Sex chromosomes and hormones independently influence healthy brain development but act similarly after cranial radiation.

The course of normal development and response to pathology are strongly influenced by biological sex. For instance, female childhood cancer survivors who have undergone cranial radiation therapy (CRT) tend to display more pronounced cognitive deficits than their male counterparts. Sex effects can be the result of sex chromosome complement (XX vs. XY) and/or gonadal hormone influence. The contributions of each can be separated using the four-core genotype mouse model (FCG), where sex chromosome complement and gonadal sex are decoupled. While studies of FCG mice have evaluated brain differences in adulthood, it is still unclear how sex chromosome and sex hormone effects emerge through development in both healthy and pathological contexts. Our study utilizes longitudinal MRI with the FCG model to investigate sex effects in healthy development and after CRT in wildtype and immune-modified Ccl2-knockout mice. Our findings in normally developing mice reveal a relatively prominent chromosome effect prepubertally, compared to sex hormone effects which largely emerge later. Spatially, sex chromosome and hormone influences were independent of one another. After CRT in Ccl2-knockout mice, both male chromosomes and male hormones similarly improved brain outcomes but did so more separately than in combination. Our findings highlight the crucial role of sex chromosomes in early development and identify roles for sex chromosomes and hormones after CRT-induced inflammation, highlighting the influences of biological sex in both normal brain development and pathology.

Trans-complementation by the RecB nuclease domain of RecBCD enzyme reveals new insight into RecA loading upon χ recognition.

The loading of RecA onto ssDNA by RecBCD is an essential step of RecBCD-mediated homologous recombination. RecBCD facilitates RecA-loading onto ssDNA in a χ-dependent manner via its RecB nuclease domain (RecBn). Before recognition of χ, RecBn is sequestered through interactions with RecBCD. It was proposed that upon χ-recognition, RecBn undocks, allowing RecBn to swing out via a contiguous 70 amino acid linker to reveal the RecA-loading surface, and then recruit and load RecA onto ssDNA. We tested this hypothesis by examining the interactions between RecBn (RecB928-1180) and truncated RecBCD (RecB1-927CD) lacking the nuclease domain. The reconstituted complex of RecB1-927CD and RecBn is functional in vitro and in vivo. Our results indicate that despite being covalently severed from RecB1-927CD, RecBn can still load RecA onto ssDNA, establishing that RecBn does not function while only remaining tethered to the RecBCD complex via the linker. Instead, RecBCD undergoes a χ-induced intramolecular rearrangement to reveal the RecA-loading surface.

Adverse effects of sodium-glucose cotransporter-2 inhibitors in patients with heart failure: a systematic review and meta-analysis.

Sodium-glucose cotransoporter-2 inhibitors (SGLT-2Is) improve prognosis in heart failure (HF) patients both with reduced ejection fraction (HFrEF) and preserved ejection fraction (HFpEF). However, these drugs can have some side effects. To estimate the relative risk of side effects in HF patients treated with SGLT-2Is irrespective from left ventricular EF and setting (chronic and non-chronic HF). Five randomized controlled trials (RCTs) enrolling patients with HFrEF, 4 RCTs enrolling non-chronic HF, and 3 RCTs enrolling HFpEF were included. Among side effects, urinary infection, genital infection, acute kidney injury, diabetic ketoacidosis, hypoglycemia, hyperkalemia, hypokalemia, bone fractures, and amputations were considered in the analysis. Overall, 24,055 patients were included in the analysis: 9020 (38%) patients with HFrEF, 12,562 (52%) with HFpEF, and 2473 (10%) with non-chronic HF. There were no differences between SGLT-2Is and placebo in the risk to develop diabetic ketoacidosis, hypoglycemia, hyperkalemia, hypokalemia, bone fractures, and amputations. HFrEF patients treated with SGLT-2Is had a significant reduction of acute kidney injury (RR = 0.54 (95% CI 0.33-0.87), p = 0.011), whereas no differences have been reported in the HFpEF group (RR = 0.94 (95% CI 0.83-1.07), p = 0.348) and non-chronic HF setting (RR = 0.79 (95% CI 0.55-1.15), p = 0.214). A higher risk to develop genital infection (overall 2.57 (95% CI 1.82-3.63), p < 0.001) was found among patients treated with SGLT-2Is irrespective from EF (HFrEF: RR = 1.96 (95% CI 1.17-3.29), p = 0.011; HFpEF: RR = 3.04 (95% CI 1.88-4.90), p < 0.001). The risk to develop urinary infections was increased among SGLT-2I users in the overall population (RR = 1.13 (95% CI 1.00-1.28), p = 0.046) and in the HFpEF setting (RR = 1.19 (95% CI 1.02-1.38), p = 0.029), whereas no differences have been reported in HFrEF (RR = 1.05 (95% CI 0.81-1.36), p = 0.725) and in non-chronic HF setting (RR = 1.04 (95% CI 0.75-1.46), p = 0.806). SGLT-2Is increase the risk of urinary and genital infections in HF patients. In HFpEF patients, the treatment increases the risk of urinary infections compared to placebo, whereas SGLT-2Is reduce the risk of acute kidney disease in patients with HFrEF.

