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Ropivacaine perineal infiltration for postpartum pain management in episiotomy repair: a double-blind, randomised, placebo-controlled trial. To investigate whether perineal infiltration of ropivacaine after episiotomy would decrease the incidence of postpartum pain compared with placebo. Two-centre, double-blind, randomised, controlled trial. Two French maternity units, October 2017 to April 2020. 272 women undergoing epidural analgesia with vaginal singleton delivery and mediolateral episiotomy at term (≥37 weeks) were randomly allocated perineal infiltration of ropivacaine (n = 135) or placebo (n = 137) in a 1:1 ratio before episiotomy repair. Patients were followed at short term (12, 24, 48 h), mid-term (day 7) and long-term (3 and 6 months). The primary outcome was the rate of perineal pain, defined by a Numerical Pain Rating Scale (NPRS) exceeding 3/10, in the mid-term (day 7) postpartum period. Secondary outcomes were perineal pain (NPRS) and analgesic intake, quality of life (SF-36), postpartum depression (EPDS), pain neuropathic component (DN4) and sexual health (FSFI). Perineal pain occurred to an equal extent in the ropivacaine and placebo groups at day 7 (34.2% versus 30.4%, odds ratio 1.1, 95% confidence interval 0.7-1.8, p = 0.63). Similar results were recorded in the short and long term. High rates of dyspareunia and postpartum depression were documented in both groups. No differences were highlighted between the groups in terms of analgesic intake, adverse events, pain neuropathic component and postpartum quality of life. This study did not demonstrate any benefit of ropivacaine infiltration over placebo.

Electrochemical hydroboration of carbonyl compounds. A green and sustainable electrochemical hydroboration of carbonyl compounds with HBpin has been reported for the first time. Under catalyst-free and additive-free mild reaction conditions the corresponding boronic esters were obtained in excellent yields via the simple electrochemical hydroboration of various aldehydes and ketones with HBpin at room temperature. The scale-up reaction demonstrated potential practical applications. A plausible reaction mechanism was proposed based on the corresponding deuterium-labelling, radical inhibition and cyclic voltammetry experiments.

Constructing multi-enzymatic cascade reactions for selective production of 6-bromoindirubin from tryptophan in Escherichia coli. 6-Bromoindirubin (6BrIR), found in Murex sea snails, is a precursor of indirubin-derivatives anticancer drugs. However, its synthesis remains limited due to uncharacterized biosynthetic pathways and difficulties in site-specific bromination and oxidation at the indole ring. Here, we present an efficient 6BrIR production strategy in Escherichia coli by using four enzymes, that is, tryptophan 6-halogenase fused with flavin reductase Fre (Fre-L3-SttH), tryptophanase (TnaA), toluene 4-monooxygenase (PmT4MO), and flavin-containing monooxygenase (MaFMO). Although most indole oxygenases preferentially oxygenate the electronically active C3 position of indole, PmT4MO was newly characterized to perform C2 oxygenation of 6-bromoindole with 45% yield to produce 6-bromo-2-oxindole. In addition, 6BrIR was selectively generated without indigo and indirubin byproducts by controlling the reducing power of cysteine and oxygen supply during the MaFMO reaction. These approaches led to 34.1 mg/L 6BrIR productions, making it possible to produce the critical precursor of the anticancer drugs only from natural ingredients such as tryptophan, NaBr, and oxygen.

