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A regrowing nail tip after nail avulsion may excessively curve and invaginate into the nail bed. This is treated as a type of ingrown toenail, and is known as distal nail embedding. In most cases, further growth restores the original shape evenly over the nail bed. However, it is often painful and such cases may require treatment. We report a surgical approach that we applied to six cases of distal nail embedding involving pain or deformity of nails caused by a nail tip invaginating into the nail bed and/or cessation of forward nail growth. As our method involves removing a portion of the embedded tip edge nail and inserting the removed nail into the remaining depressed portion, the nail can grow over the bulge. In all six patients in whom we applied this method, the pain and nail deformity resolved and there was no recurrence. We used autogenous nails, which can reduce the pressure imbalance on a nail bed, and this contributed to improving the morphology of nails and nail beds. In addition, the risk of a hypertrophied nail is reduced because half of the nail adheres to the nail bed. Special materials are unnecessary and this method can be conducted with simple outpatient department procedures. There were no cases of a fixed nail section detaching due to a bulge at the nail tip. The inserted nail was maintained in all cases for several months until the nail grew over the bulge.Herein, we disclose osmaelectro-catalyzed C-H activations that set the stage for electrooxidative alkyne annulations by benzoic acids. The osmium electrocatalysis enables site- and chemoselective electrooxidative C-H activations with unique levels of selectivities. The isolation of unprecedented osmium(0) and osmium(II) intermediates, along with crystallographic characterization and analyses by spectrometric and spectroscopic in-operando techniques delineate a synergistic osmium redox catalyst regime. Detailed mechanistic studies revealed a facile C-H cleavage, which allowed for ample substrate scope to provide robust and user-friendly access to annulated heterocycles.Glycoside hydrolase family 15 (GH15) inverting enzymes contain two glutamate residues functioning as a general acid catalyst and a general base catalyst, for isomaltose glucohydrolase (IGHase), Glu178 and Glu335, respectively. Generally, a two-catalytic residue-mediated reaction exhibits a typical bell-shaped pH-activity curve. However, IGHase is found to display atypical non-bell-shaped pH-kcat and pH-kcat /Km profiles, theoretically better-fitted to a three-catalytic residue-associated pH-activity curve. We determined the crystal structure of IGHase by the single-wavelength anomalous dispersion method using sulfur atoms and the cocrystal structure of a catalytic base mutant E335A with isomaltose. Although the activity of E335A was undetectable, the electron density observed in its active site pocket did not correspond to an isomaltose but a glycerol and a β-glucose, cryoprotectant, and hydrolysis product. Our structural and biochemical analyses of several mutant enzymes suggest that Tyr48 acts as a second catalytic base catalyst. Y48F mutant displayed almost equivalent specific activity to a catalytic acid mutant E178A. FB23-2 concentration Tyr48, highly conserved in all GH15 members, is fixed by another Tyr residue in many GH15 enzymes; the latter Tyr is replaced by Phe290 in IGHase. The pH profile of F290Y mutant changed to a bell-shaped curve, suggesting that Phe290 is a key residue distinguishing Tyr48 of IGHase from other GH15 members. Furthermore, F290Y is found to accelerate the condensation of isomaltose from glucose by modifying a hydrogen-bonding network between Tyr290-Tyr48-Glu335. The present study indicates that the atypical Phe290 makes Tyr48 of IGHase unique among GH15 enzymes.
This study aimed to evaluate the association between intrapartum antibiotics (IABX) and asthma and allergic rhinitis among children by ages 6, 8, and 10 years old.

Retrospective cohort.

Data were collected though Kaiser Permanente Northern California's (KPNC) integrated healthcare system. Children were eligible if they were born in a KPNC hospital between 1997 and 2012 and stayed enrolled through age 6.

Modified Poisson regressions with robust error variances were used to estimate risk ratios for IABX and each outcome at each follow-up age during two separate time periods [1997-2004 (n=91,739), 2005-2012 (n=108,314)].

Asthma and allergic rhinitis by ages 6, 8, and 10.

The proportion of women receiving IABX increased drastically over the study period (4% in 1997 to 49% in 2011), while the incidence of asthma (8%) and allergic rhinitis (6%) stayed relatively stable. In adjusted models, risk ratios for the association between IABX and asthma and allergic rhinitis were largely compatible with the null with some slightly elevated risk ratios observed. For births from 1997-2004 risk ratios for asthma were 1.08(1.00, 1.17) at age 6, 1.05(0.97, 1.15) at age 8, and 1.08(0.99, 1.18) at age 10; for births 2005-2012, risk ratios were 1.00(95% CI 0.95, 1.04) at age 6, 1.07(1.01, 1.12) at age 8, and 1.11(1.03, 1.20) at age 10.