Scalable stable comb-to-tone integrated RF photonic drive for superconducting qubits.

The recent advent of quantum computing has the potential to overhaul security, communications, and scientific modeling. Superconducting qubits are a leading platform that is advancing noise-tolerant intermediate-scale quantum processors. The implementation requires scaling to large numbers of superconducting qubits, circuit depths, and gate speeds, wherein high-purity RF signal generation and effective cabling transport are desirable. Fiber photonic-enhanced RF signal generation has demonstrated the principle of addressing both signal generation and transport requirements, supporting intermediate qubit numbers and robust packaging efforts; however, fiber-based approaches to RF signal distribution are often bounded by their phase instability. Here, we present a silicon photonic integrated circuit-based version of a photonic-enhanced RF signal generator that demonstrates the requisite stability, as well as a path towards the necessary signal fidelity.

Evaluation of high dose N- Acetylcysteine on airway inflammation and quality of life outcomes in adults with bronchiectasis: A randomised placebo-controlled pilot study.

BACKGROUND: High dose N acetylcysteine (NAC), a mucolytic, anti-inflammatory and antioxidant agent has been shown to significantly reduce exacerbations, and improve quality of life in placebo controlled, double blind randomised (RCT) studies in patients with COPD, and in an open, randomised study in bronchiectasis. In this pilot, randomised, double-blind, placebo-controlled study, we wished to investigate the feasibility of a larger clinical trial, and the anti-inflammatory and clinical benefits of high dose NAC in bronchiectasis. AIMS: Primary outcome: to assess the efficacy of NAC 2400 mg/day at 6 weeks on sputum neutrophil elastase (NE), a surrogate marker for exacerbations. Secondary aims included assessing the efficacy of NAC on sputum MUC5B, IL-8, lung function, quality of life, and adverse effects. METHODS: Participants were randomised to receive 2400 mg or placebo for 6 weeks. They underwent 3 visits: at baseline, week 3 and week 6 where clinical and sputum measurements were assessed. RESULTS: The study was stopped early due to the COVID pandemic. In total 24/30 patients were recruited, of which 17 completed all aspects of the study. Given this, a per protocol analysis was undertaken: NAC (n = 9) vs placebo (n = 8): mean age 72 vs 62 years; male gender: 44% vs 50%; baseline median FEV11.56 L (mean 71.5 % predicted) vs 2.29L (mean 82.2% predicted). At 6 weeks, sputum NE fell by 47% in the NAC group relative to placebo (mean fold difference (95%CI: 0.53 (0.12,2.42); MUC5B increased by 48% with NAC compared with placebo. Lung function, FVC improved significantly with NAC compared with placebo at 6 weeks (mean fold difference (95%CI): 1.10 (1.00, 1.20), p = 0.045. Bronchiectasis Quality of life measures within the respiratory and social functioning domains demonstrated clinically meaningful improvements, with social functioning reaching statistical significance. Adverse effects were similar in both groups. CONCLUSION: High dose NAC exhibits anti-inflammatory benefits, and improvements in aspects of quality of life and lung function measures. It is safe and well tolerated. Further larger placebo controlled RCT's are now warranted examining its role in reducing exacerbations.