High-Throughput Sizing, Counting, and Elemental Analysis of Anisotropic Multimetallic Nanoparticles with Single-Particle Inductively Coupled Plasma Mass Spectrometry. Nanoparticles (NPs) have wide applications in physical and chemical processes, and their individual properties (e.g., shape, size, and composition) and ensemble properties (e.g., distribution and homogeneity) can significantly affect the performance. However, the extrapolation of information from a single particle to the ensemble remains a challenge due to the lack of suitable techniques. Herein, we report a high-throughput single-particle inductively coupled plasma mass spectrometry (SP-ICP-MS)-based protocol to simultaneously determine the size, count, and elemental makeup of several thousands of (an)isotropic NPs independent of composition, size, shape, and dispersing medium with atomistic precision in a matter of minutes. By introducing highly diluted nebulized aqueous dispersions of NPs directly into the plasma torch of an ICP-MS instrument, individual NPs are atomized and ionized, resulting in ion plumes that can be registered by the mass analyzer. Our proposed protocol includes a phase transfer step for NPs synthesized in organic media, which are otherwise incompatible with ICP-MS instruments, and a modeling tool that extends the measurement of particle morphologies beyond spherical to include cubes, truncated octahedra, and tetrahedra, exemplified by anisotropic Cu NPs. Finally, we demonstrate the versatility of our method by studying the doping of bulk-dilute (<1 at. %) CuAg nanosurface alloys as well as the ease with which ensemble composition distributions of multimetallic NPs (i.e., CuPd and CuPdAg) can be obtained providing different insights in the chemistry of nanomaterials. We believe our combined protocol could deepen the understanding of macroscopic phenomena involving nanoscale structures by bringing about a statistics renaissance in research areas including, among others, materials science, materials chemistry, (nano)physics, (nano)photonics, catalysis, and electrochemistry.

Two new glycosides from Stachys geobombycis C.Y.Wu. Two new compounds geobomlin A (1) and geobomlin B (2) were isolated from the roots of Stachys geobombycis C. Y. Wu. Structural determinations were established principally by two-dimensional NMR and MS data analyses. Geobomlin B showed moderate inhibitory activity against α-glucosidase with IC50 = 248.77 μM. We have also determined the mechanism by which geobomlin B elicit its inhibitory effect on α-glucosidase, for which we have established a competitive inhibition mode. Docking studies confirmed our results on geobomlin B α-glucosidase inhibitory properties.

Microbial Multitrophic Communities Drive the Variation of Antibiotic Resistome in the Gut of Soil Woodlice (Crustacea: Isopoda). Multitrophic communities inhabit in soil faunal gut, including bacteria, fungi, and protists, which have been considered a hidden reservoir for antibiotic resistance genes (ARGs). However, there is a dearth of research focusing on the relationships between ARGs and multitrophic communities in the gut of soil faunas. Here, we studied the contribution of multitrophic communities to variations of ARGs in the soil woodlouse gut. The results revealed diverse and abundant ARGs in the woodlouse gut. Network analysis further exhibited strong connections between key ecological module members and ARGs, suggesting that multitrophic communities in the keystone ecological cluster may play a pivotal role in the variation of ARGs in the woodlouse gut. Moreover, long-term application of sewage sludge significantly altered the woodlice gut resistome and interkingdom communities. The variation portioning analysis indicated that the fungal community has a greater contribution to variations of ARGs than bacterial and protistan communities in the woodlice gut after long-term application of sewage sludge. Together, our results showed that changes in gut microbiota associated with agricultural practices (e.g., sewage sludge application) can largely alter the gut interkingdom network in ecologically relevant soil animals, with implications for antibiotic resistance, which advances our understanding of the microecological drivers of ARGs in terrestrial ecosystem.

Surface-Sensitive Imaging Analysis of Cell-Microenvironment Interactions by Electrochemiluminescence Microscopy. A complex and heterogeneous cell microenvironment offers not only structural support for cells but also myriad biochemical and biophysical cues. These outside-in signals transmit into cells primarily through integrins, which are the important components of cell-matrix adhesions to direct and maintain cell behaviors and fate. In this work, we report a surface-sensitive imaging methodology for evaluating the difference in cell-matrix adhesions at the single cell level to dissect the impact of the chemical microenvironment on cell behaviors. Cells were cultured on silica nanochannel membrane (SNM) modified indium tin oxide (ITO) electrodes (SNM/ITO) with different terminal surfaces and imaged by electrochemiluminescence microscopy (ECLM). The results show that the surface tethered with Arg-Gly-Asp (RGD) groups can mediate robust cell-microenvironment interaction and those coated with silanol and (3-aminopropyl)triethoxysilane (APTES) groups transmit an intermediate adhesion, while oligo(ethylene glycol) (OEG) coated surface conveys the weakest cell-matrix adhesion. Specific recognition of integrins to different surfaces was further explored in conjunction with selective immunoblocking of different subunits. α6, α5, and α1 integrin subunits were found to recognize SNM, RGD/OEG, and APTES surfaces, respectively. The work provides not only insights into cell-microenvironment interaction but also guideline in the design and development of functional and biomimetic surface materials.

