, Western Australia, with the inclusion of all preoperative and postoperative studies (e.g. involved margins after breast-conserving surgery) undergoing staging breast MRI from 1 January 2015 to 26 August 2019. A standard protocol using gadolinium contrast was used. link2 The reference standard was postoperative histopathology or, for studies without additional surgery after MRI following breast-conserving surgery, the next and subsequent annual screening episodes. By reviewing the final histopathology, the medical case notes and multidisciplinary team decision process, we evaluated whether the reported MRI disease extent was accurate in prompting an appropriate upgrade to mastectomy. Outcomes are reported with descriptive statistics.

Of 130 cancers staged with MRI; seven were excluded as information was incomplete, 104 were performed preoperatively and 19 postoperatively. The majority (60%) staged lobular carcinoma (invasive 59%, in situ 1%) compared to ductal carcinoma (invasive 31%, in situ 8%). For preoperative MRI, half (54% - 56/104) underwent subsequent mastectomy. Of these, MRI prompted mastectomy in 45% (25/56), all appropriate for disease extent. In the postoperative staging group, two mastectomies were performed, one planned before imaging, the other prompted when MRI diagnosed residual disease and confirmed on histopathology. No false-negative staging MRI was identified.

In our cohort, MRI prompted an upgrade to mastectomy in 21% (26/123), appropriate for cancer extent.

In our cohort, MRI prompted an upgrade to mastectomy in 21% (26/123), appropriate for cancer extent.

The presence of significant liver fibrosis is a key determinant of long-term prognosis in non-alcoholic fatty liver disease (NAFLD). We aimed to develop a novel machine learning algorithm (MLA) to predict fibrosis severity in NAFLD and compared it with the most widely used non-invasive fibrosis biomarkers.

We used a cohort of 553 adults with biopsy-proven NAFLD, who were randomly divided into a training cohort (n=278) for the development of both logistic regression model (LRM) and MLA, and a validation cohort (n=275). Significant fibrosis was defined as fibrosis stage F≥2. MLA and LRM were derived from variables that were selected using a least absolute shrinkage and selection operator (LASSO) logistic regression algorithm.

In the training cohort, the variables selected by LASSO algorithm were body mass index, pro-collagen type III, collagen type IV, aspartate aminotransferase and albumin-to-globulin ratio. The diagnostic accuracy of MLA showed the highest values of area under the receiver operator characteristic curve (AUROC 0.902, 95% CI 0.869-0.904) for identifying fibrosis F≥2. The LRM AUROC was 0.764, 95% CI 0.710-0.816 and significantly better than the AST-to-Platelet ratio (AUROC 0.684, 95% CI 0.605-0.762), FIB-4 score (AUROC 0.594, 95% CI 0.503-0.685) and NAFLD Fibrosis Score (AUROC 0.557, 95% CI 0.470-0.644). link3 In the validation cohort, MLA also showed the highest AUROC (0.893, 95% CI 0.864-0.901). The diagnostic accuracy of MLA outperformed that of LRM in all subgroups considered.

Our newly developed MLA algorithm has excellent diagnostic performance for predicting fibrosis F≥2 in patients with biopsy-confirmed NAFLD.