Ticagrelor was associated with lower fracture risk than clopidogrel in the dual anti-platelet regimen among patients with acute coronary syndrome treated with percutaneous coronary intervention.

PURPOSE: Patients with coronary artery disease have increased fracture risks. P2Y12 inhibitors may impact fracture risks. We compared the fracture risks associated with ticagrelor and clopidogrel in dual anti-platelet therapy (DAPT). METHODS: We identified all adults who underwent first-ever percutaneous coronary intervention (PCI) for acute coronary syndrome (ACS) between 2010 and 2017 from a territory-wide PCI registry in Hong Kong. Following 1:1 propensity-score matching for baseline characteristics, patients were followed up till event occurrence, death, or 30 June 2022. Outcomes of interest were major osteoporotic fractures (MOF) identified by validated ICD-9-CM codes. Cox proportional hazards regression was used to compute the hazard ratio (HR) for MOF associated with ticagrelor versus clopidogrel use. RESULTS: 3018 ticagrelor users and 3018 clopidogrel users were identified after propensity-score matching (mean age: 61.4 years; 84.1% men). Upon median follow-up of 6.5 years, 59 ticagrelor users and 119 clopidogrel users sustained MOF (annualized fracture risks: 0.34% and 0.56%, respectively). Ticagrelor use was associated with lower risks of MOF (HR 0.60, 95%CI 0.44-0.83; p = 0.002). Consistent HRs were observed for fractures over vertebrae, hip and upper limbs. Subgroup analyses showed no interaction according to age, sex, presence of diabetes, presence of chronic kidney disease and prior fracture history. CONCLUSION: Among adults who underwent first-ever PCI for ACS, ticagrelor use in the DAPT was associated with a lower risk of MOF compared with clopidogrel. Our results support the use of ticagrelor in the DAPT from the perspective of bone health.

Transient modes for the coupled modified Korteweg-de Vries equations with negative cubic nonlinearity: Stability and applications of breathers.

Dynamics and properties of breathers for the modified Korteweg-de Vries equations with negative cubic nonlinearities are studied. While breathers and rogue waves are absent in a single component waveguide for the negative nonlinearity case, coupling can induce regimes of modulation instabilities. Such instabilities are correlated with the existence of rogue waves and breathers. Similar scenarios have been demonstrated previously for coupled systems of nonlinear Schrödinger and Hirota equations. Both real- and complex-valued modified Korteweg-de Vries equations will be treated, which are applicable to stratified fluids and optical waveguides, respectively. One special family of breathers for coupled, complex-valued equations is derived analytically. Robustness and stability of breathers are studied computationally. Knowledge of the growth rates of modulation instability of plane waves provides an instructive prelude on the robustness of breathers to deterministic perturbations. A theoretical formulation of the linear instability of breathers will involve differential equations with periodic coefficient, i.e., a Floquet analysis. Breathers associated with larger eigenvalues of the monodromy matrix tend to suffer greater instability and increased tendency of distortion. Predictions based on modulation instability and Floquet analysis show excellent agreements. The same trend is obtained for simulations conducted with random noise disturbances. Linear approaches like modulation instabilities and Floquet analysis, thus, generate a very illuminating picture of the nonlinear dynamics.

Inconsistent Classification of "Outpatient" Surgeries Leads to Different Outcomes Following Total Hip Arthroplasty in Medicare Beneficiaries: A Critical Analysis.