The effectiveness of moral disengagement and social norms as anti-bullying components: A randomized controlled trial. This three-armed randomized controlled trial examined how moral disengagement and social norms account for change in bullying behavior and their potential as targets of anti-bullying components within separate interventions among 1200 French-speaking Belgian elementary students (48% boys, 9-12 year-olds, 57 classes, nine schools) during 2018-2019 (no ethnicity data available). Mediation analysis revealed that students' moral disengagement successfully decreased (β = -.46), which, in turn, reduced both bullying (β = .33) and outsider behaviors (β = .20), and increased defending (β = -.10). Intervening on social norms decreased bullying (β = -.18), but not through the perceived injunctive class norm as intended. Guidelines to open the "black box" of anti-bullying programs and determine the cost-effectiveness ratio of their components are provided.

Addition of grapes to both a standard and a high-fat Western pattern diet modifies hepatic and urinary metabolite profiles in the mouse. The benefits of fruit and vegetable dietary consumption are largely defined in epidemiological terms. Relatively little is known about the discrete effects on metabolic pathways elicited by individual dietary fruits and vegetables. To address this, grape powder was added to both a standard and a high-fat Western pattern diet given to 10-week-old female C57BL/6J mice for a period of 91 days, whereupon 24 h urines were collected and the mice euthanized after a 12 h fast for the collection of liver tissue. Alterations in hepatic and urinary metabolite patterns were determined by gas chromatography-mass spectrometry-based metabolomics. Urinary excretion of the gut microbiota metabolites 4-hydroxyphenylacetic acid, 5-hydroxyindole, glyceric acid, gluconic acid and myo-inositol was attenuated when grape was added to the standard diet but the gut microbiota metabolites gluconic acid, scyllo-inositol, mannitol, xylitol, 5-hydroxyindole and 2-deoxyribonic acid were increased in urine when grape was added to the high-fat diet. Increased hepatic ascorbic acid and 5-oxoproline levels indicated the anti-oxidant effect of grape powder on the liver. Pathway enrichment analysis demonstrated that for both standard and high-fat diets, grape addition significantly upregulated the malate-aspartate shuttle indicating enhanced hepatic utilization of glucose via cytosolic glycolysis for mitochondrial ATP production. It is concluded that a grape diet reprogrammes gut microbiota metabolism, attenuates the hepatic oxidative stress of a high-fat diet and increases the efficiency of glucose utilization by the liver for energy production.

An mHealth-Supported antenatal lifestyle intervention may be associated with improved maternal sleep in pregnancy: Secondary analysis from the PEARS trial. To investigate the effect of an antenatal diet and exercise intervention during pregnancy on sleep duration. As a secondary objective, associations between sleep duration and gestational weight gain (GWG), maternal metabolic parameters and pregnancy outcomes were assessed. Secondary analysis. Large tertiary Maternity Hospital in Dublin, Ireland. 326 women with overweight or obesity who participated in the Pregnancy Exercise And Nutrition Research Study (PEARS) randomised controlled trial between March 2013 and August 2016. Secondary analysis of a randomised trial. Impact of the PEARS intervention on sleep duration, and association of sleep duration and maternal metabolic parameters, and pregnancy outcomes. Participants had a mean age of 32.5 ± 4.5 years and median (interquartile range [IQR]) body mass index of 28.3 (26.6-31.2) kg/m2 . The intervention group had a longer sleep duration in late pregnancy (mean difference 17.1 minutes (95% confidence interval [CI] 0.5-33.7) and a higher proportion achieving optimum sleep duration of 7-9 h (54.3 vs. 42.9%, relative risk [RR] 1.28 (95% CI 1.01-1.62). In late pregnancy, sleep duration of <6 h was associated with lower breastfeeding rates on discharge (RR 0.74, 95% CI 0.57-0.95) and higher triglyceride levels (mean difference 0.24, 95% CI 0.10-0.38). There were no significant associations between sleep and incidence of gestational diabetes mellitus or pre-eclampsia/toxaemia, or other metabolic parameters assessed (insulin, fasting glucose, HOMA-IR). A diet and exercise intervention from early pregnancy may promote longer and optimal sleep duration, with maternal benefits such as lower triglyceride levels and higher breastfeeding rates.