Exposure to intrapartum antibiotics is not a strong predictor of childhood asthma or allergic rhinitis risk.
Exposure to intrapartum antibiotics is not a strong predictor of childhood asthma or allergic rhinitis risk.DNA methylation-based biomarkers of ageing (epigenetic clocks) promise to lead to new insights into evolutionary biology of ageing. Relatively little is known about how the natural environment affects epigenetic ageing effects in wild species. In this study, we took advantage of a unique long-term (>40 years) longitudinal monitoring of individual roe deer (Capreolus capreolus) living in two wild populations (Chizé and Trois-Fontaines, France) facing different ecological contexts, to investigate the relationship between chronological age and levels of DNA methylation (DNAm). We generated novel DNA methylation data from n = 94 blood samples, from which we extracted leucocyte DNA, using a custom methylation array (HorvathMammalMethylChip40). We present three DNA methylation-based estimators of age (DNAm or epigenetic age), which were trained in males, females, and both sexes combined. We investigated how sex differences influenced the relationship between DNAm age and chronological age using sex-specific epigenetic clocks. Our results highlight that old females may display a lower degree of biological ageing than males. Further, we identify the main sites of epigenetic alteration that have distinct ageing patterns between the two sexes. These findings open the door to promising avenues of research at the crossroads of evolutionary biology and biogerontology.
To describe prenatal decision-making processes and birth plans in pregnancies amenable to planning perinatal palliative care.

Multicentre prospective observational study.

Nine Multidisciplinary Centres for Prenatal Diagnosis of the Paris-Ile-de-France region.

All cases of major and incurable fetal anomaly where limitation of life-sustaining treatments for the neonate was discussed in the prenatal period between 2015 and 2016.

Cases of congenital defects amenable to perinatal palliative care were prospectively included in each centre. Prenatal diagnosis, decision-making process, type of birth plan, birth characteristics, pregnancy and neonatal outcome were collected prospectively and anonymously.

Final decision reached following discussions in the antenatal period.

We identified 736 continuing pregnancies with a diagnosis of a severe fetal condition eligible for TOP. Perinatal palliative care was considered in 102/736 (13.9%) pregnancies (106 infants); discussions were multidisciplinary in 99/106 (93.4%) cases. Prenatal birth plans involved life-sustaining treatment limitation and comfort care in 73/736 (9.9%) of the pregnancies. The main reason for planning palliative care at birth was short-term inevitable death in 39 cases (53.4%). 76/106 (71.7%) infants were born alive. 18/106 (17%) infants were alive at last follow-up, including 4 with a perinatal palliative care birth plan.

Only a small proportion of severe and incurable fetal disorders were potentially amenable to limitation of life-sustaining interventions. Perinatal palliative care may not be considered as an universal alternative to termination of pregnancy.
Only a small proportion of severe and incurable fetal disorders were potentially amenable to limitation of life-sustaining interventions. Perinatal palliative care may not be considered as an universal alternative to termination of pregnancy.Transcribed ultraconserved regions (T-UCRs) are noncoding RNAs derived from DNA sequences that are entirely conserved across species. Their expression is altered in many tumor types, and, although a role for T-UCRs as regulators of gene expression has been proposed, their functions remain largely unknown. Herein, we describe the epigenetic silencing of the uc.160+ T-UCR in gliomas and mechanistically define a novel RNA-RNA regulatory network in which uc.160+ modulates the biogenesis of several members of the miR-376 cluster. This includes the positive regulation of primary microRNA (pri-miRNA) cleavage and an enhanced A-to-I editing on its mature sequence. As a consequence, the expression of uc.160+ affects the downstream, miR-376-regulated genes, including the transcriptional coregulators RING1 and YY1-binding protein (RYBP) and forkhead box P2 (FOXP2). Finally, we elucidate the clinical impact of our findings, showing that hypermethylation of the uc.160+ CpG island is an independent prognostic factor associated with better overall survival in lower-grade gliomas, highlighting the importance of T-UCRs in cancer pathophysiology.
Data on the long-term outcomes of individuals with hepatitis B virus (HBV) infection who are hepatitis envelope antigen (HBeAg)-negative inactive carriers (ICs) are limited due to small numbers. We compared the long-term prognosis of well-defined ICs with that of age- and gender-matched general population controls.

A total of 526 HBeAg-negative patients who demonstrated alanine aminotransferase (ALT) level ≤40U/L and HBV DNA level ≤4.3 log IU/ml at least three times within 1year after the start of follow-up were enrolled as ICs. Inactive carriers were divided into two groups Group A (n=332), whose ALT level was ≤30U/L and HBV DNA level was ≤3.3 log IU/ml, and Group B (remaining patients, n=194). We determined the long-term prognosis of ICs and compared it with that of general population controls. We also analyzed factors associated with hepatitis B surface antigen (HBsAg) clearance and phase transition in ICs.

There were no significant differences in hepatocellular carcinoma development or all-cause, liver-related, or non-liver-related mortality between Groups A and B. There was no significant difference in all-cause mortality between ICs and the general population. Low HBsAg level (≤3.0 log IU/ml) and the presence of fatty liver were associated with HBsAg clearance and high alpha-fetoprotein level was associated with phase transition.

The long-term prognosis of well-defined ICs was similar to that of general population controls. In addition, the ICs had a high HBsAg clearance rate and low phase transition rate.
The long-term prognosis of well-defined ICs was similar to that of general population controls. In addition, the ICs had a high HBsAg clearance rate and low phase transition rate.
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