BACKGROUND: With rising utilization of outpatient total hip arthroplasty (THA) in older patients including Medicare beneficiaries, the objective was to compare differences in definition including (1) patient demographics; (2) lengths of stay (LOS); and (3) outcomes of "outpatient" (stated status) versus "same-day discharge" (SDD) (actual LOS = 0 days) utilizing a nationwide database. METHODS: A national database from 2015 to 2019 was queried for Medicare-aged patients undergoing outpatient THA. Total outpatient THAs (N = 6,072) were defined in one of 2 ways: either "outpatient" by the hospital (N = 2,003) or LOS = 0 days (N = 4,069). Demographics, LOS, discharge destinations, and complications were compared between groups. Logistic regression models computed odds ratios (ORs) for factors leading to complications, readmissions, and nonhome discharges. P values < .008 were significant. RESULTS: Women (OR: 1.19, P = .002), diabetes mellitus (OR: 1.31, P = .003), general anesthesia (OR: 1.24, P = .001), and longer operative times (≥95 minutes) (OR: 1.82, P < .001) were associated with 'outpatient' designation versus SDD. Within the hospital-defined 'outpatient' cohort, 49.1% (983 of 2,003) were discharged the same day (LOS = 0 days), and 21.8% had LOS 2 or more days. The hospital-defined 'outpatient' cohort had greater odds of nonhome discharges (6.3 versus 2.8%; OR: 1.88, P < .001) compared to SDD surgeries. The incidence was higher for any complication among hospital-defined 'outpatient' designated patients compared to SDD (5.5 versus 3.9%, P = .007). CONCLUSIONS: Outpatient surgeries may be misleading and often do not correlate with SDD, as over 20% remain in the hospital 2 or more days. Investigators should quantitatively define the "outpatient" status by actual LOS to allow standardization and results comparison. LEVEL OF EVIDENCE: III.

Changes in cardiovascular disease risk predicted by the Framingham risk model in the Hong Kong population between 2003-2005 and 2014-2015: data from Population Health Surveys.

INTRODUCTION: The Framingham risk model estimates a person's 10-year cardiovascular disease (CVD) risk. This study used this model to calculate the changes in sex- and age-specific CVD risks in the Hong Kong Population Health Survey (PHS) 2014/15 compared with two previous surveys conducted during 2003 and 2005, namely, PHS 2003/2004 and Heart Health Survey (HHS) 2004/2005. METHODS: This study included individuals aged 30 to 74 years from PHS 2014/15 (n=1662; n=4 445 868 after population weighting) and PHS 2003/2004 and HHS 2004/2005 (n=818; n=3 495 074 after population weighting) with complete data for calculating the risk of CVD predicted by the Framingham model. Sex-specific CVD risks were calculated based on age, total cholesterol and high-density lipoprotein cholesterol levels, mean systolic blood pressure, smoking habit, diabetic status, and hypertension treatment. Mean sex- and age-specific CVD risks were calculated; differences in CVD risk between the two surveys were compared by independent t tests. RESULTS: The difference in 10-year CVD risk from 2003-2005 to 2014-2015 was not statistically significant (10.2% vs 10.6%; P=0.29). After age standardisation according to World Health Organization world standard population data, a small decrease in CVD risk was observed, from 9.4% in 2003-2005 to 8.8% in 2014-2015. Analysis according to age-group showed that more participants aged 65 to 74 years were considered high risk in 2003 to 2005 (2003-2005: 66.8% vs 2014-2015: 53.1%; P=0.028). This difference may be due to the decrease in smokers among men (2003-2005: 30.5% vs 2014-2015: 24.0%; P<0.001). CONCLUSION: From 2003-2005 to 2014-2015, there was a small decrease in age-standardised 10-year CVD risk. A holistic public health approach simultaneously targeting multiple risk factors is needed to achieve greater decreases in CVD risk.

Detection of significant liver fibrosis in Chinese psoriasis patients receiving methotrexate: a comparison between transient elastography and liver histology.