Cellular Calcium Signals in Cancer Chemoprevention and Chemotherapy by Phytochemicals. Identifying novel agents for cancer treatment is critical because of obstacles with anticancer drug resistance and lack of drug effectiveness. Intracellular calcium ion (Ca2+), a common second messenger, regulates various cellular pathophysiological processes including cell proliferation, differentiation and apoptosis. Recent studies have shown that the remodeling of Ca2+ signals is associated with cancer occurrence, progression and metastasis. Ca2+ channels, transporter and pumps regulate calcium movement, and alteration of Ca2+ signal component expression/activity is associated with numerous cancer cell activities. Therefore, targeting Ca2+ signals is an attractive research focus in cancer treatment. Phytochemicals, secondary metabolites in plants, exhibit multifaceted effective anticancer activities in various cancers. Although the mechanisms of the anticancer effects of phytochemicals remain unclarified, studies have indicated that many phytochemicals inhibit cancer progression through modulating calcium signals. In this review, we summarize the phytochemicals with demonstrated anticancer effects through their influence on calcium signaling, which may provide new ideas and directions in cancer research.

Helicobacter Pylori Related Gastric Cancer Screening and Cost-Effectiveness Analysis: A Hospital-Based Cross-Sectional Study (SIGES). To evaluate the effectiveness of Helicobacter pylori (Hp) related gastric cancer screening (Hp-GCS) and cost-effectiveness of protocol candidates in a hospital-based cross-sectional study. A total of 163 gastric cancer patients in West China Hospital were retrospectively collected according to ICD-10 code and histologic proof between April 1, 2013 and March 31, 2014, and 15,599 cancer-free controls were simultaneously collected from the health checkup registry. Hp infection was examined by urea breath test (UBT). The prevalence of Hp infection was compared between patients and controls. The diagnostic performance of UBT-based predictive index was tested in both training and validation settings. Cost-effectiveness analysis was conducted to assess candidates of Hp-GCS protocols. The prevalence of Hp infection was 55.8% and 41.2% in gastric cancers and controls, respectively (p < 0.001). UBT-based model showed moderate diagnostic strength in Hp-GCS (AUC = 0.78, 95% CI 0.74-0.82), better than UBT alone (p < 0.001). The sensitivity and specificity of UBT-based index were 80.2% and 61.9% at optimal cutoff in training setting, comparable in validation setting, which sensitivity and specificity were 76.9% and 59.6%. Number needed to screen was decreased along with older age, as well as stronger positivity of UBT. The optimal cost-effective Hp-GCS protocol with detection rate (DR = 77.9%) was endoscopic screening in age 40-59 years and positive UBT, or age ≥60 years without UBT. Incremental analysis suggested a preferable protocol as endoscopic screening in age ≥40 years without UBT (DR = 93.3%). UBT had moderate diagnostic strength in massive gastric cancer screening, and might be cost-effective in middle-aged population (40-59 years). More robust Hp-GCS protocol needs further investigate in test methods and individual biologic features.

Highly Efficient Organic Solar Cells Enabled by the Incorporation of a Sulfonated Graphene Doped PEDOT:PSS Interlayer. An interface modification layer plays an important role in improving the performance of organic solar cells (OSCs). The structure design or doping of electrode interlayer materials can effectively inhibit interfacial carrier recombination and improve ohmic contact between the active layer and the electrodes, which is desirable for realizing high power conversion efficiencies (PCEs). Poly(3,4-ethylenedioxythiophene):poly(styrenesulfonate) (PEDOT:PSS) has been extensively used as a hole-transport layer (HTL) in OSCs. Here, a modification of PEDOT:PSS is proposed using sulfonated graphene (SG) as a secondary dopant for improving the surface morphology and conductivity. The incorporation of the SG-doped PEDOT:PSS as the HTLs in OSCs leads to the increased charge extraction and shows the best PCEs of 17.48% for PM6:Y6 devices and 18.56% for PM6:L8-BO devices. The significant improvement in device performance suggests that SG-PEDOT:PSS is a promising interfacial layer for efficient charge transport and extraction toward high-efficiency OSCs.

