005). Neither body mass index (BMI) z-score nor school systolic BP (SBP) z-score could predict HTN by ABPM. Office SBP z-score was associated with 1.74 times increased odds ratio to have HTN in ABPM. Sustained HTN and MH were independent predictors of 24-h PWV after adjustment for age, sex, and BMI z-score. In conclusion, arterial stiffness in children and adolescents was assessed by 24-h PWV associates with mean ambulatory BP. Both school and office BP measurements could not predict HTN in ABPM or increasing PWV. HTN in ABPM was independently associated with the risk of higher PWV compared with normotensive and WCH phenotype.BACKGROUND This study reports the long-term visual and treatment outcomes in a whole-population, orthoptic-delivered pre-school visual screening (PSVS) programme in Scotland and further examines their associations with socioeconomic backgrounds and home circumstances. METHODS Retrospective case review was conducted on 430 children who failed PSVS. Outcome measures included best corrected visual acuity (BCVA), severity of amblyopia (mild, moderate and severe), binocular vision (BV) (normal, poor and none), ophthalmic diagnosis and treatment modalities. Parameters at discharge were compared to those at baseline and were measured against the Scottish index of multiple deprivation (SIMD) and Health plan indicator (HPI), which are indices of deprivation and status of home circumstances. RESULTS The proportion of children with amblyopia reduced from 92.3% (373/404) at baseline to 29.1% (106/364) at discharge (p  less then  0.001). Eighty percent (291/364) had good BV at discharge compared to 29.2% (118/404) at baseline (p  less then  0.001). Children from more socioeconomically deprived areas (OR 2.19, 95% CI 1.01-4.30, p = 0.003) or adverse family backgrounds (OR 3.94, 95% CI 1.99-7.74, p = 0.002) were more likely to attend poorly and/or become lost to follow-up. Children from worse home circumstances were five times more likely to have residual amblyopia (OR 5.37, 95% CI 3.29-10.07, p  less then  0.001) and three times more likely to have poor/no BV (OR 3.41, 95% CI 2.49-4.66, p  less then  0.001) than those from better home circumstances. CONCLUSIONS Orthoptic-delivered PSVS is successful at screening and managing amblyopia. Children from homes requiring social care input are less likely to attend and are more likely to have poorer visual outcomes.Discovering that chytrid fungi cause chytridiomycosis in amphibians represented a paradigm shift in our understanding of how emerging infectious diseases contribute to global patterns of biodiversity loss. In this Review we describe how the use of multidisciplinary biological approaches has been essential to pinpointing the origins of amphibian-parasitizing chytrid fungi, including Batrachochytrium dendrobatidis and Batrachochytrium salamandrivorans, as well as to timing their emergence, tracking their cycles of expansion and identifying the core mechanisms that underpin their pathogenicity. We discuss the development of the experimental methods and bioinformatics toolkits that have provided a fuller understanding of batrachochytrid biology and informed policy and control measures.Neuropathic pain is believed to arise from damage to nociceptive C fibres in diabetic neuropathy (DN). We have utilised corneal confocal microscopy (CCM) to quantify the severity of small nerve fibre damage in relation to the severity of neuropathic pain and quality of life (QoL) in patients with and without painful DN. 30 controls and patients with painful (n = 78) and painless (n = 62) DN underwent assessment of large and small nerve fibre function, CCM, neuropathic symptoms (small fibre neuropathy symptom inventory questionnaire, neuropathic pain scale) and QoL (SF-36, pre-R-ODS and hospital anxiety and depression scale). Patients with painful compared to painless DN, had comparable neurophysiology and vibration perception, but lower corneal nerve fibre density (20.1 ± 0.87 vs. 24.13 ± 0.91, P = 0.005), branch density (44.4 ± 3.31 vs. 57.74 ± 3.98, P = 0.03), length (19.61 ± 0.81 vs. 22.77 ± 0.83, P = 0.01), inferior whorl length (18.03 ± 1.46 vs. 25.1 ± 1.95, P = 0.005) and cold sensation threshold (21.35 ± 0.99 vs. 26.08 ± 0.5, P  less then  0.0001) and higher warm sensation threshold (43.7 ± 0.49 vs. 41.37 ± 0.51, P = 0.004) indicative of small fibre damage. There was a significant association between all CCM parameters and the severity of painful neuropathic symptoms, depression score and QoL. CCM identifies small nerve fibre loss, which correlates with the severity of neuropathic symptoms and reduced QoL in patients with painful diabetic neuropathy.Activated phosphoinositide 3-kinase δ syndrome (APDS) is an autosomal-dominant combined immunodeficiency disorder resulting from pathogenic gain-of-function (GOF) mutations in the PIK3CD gene. Patients with APDS display abnormal T cell homeostasis. However, the mechanisms by which PIK3CD GOF contributes to this feature remain unknown. Here, with a cohort of children with PIK3CD GOF mutations from multiple regions of China and a corresponding CRISPR/Cas9 gene-edited mouse model, we reported that hyperactive PI3Kδ disrupted TNaive cell homeostasis in the periphery by intrinsically promoting the growth, proliferation, and activation of TNaive cells. Our results showed that PIK3CD GOF resulted in loss of the quiescence-associated gene expression profile in naive T cells and promoted naive T cells to overgrow, hyperproliferate and acquire an activated functional status. Naive PIK3CD