INTRODUCTION: Methotrexate (MTX) is effective for treating psoriasis and psoriatic arthritis, but its potential hepatoxicity remains a concern. Liver biopsy, the gold standard for detecting MTX-induced liver injury, is invasive and carries considerable risk. Transient elastography (TE) offers a non-invasive alternative for detecting advanced liver fibrosis. This study investigated the performance of TE in detecting MTX-induced liver fibrosis among Chinese psoriasis patients, compared with liver biopsy. METHODS: This study included adult patients with clinical psoriasis. Liver stiffness measurement using TE was performed in patients receiving MTX. Exclusion criteria were known liver cirrhosis, positive viral hepatitis carrier status, or conditions influencing TE performance. Liver biopsy was performed when liver stiffness was ≥7.1 kilopascals (kPa) or when the total cumulative dose (TCD) of MTX was ≥3.5 g. RESULTS: A total of 228 patients were screened; among 34 patients who met the inclusion criteria, nine (26.5%) had significant liver fibrosis (Roenigk grade ≥3a). The area under the receiver operating characteristic curve was 0.76 (95% confidence interval=0.59-0.93; P=0.021), indicating that TE had satisfactory performance in detecting liver fibrosis. A cut-off value of 7.1 kPa of liver stiffness yielded 100% sensitivity and 68% specificity. Liver fibrosis was not correlated with the TCD of MTX or the duration of MTX use; it was significantly correlated with obesity and diabetes status (body mass index ≥30 kg/m2, waist circumference ≥138 cm, and glycated haemoglobin level ≥7.8%). CONCLUSION: Transient elastography is reliable and superior to the TCD for detecting liver fibrosis in Chinese psoriasis patients receiving MTX. Liver biopsy should be reserved for high-risk patients or patients with liver stiffness ≥11.7 kPa on TE.

High-dose pulse methylprednisolone vs. dexamethasone standard therapy for severe and critical COVID-19 pneumonia: Efficacy assessment in a retrospective single-centre experience from Malaysia.

INTRODUCTION: The use of dexamethasone (DXM) has been associated with decreased mortality in the patients with hypoxemia during the coronavirus disease-2019 (COVID-19) pandemic, while the outcomes with methylprednisolone (MTP) have been mixed. This real-life study aimed to evaluate the outcomes of patients with severe respiratory failure due to COVID-19 who were treated with high doses of MTP. MATERIALS AND METHODS: This retrospective cohort study enrolled hospitalised patients between May 2021 and August 2021, aged 18 years and above, with severe respiratory failure defined by a ratio of oxygen saturation to fraction of inspired oxygen (SF ratio) of less than 235. The treatment protocol involved administering high-dose MTP for 3 days, followed by DXM, and the outcomes were compared with those of patients who received DXM alone (total treatment duration of 10 days for both groups). RESULTS: A total of 99 patients were enrolled, with 79 (79.8%) receiving pulse MTP therapy and 20 (20.2%) being treated with DXM only. The SF ratio significantly improved from a mean of 144.49 (±45.16) at baseline to 208 (±85.19) at 72 hours (p < 0.05), with a mean difference of 63.51 (p < 0.001) in patients who received ≤750 mg of MTP. Additionally, in patients who received >750 mg of MTP, the SF ratio improved from a baseline mean of 130.39 (±34.53) to 208.44 (±86.61) at 72 hours (p < 0.05), with a mean difference of 78.05 (p = 0.001). In contrast, patients who received DXM only demonstrated an SF ratio of 132.85 (±44.1) at baseline, which changed minimally to 133.35 (±44.4) at 72 hours (p = 0.33), with a mean difference of 0.50 (p = 0.972). The incidence of nosocomial infection was higher in the MTP group compared with the DXM group (40.5% vs. 35%, p = 0.653), with a relative risk of 1.16 (95% CI: 0.60-2.23). CONCLUSION: MTP did not demonstrate a significant reduction in intubation or intensive care unit admissions. Although a high dose of MTP improved gas exchange in patients with severe and critical COVID-19, it did not provide an overall mortality benefit compared to standard treatment.

Sacubitril/valsartan and arrhythmic burden in patients with heart failure and reduced ejection fraction: a systematic review and meta-analysis.