Antifreezing, Ionically Conductive, Transparent, and Antidrying Carboxymethyl Chitosan Self-Healing Hydrogels as Multifunctional Sensors. Through a simple strategy of immersion in a mixed solution of water/ethylene glycol (EG)/lithium chloride (LiCl), self-healing carboxymethyl chitosan (CA) hydrogels, that is, CA/N-vinylpyrrolidone-EG-Li+ hydrogels (CEH) with an ultra-low-temperature freezing resistance below -70 °C were fabricated. The introduction of electrolyte ions and small-molecule polyol also made these hydrogels highly conductive (0.8 S m-1) and imparted antidrying property to them, showing stable and reversible sensitivity to finger-wrist bending as well as 150 cycles of stretching. Such hydrogels also presented highly efficient self-healing ability, with a stress-strain healing efficiency of over 90%. Furthermore, the CEH-based sensors maintained a stable sensing performance over a wide range of temperatures below the freezing point (from -10 to -70 °C) and exhibited stable sensitivity to temperatures with fast response and no significant hysteresis. The present work is expected to provide a simple and sustainable route for the preparation of multifunctional antifreezing conductive hydrogels based on CA, leading to a wide range of potential applications in soft sensor devices.

The potential role of Bifidobacterium spp. as a preventive and therapeutic agent in controlling inflammation via affecting inflammatory signalling pathways. Inflammatory bowel disease (IBD) is a chronic inflammatory disease with relapses and periods of remission. Forasmuch as, dysregulation of the immune system is one of the triggers of IBD, taking probiotics as one of the immunomodulators in the gut, could help to control inflammation and IBD via influencing signalling pathways. Here, we aimed to investigate the efficacy of five selected Bifidobacterium strains in modulating JAK/STAT and NF-kB inflammatory signalling pathways via using the in vitro assay. A quantitative real-time polymerase chain reaction assay was used to analyse the expression of JAK/STAT and inflammatory genes followed by potential probiotic treatments before, after and simultaneously with the inflammation induction (sonicated pathogen). The production of IL-6 and IL-1β after probiotic treatment was evaluated. Probiotic treatment resulted in the downregulation of TIRAP, IRAK4, NEMO and RIP genes in the NF-kB pathway, as well as JAK genes compared to sonicate-treated cells. The expression of STAT genes was different after our selected Bifidobacterium strains treatment. The production of IL-6 and IL-1β decreased after probiotic treatment. These strains of Bifidobacterium spp. showed anti-inflammatory effects on HT-29 cells via modulation of JAK/STAT and NF-kB signalling pathways. The use of Bifidobacterium spp. could be considered as a suitable preventive and complementary treatment for patients with inflammatory bowel disease.

Healthcare consumers' and professionals' perceived acceptability of evidence-based interventions for rural transitional care. There is a pressing need for high quality hospital-to-home transitional care in rural communities. Four evidence-based interventions (discharge planning, treatments, warning signs, and physical activity) have the potential to improve rural transitional care. However, there is limited understanding of how the perceptions of healthcare consumers and professionals compare on the acceptability of the interventions. Convergent views on intervention acceptability support implementation, whereas divergent views highlight areas requiring reconciliation prior to implementation. This study compared the acceptability of four evidence-based interventions proposed for rural transitional care, as perceived by healthcare consumers and professionals. A cross-sectional, comparative design was used. The convenience sample included 36 healthcare consumers (20 patients and 16 family caregivers) who had experienced a hospital-to-home transition in the past month and 30 healthcare professionals (29 registered nurses and one nurse practitioner) who provided transitional care in rural Ontario, Canada. Participants were presented with descriptions of the four interventions and completed an established intervention acceptability measure. Presentation of the four intervention descriptions and respective acceptability measures was randomized to control for possible order effects. The perceived overall acceptability of the interventions and their attributes (i.e., effectiveness, appropriateness, risk, and convenience) were compared using independent samples t-tests. Consumer ratings were consistently higher across all four interventions in terms of overall acceptability as well as effectiveness, appropriateness, and convenience (all p's < .01; effect sizes 0.70-1.13). No significant between-group differences in perceived risk were found. Contextual and methodological differences may account for variability in ratings, but further research is needed to explore these propositions. The results support future qualitative inquiry targeting professionals to better understand their perspectives on the effectiveness, appropriateness, and convenience of the four interventions.