Our newly developed MLA algorithm has excellent diagnostic performance for predicting fibrosis F ≥ 2 in patients with biopsy-confirmed NAFLD.The present work is the last of a three-part study investigating a panel of 30 systematically designed synthetic cannabinoid receptor agonists (SCRAs) including features such as the 4-pentenyl tail and varying head groups including amides and esters of l-valine (MMB, AB), l-tert-leucine (ADB), and l-phenylalanine (APP), as well as adamantyl (A) and cumyl moieties (CUMYL). Here, we evaluated these SCRAs for their capacity to activate the human cannabinoid receptor 1 (CB1 ) via indirect measurement of G protein recruitment. Furthermore, we comparatively evaluated the results obtained from three in vitro assays, based on the recruitment of β-arrestin 2 (βarr2 assay) or Gαi protein (mini-Gαi assay), or binding of [35 S]-GTPγS. The observed efficacies (Emax ) varied depending on the conducted assay. Statistical analysis suggests that the population means of the relative intrinsic activity (RAi ) significantly differ for the [35 S]-GTPγS assay and the other two assays, but the population means of the βarr2 and mini-Gαi assays were not statistically different. Our data suggest that differences observed between the βarr2 and mini-Gαi assays are the best predictor for 'biased agonism' towards βarr or G protein recruitment in our study. SCRAs carrying an ADB or MPP moiety as a head group tended to produce elevated Emax values in the βarr2 assay, which might result in a tendency of these compounds to cause pronounced tolerance in users-a hypothesis that should be evaluated further by future studies. In general, a comparison of efficacies derived from different assays is difficult and should only be conducted very cautiously.Sleep-disordered breathing (SDB) is common in patients with skeletal dysplasias. The aim of our study was to analyze SDB and respiratory management in children with rare skeletal dysplasias. We performed a retrospective analysis of patients with spondyloepiphyseal dysplasia congenita (SEDC), metatropic dysplasia (MD), spondyloepimetaphyseal dysplasia (SEMD), acrodysostosis (ADO), geleophysic dysplasia (GD), acromicric dysplasia (AD), and spondylocostal dysplasia (SCD) between April 2014 and October 2020. Polygraphic data, clinical management, and patients' outcome were analyzed. Thirty-one patients were included (8 SEDC, 3 MD, 4 SEMD, 1 ADO, 4 GD, 3 AD, and 8 SCD). Sixteen patients had obstructive sleep apnea (OSA) 11 patients (2 with SEDC, 1 with SEMD, 1 with ADO, 1 with GD, 2 with AD, and 4 with SCD) had mild OSA, 2 (1 SEMD and 1 GD) had moderate OSA, and 3 (1 SEDC, 1 MD, 1 SEMD) had severe OSA. Adenotonsillectomy was performed in one patient with SCD and mild OSA, and at a later age in two other patients with ADO and AD. The two patients with moderate OSA were treated with noninvasive ventilation (NIV) because of nocturnal hypoxemia. The three patients with severe OSA were treated with adenotonsillectomy (1 SEDC), adeno-turbinectomy and continuous positive airway pressure (CPAP; 1 MD), and with NIV (1 SEMD) because of nocturnal hypoventilation. OSA and/or alveolar hypoventilation is common in patients with skeletal dysplasias, underlining the importance of systematic screening for SDB. CPAP and NIV are effective treatments for OSA and nocturnal hypoventilation/hypoxemia.While several functional and structural changes occur in large-scale brain networks in autism spectrum disorder (ASD), reduced interhemispheric resting-state functional connectivity (rsFC) between homotopic regions may be of particular importance as a biomarker. ASD is an early-onset developmental disorder and neural alterations are often age-dependent. Although there is some evidence for homotopic interhemispheric rsFC alterations in language processing regions in ASD children, wider analyses using large data sets have not been performed. The present study, therefore, conducted a voxel-based homotopic interhemispheric rsFC analysis in 146 ASD and 175 typically developing children under-age 10 and examined associations with symptom severity in the autism brain imaging data exchange data sets. Given the role of corpus callosum (CC) in interhemispheric connectivity and reported CC volume changes in ASD we additionally examined whether there were parallel volumetric changes. Results demonstrated decreased homotoctivity, suggesting that alterations in homotopic interhemispheric connectivity may occur early in ASD and be a useful general biomarker across ages.Gastric lymphangioma (GLA) is an extremely rare tumor without an established therapeutic strategy. Surgical resection is considered the mainstay of treatment, although there is a high risk of local recurrence if negative margins are not achieved. A 51-year-old man underwent routine abdominal ultrasonography, which incidentally detected a 20-mm tumor adjacent to the lesser curvature of the stomach. GLA was suspected based on its polycystic appearance. After a 16-month monitoring period, laparoscopic resection was performed because of tumor growth and involvement of the left gastric artery. Intraoperative indocyanine green (ICG) navigation system revealed lymphatic drainage from the tumor, which we used to help determine the optimal excision line and minimize the loss of gastric volume. Pathological examination confirmed complete resection with negative margins and supported a diagnosis of lymphangioma. We performed laparoscopic radical resection of GLA under guidance from intraoperative ICG fluorescence imaging, which allowed us to maximize residual gastric volume.