The aim of this study was to assess whether angiotensin receptor/neprilysin inhibitor (ARNI) decreases ventricular arrhythmic burden compared to angiotensin-converting enzyme inhibitors or angiotensin receptor antagonist (ACE-I/ARB) treatment in chronic heart failure with reduced ejection fraction (HFrEF) patients. Further, we assessed if ARNI influenced the percentage of biventricular pacing. A systematic review of studies (both RCTs and observational studies) including HFrEF patients and those receiving ARNI after ACE-I/ARB treatment was conducted using Medline and Embase up to February 2023. Initial search found 617 articles. After duplicate removal and text check, 1 RCT and 3 non-RCTs with a total of 8837 patients were included in the final analysis. ARNI was associated with a significative reduction of ventricular arrhythmias both in RCT (RR 0.78 (95% CI 0.63-0.96); p = 0.02) and observational studies (RR 0.62; 95% CI 0.53-0.72; p < 0.001). Furthermore, in non-RCTs, ARNI also reduced sustained (RR 0.36 (95% CI 0.2-0.63); p < 0.001), non-sustained VT (RR 0.67 (95% CI 0.57-0.80; p = 0.007), ICD shock (RR 0.24 (95% CI 0.12-0.48; p < 0.001), and increased biventricular pacing (2.96% (95% CI 2.25-3.67), p < 0.001). In patients with chronic HFrEF, switching from ACE-I/ARB to ARNI treatment was associated with a consistent reduction of ventricular arrhythmic burden. This association could be related to a direct pharmacological effect of ARNI on cardiac remodeling.Trial registration: CRD42021257977.

Preclinical evaluation of the VEGF/Ang2 bispecific nanobody BI 836880 in nasopharyngeal carcinoma models.

Epstein-Barr virus (EBV)-associated nasopharyngeal carcinoma (NPC) is endemic to parts of Asia and overexpression of vascular endothelial growth factor (VEGF) and hypoxia-inducible factor-1α are common in NPC. Anti-vascular agents have known clinical activity in patients with recurrent/ metastatic NPC and in this study, we investigated the anti-tumor effect of BI 836880, a humanized bispecific nanobody against VEGF and angiopoietin-2 (Ang2), in preclinical models of EBV-positive and EBV-negative NPC. The efficacy of BI 836880 was also compared with bevacizumab, a recombinant humanized monoclonal antibody against VEGF. We found that BI 836880 could exert growth-inhibitory effect on endothelial cells (HUVEC-C) and the EBV-negative NPC cell line (HK1), but to a lesser extent in the EBV-positive NPC cell lines, C17C and C666-1. In patients-derived xenograft (PDX) models of NPC - Xeno-2117 and Xeno-666, BI 836880 could suppress tumor growth and Ki67, as well as induce tumor necrosis and reduce microvessel density. Moreover, treatment with BI 836880 increased the level of macrophage infiltration in both PDX tumor models of NPC, suggesting that BI 836880 may exert immunomodulatory effect on the NPC immune microenvironment. When compared with bevacizumab, BI 836880 appeared to show at least comparable activity as bevacizumab in terms of its anti-proliferative and anti-angiogenic effects. This study showed that BI 836880 has anti-proliferative, anti-angiogenic and possibly immunomodulatory effect in clinical models of NPC, therefore the dual targeting of VEGF and Ang2 signaling in NPC should be further investigated.

Forest productivity recovery or collapse? Model-data integration insights on drought-induced tipping points.

More frequent and severe droughts are driving increased forest mortality around the globe. We urgently need to describe and predict how drought affects forest carbon cycling and identify thresholds of environmental stress that trigger ecosystem collapse. Quantifying the effects of drought at an ecosystem level is complex because dynamic climate-plant relationships can cause rapid and/or prolonged shifts in carbon balance. We employ the CARbon DAta MOdel fraMework (CARDAMOM) to investigate legacy effects of drought on forest carbon pools and fluxes. Our Bayesian model-data fusion approach uses tower observed meteorological forcing and carbon fluxes to determine the response and sensitivity of aboveground and belowground ecological processes associated with the 2012-2015 California drought. Our study area is a mid-montane mixed conifer forest in the Southern Sierras. CARDAMOM constrained with gross primary productivity (GPP) estimates covering 2011-2017 show a ~75% reduction in GPP, compared to negligible GPP change when constrained with 2011 only. Precipitation across 2012-2015 was 45% (474 mm) lower than the historical average and drove a cascading depletion in soil moisture and carbon pools (foliar, labile, roots, and litter). Adding 157 mm during an especially stressful year (2014, annual rainfall = 293 mm) led to a smaller depletion of water and carbon pools, steering the ecosystem away from a state of GPP tipping-point collapse to recovery. We present novel process-driven insights that demonstrate the sensitivity of GPP collapse to ecosystem foliar carbon and soil moisture states-showing that the full extent of GPP response takes several years to arise. Thus, long-term changes in soil moisture and carbon pools can provide a mechanistic link between drought and forest mortality. Our study provides an example for how key precipitation threshold ranges can influence forest productivity, making them useful for monitoring and predicting forest mortality events.