Identification of dual-targeted Mycobacterium tuberculosis aminoacyl-tRNA synthetase inhibitors using machine learning. Background: The most serious challenge in the treatment of tuberculosis is the multidrug resistance of Mycobacterium tuberculosis to existing antibiotics. As a strategy to overcome resistance we used a multitarget drug design approach. The purpose of the work was to discover dual-targeted inhibitors of mycobacterial LeuRS and MetRS with machine learning. Methods: The artificial neural networks were built using module nnet from R 3.6.1. The inhibitory activity of compounds toward LeuRS and MetRS was investigated in aminoacylation assays. Results: Using a machine-learning approach, we identified dual-targeted inhibitors of LeuRS and MetRS among 2-(quinolin-2-ylsulfanyl)-acetamide derivatives. The most active compound inhibits MetRS and LeuRS with IC50 values of 33 μm and 23.9 μm, respectively. Conclusion: 2-(Quinolin-2-ylsulfanyl)-acetamide scaffold can be useful for further research.

The first crystal structure of a xylobiose-bound xylobiohydrolase with high functional specificity from the bacterial glycoside hydrolase family 30, subfamily 10. Xylobiose is a prebiotic sugar that has applications in functional foods. This report describes the first X-ray crystallographic structure models of apo and xylobiose-bound forms of a xylobiohydrolase (XBH) from Acetivibrio clariflavus. This xylan-active enzyme, a member of the recently described glycoside hydrolase family 30 (GH30), subfamily 10, phylogenetic clade has been shown to strictly release xylobiose as its primary hydrolysis product. Inspection of the apo structure reveals a glycone region X2 -binding slot. When X2 binds, the non-reducing xylose in the -2 subsite is highly coordinated with numerous hydrogen bond contacts while contacts in the -1 subsite mostly reflect interactions typical for GH30 and enzymes in clan A of the carbohydrate-active enzymes database (CAZy). This structure provides an explanation for the high functional specificity of this new bacterial GH30 XBH subfamily.

Clinician experiences of homework in couples and family therapy: A survey of perceived impact on the working alliance. The process of engaging clients in homework assignments has been studied extensively in research settings, but rarely have the challenges in the implementation of the science been considered in couples and family therapy. A survey was conducted of 226 clinicians regarding (1) their experience of homework adherence (quantity and quality) with couple and family clients, and (2) their experience of the impact of homework non-completion (IHN) on the working alliance. Clinicians working with families reported less overall homework quantity and quality. However, across both couples and family clients, more negative IHN was reported among clinicians experiencing less homework quantity, both in terms of IHN bond (couple ρ = 0.71, p < 0.001; family ρ = 0.78, p < 0.001) and IHN agreement (couples ρ = 0.25, p < 0.001; ρ = 0.19, p = 0.006), and among clinicians with fewer years of clinical experience (r = 0.19, n = 136, p < 0.05). The present findings suggest that, in the context of couples and family therapy, there is a risk of perceived negative IHN on the working alliance. There would be merit to future investigations examining the processes of facilitating homework engagement within the context of a strong working alliance.