GOF T cells exhibited an enhanced glycolytic capacity and reduced mitochondrial respiration in the resting or activated state. Blocking glycolysis abrogated the abnormal splenic T cell pool and reversed the overactivated phenotype induced by PIK3CD GOF in vivo and in vitro. These results suggest that enhanced aerobic glycolysis is required for PIK3CD GOF-induced overactivation of naive T cells and provide a potential therapeutic approach for targeting glycolysis to treat patients with APDS as well as other immune disorders.Desmoid-type fibromatosis (DTF, aggressive fibromatosis) is a non-metastasizing mesenchymal neoplasm of deep soft tissue with a tendency towards local recurrence. Genetic alterations affecting canonical Wnt/β-catenin signaling are reported in the majority of DTF. While most sporadic DTF harbor somatic mutations in CTNNB1, germline mutations in adenomatous polyposis coli (APC) are known to occur in hereditary DTF types (FAP, Gardner-Syndrome). Additional single nucleotide variants (SNVs) in AKT1 (E17K) and BRAF (V600E) were reported in pediatric DTF with potential clinical implications. We performed targeted next-generation sequencing (NGS) in a large cohort of 204 formalin-fixed DTF samples, comprising 22 pediatric cases (patients age ≤18 years). The mutational status was correlated with clinicopathological characteristics. Overall, deleterious CTNNB1 mutations were detected in 89% of DTF, most frequently affecting the serine/threonine phosphorylation sites T41 and S45 of β-catenin. While the T41A CTNNB1 mutation was significantly more often identified in the mesenterial localization, DTF originating from extra-intestinal sites more frequently harbored the S45P CTNNB1 alteration. Beyond common mutations in CTNNB1, additional SNVs were demonstrated in 7% of the DTF cohort and in 18% of the pediatric DTF subgroup. The mutational spectrum included deleterious mutations in AKT1 (G311S/D and T312I), ALK (R806H and G924S), AR (A159T), EGFR (P848L), ERBB2 (H174Y), IDH2 (H354Y), KIT (V559D), RET (T1038A), SDHA (R325M), and SDHD (R115W), as characterized by in silico prediction tools. In conclusion, our study indicates that DTF may harbor a broader mutational spectrum beyond CTNNB1 mutations, comprising targetable alterations including the herewith first reported imatinib-sensitive KIT V559D mutation in DTF.The aim of this study was to compare the handgrip strength (HGs), assessed with a cylindrical-shape grip device, of fibromyalgia syndrome (FM) patients with healthy subjects and to demonstrate the relationship between HGs characteristics and disease severity. Consecutive female patients with FM were enrolled and compared to a group of healthy women. The correlations between HGs curve characteristics and disease severity indices were studied through the Spearman’s rho correlation coefficients (rho). The HGs threshold distinguishing the FM presence was determined using the receiver operating characteristic (ROC) curves analysis. Multivariate regression analysis was used in order to assess the contribution of covariates on the HGs. 110 patients (mean age 53.8 ± 12.4 years) and 111 healthy controls have been enrolled. Altogether all parameters related to the analysis of HGs were worse in patients with FM. The HGs cut-off distinguishing the presence of a FM was 14.2 Kg. A negative correlation was found between disease severity indices and peak force (p  less then  0.001). Factors significantly associated with HGs area under the curve (AUC) in multivariate analysis were the Widespread Pain Index (WPI) (p = 0.003) and the revised Fibromyalgia Impact Questionnaire (FIQR) (p = 0.016). HGs is reduced in female FM patients and is inversely related to disease severity. The force-time curves analysis may be used as a complementary tool in the FM assessment and monitoring.Climatic factors can influence the establishment and growth of wood species, but little is known about the effect of these factors on monodominant communities in wetlands. Therefore, we asked how climatic factors, such as ENSO (El Niño-Southern Oscillation), precipitation and flooding, influence growth and establishment of the dominant species Erythrina fusca in the Pantanal. We determined the age of sampled individuals, the age of the population and evaluated the effects of climate on tree growth. We obtained samples for dendrochronological analyses using destructive (seven individuals) and non-destructive methods. We cross-dated and built a chronology, correlating results with climatic factors. We sampled 0.6 ha of the population and separated individuals into diameter classes to determine age based on diameter/age ratio obtained through dendrochronological analyses. We obtained a chronology with individuals up to 34 years old, while in the population sample, the oldest individual was 54 years old. The factors that influenced growth during the study period were precipitation (positive correlation) and El Niño (negative correlation). E. fusca individuals seem to grow more during the period of highest precipitation, and El Niño events reduce precipitation in the Pantanal, resulting in a decrease in the growth of E. fusca individuals. We detected a decrease of young individuals in the last nine years, which seems to be related to the decrease in minimum flood levels. This indicates a future decline in the number of individuals. These results allow us to propose measures to protect these monodominant formations, which mainly involve avoiding further anthropic activities, that could reduce flooding levels.