Transient deformation and swelling of paper by aqueous co-solvent solutions.

Inkjet printing inks frequently contain polar liquids of low volatility such as glycerol or poly(ethylene glycols) in addition to the main solvent water. The deposition of these liquids on paper sheets induces swelling of the cellulose fibers, which leads to an overall, anisotropic deformation of the sheet. We characterized the corresponding strain components by means of a grid projection method and white light interferometry. For pure water, most of the hydroexpansion strain vanishes again after drying is complete. However, for aqueous solutions of non-volatile co-solvents, a large fraction of the deformation persists after the water has evaporated. Because swelling occurs only after liquid enters the cellulose fibers, monitoring the dynamics of expansion provides insight into the pore-fiber distribution of co-solvents. The corresponding timescales of pore-fiber transport strongly depend on the co-solvent concentration, as a sufficient quantity of water is needed to plasticize the fiber walls.

Expedient synthesis of imino-C-nucleoside fleximers featuring a one-pot procedure to prepare aryl triazoles.

Nucleoside analogues such as the antiviral agents galidesivir and ribavirin are of synthetic interest. This work reports a "one-pot" preparation of similar fleximers using a bifunctional copper catalyst that generates the aryl azide in situ, which is captured by a terminal alkyne to effect triazole formation.

High-volume patient-controlled epidural vs. programmed intermittent epidural bolus for labour analgesia: a randomised controlled study.

The aim of neuraxial analgesia is to achieve excellent pain relief with the fewest adverse effects. The most recently introduced technique for epidural analgesia maintenance is the programmed intermittent epidural bolus. In a recent study, we compared this with patient-controlled epidural analgesia without a background infusion and found that a programmed intermittent epidural bolus was associated with less breakthrough pain, lower pain scores, higher local anaesthetic consumption and comparable motor block. However, we had compared 10 ml programmed intermittent epidural boluses with 5 ml patient-controlled epidural analgesia boluses. To overcome this potential limitation, we designed a randomised, multicentre non-inferiority trial using 10 ml boluses in each group. The primary outcome was the incidence of breakthrough pain and total analgesic intake. Secondary outcomes included motor block; pain scores; patient satisfaction; and obstetric and neonatal outcomes. The trial was considered positive if two endpoints were met: non-inferiority of patient-controlled epidural analgesia with respect to breakthrough pain; and superiority of patient-controlled epidural analgesia with respect to local anaesthetic consumption. A total of 360 nulliparous women were allocated randomly to patient-controlled epidural analgesia-only or programmed intermittent epidural bolus groups. The patient-controlled group received 10 ml boluses of ropivacaine 0.12% with sufentanil 0.75 µg.ml-1 ; the programmed intermittent group received 10 ml boluses supplemented by 5 ml patient-controlled boluses. The lockout period was 30 min in each group and the maximum allowed hourly local anaesthetic/opioid consumption was identical between the groups. Breakthrough pain was similar between groups (11.2% patient controlled vs. 10.8% programmed intermittent, p = 0.003 for non-inferiority). Total ropivacaine consumption was lower in the PCEA-group (mean difference 15.3 mg, p < 0.001). Motor block, patient satisfaction scores and maternal and neonatal outcomes were similar across both groups. In conclusion, patient-controlled epidural analgesia is non-inferior to programmed intermittent epidural bolus if equal volumes of patient-controlled epidural analgesia are used to maintain labour analgesia and superior with respect to local anaesthetic consumption.

The impact of a complex school nutrition intervention on double burden of malnutrition among Thai primary school children: a 2-year quasi-experiment.

OBJECTIVE: This study assessed the impacts of the Dekthai Kamsai programme on overweight/obesity, underweight and stunting among male and female primary school students. STUDY DESIGN: A quasi-experiment was conducted in 16 intervention and 19 control schools across Thailand in 2018 and 2019. In total, 896 treated and 1779 control students from grades 1 to 3 were recruited. In intervention schools, a set of multifaceted intervention components were added into school routine practices. Anthropometric outcomes were measured at baseline and at the beginning and end of every school term. METHODS: Propensity score matching with linear and Poisson difference-in-difference analyses were used to adjust for the non-randomisation and to analyse the intervention's effects over time. RESULTS: Compared with controls, the increases in mean BMI-for-age Z-score (BAZ) and the incidence rate of overweight/obesity were lower in the intervention schools at the 3rd, 4th and 8th measurements and the 3rd measurement, respectively. The decrease in mean height-for-age Z-score (HAZ) was lower at the 4th measurement. The decrease in the incidence rate of wasting was lower at the 5th, 7th and 8th measurements. The favourable impacts on BAZ and HAZ were found in both sexes, while the favourable impact on overweight/obesity and unfavourable impact on wasting were found in girls. CONCLUSIONS: This intervention might be effective in reducing BAZ, overweight/obesity, poor height gain, but not wasting. These findings highlight the benefits of a multifaceted school nutrition intervention and a need to incorporate tailor-made interventions for wasting to comprehensively address the double burden of malnutrition.

Cutaneous manifestations, viral load, and prognosis among hospitalised patients with COVID-19: a cohort study.

INTRODUCTION: Various cutaneous manifestations have been reported as symptoms of coronavirus disease 2019 (COVID-19), which may facilitate early clinical diagnosis and management. This study explored the incidence of cutaneous manifestations among hospitalised patients with COVID-19 and investigated its relationships with viral load, co-morbidities, and outcomes. METHODS: This retrospective study included adult patients admitted to a tertiary hospital for COVID-19 from July to September 2020. Clinical information, co-morbidities, viral load (cycle threshold [Ct] value), and outcomes were analysed. RESULTS: In total, 219 patients with confirmed COVID-19 were included. Twenty patients presented with new onset of rash. The incidence of new rash was 9.1% (95% confidence interval=6.25%-14.4%). The most common manifestations were maculopapular exanthem (n=6, 42.9%, median Ct value: 24.8), followed by livedo reticularis (n=4, 28.6%, median Ct value: 21.3), varicella-like lesions (n=2, 14.3%, median Ct value: 19.3), urticaria (n=1, 7.1%, median Ct value: 14.4), and acral chilblain and petechiae (n=1, 7.1%, median Ct value: 33.1). The median Ct values for patients with and without rash were 22.9 and 24.1, respectively (P=0.58). There were no significant differences in mortality or hospital stay between patients with and without rash. Patients with rash were more likely to display fever on admission (P<0.01). Regardless of cutaneous manifestations, patients with older age, hypertension, and chronic kidney disease stage ≥3 had significantly higher viral load and mortality (P<0.05). CONCLUSION: This study revealed no associations between cutaneous manifestation and viral load or clinical outcomes. Older patients with multiple co-morbidities have risks of high viral load and mortality; they should be closely monitored.

Thermal Disorder in Finite-Length Carbon Nanowire.

Enhancement in chemisorption is one of the active research areas in carbon materials. To remedy the thermally degraded chemisorption occurring at high temperatures, we report a comprehensive study of kink structures in free-standing monoatomic carbon nanowires upon heating. Our Monte Carlo simulation considers multi-monoatomic carbon chains laterally interacting by van der Waals forces. Our study reveals that carbon nanowires maintain their linearity regardless of chain length at low temperatures, but this is not the case at high temperatures. Disordered kink structure is observed in short carbon chains, especially above the Peierls transition temperature. A severe kink structure may increase the possibility of attaching negatively charged atoms, thereby contributing to the development of next-generation materials for chemisorption at high temperatures. We have also provided an important indication that any physical property of the finite-length carbon chain predicted by ab initio calculation should reconsider the atomic rearrangement due to thermal instability at high temperatures.