Trends in imported malaria during the COVID-19 pandemic, Spain (+Redivi Collaborative Network). The COVID-19 pandemic has caused disruptions in prevention and management strategies for malaria globally. Currently, data analysing trends in travel-related infections during the pandemic years are scarce. The objective of this analysis was to describe the epidemiological and clinical characteristics of patients with imported malaria within the +Redivi network in Spain, focusing on yearly trends from pre-pandemic years to date. Cases recorded in +Redivi from October 2009 to December 2021 were analysed and patients with a diagnosis of malaria (standard diagnostic methods using thick/thin peripheral blood smears, with/without a malaria rapid diagnostic test and/or Plasmodium spp. polymerase chain reaction) were identified. The total number of malaria cases, cases according to type of patient and severe cases, per year, were analysed. In total, 1751 cases of malaria (1751/26 601, 6.6%) were identified. The majority occurred in males (1041, 59.5%), median age was 36.3 (interquartile range: 27-44.7) years and most occurred in visiting friends and relatives (VFR)-immigrants (872, 49.8%). Most infections were acquired in sub-Saharan Africa (1.660, 94.8%) and were due to Plasmodium falciparum (81.3%). There were 64 cases of severe malaria (3.7%) and 4 patients died (0.2% mortality, all in pre-pandemic years). A significant increase in cases of severe malaria was observed during the study period (P < 0.001) (attributable to the increase in 2021). There were 16/93 severe cases in 2021 (17.2%), all due to Plasmodium falciparum, (compared with ≤ 5% in previous years), which mainly occurred in travellers and VFR-immigrants (10/16, 62.5% and 5/16, 31.3%, respectively). After an initial decline associated with travel restrictions due to the ongoing COVID-19 pandemic, an increase in imported malaria and a significant increase in cases of severe malaria was observed. Patients with imported malaria may present and/or be diagnosed late during this public health crisis and health care professionals should be alerted to the recent increase in severe cases.

Histopathological risk factors for malignancy in dermatomyositis. To identify possible histopathological risk factors for malignancy in skin biopsies of dermatomyositis patients. We analysed clinical metadata and studied 30 skin biopsies of 11 patients with and 12 patients without associated malignancy, who were treated in one secondary and one tertiary German medical centre between 2009 and 2022 and fulfilling the EULAR/ACR classification criteria for dermatomyositis. Specimens were categorized by malignancy status and evaluated based on haematoxylin and eosin (H&E), periodic acid Schiff (PAS), Alcian Blue, and anti-CD123 immunohistochemistry stains. After correcting for multiple testing, biopsies of patients with cancer exhibited more severe basement membrane thickening (P < 0.05) and pigment incontinence (P < 0.05) compared to patients without tumour burden. Patients with numerous subepidermal melanophages had a more than 5-times increased odds ratio to suffer from an internal malignancy (odds ratio [OR] 5.3, 95% confidence interval [CI] 1.3-54.2, P < 0.05). Furthermore, specimens of the malignancy group presented a distinct superficial distribution pattern of CD123+ plasmacytoid dendritic cells (PDCs, P < 0.01). Extravascular eosinophils were absent in all cases. Severity of basement membrane thickening, extent of pigment incontinence, and superficial distribution pattern of CD123+ PDCs could serve as useful histopathological indicators of risk for malignancy in dermatomyositis.

Rare vascular involvement in Behçet's disease: Coronary artery pseudoaneurysm. Behçet's disease is a relapsing, inflammatory, multi-systemic disease. Coronary arterial involvement in Behçet's disease is very rare with a prevalence of less than 0.5%. We report the case of a 34-year-old man who presented with a coronary artery pseudoaneurysm associated with Behçet's disease. The patient underwent a successful left internal thoracic artery to left anterior descending artery bypass graft procedure, and remains symptom-free in a 6-month follow up with normal electrocardiogram.

Local wound management: A review of modern techniques and products. Management of wounds is a commonly performed and essential aspect of small animal veterinary medicine. Appropriate wound management is a difficult art to master, due to the inherent complexity of the clinical scenario, as well as the ever-evolving nature of the field with the constant addition of new products and techniques. This article reviews key concepts that may help the practitioner better understand the natural process of wound healing, factors that delay healing and strategies to help improve the local wound environment to make it more conducive to healing during open wound management. The concept of wound bed preparation is defined before common local wound management strategies, such as wound lavage and debridement, are discussed in more detail. Key aspects of the management of biofilms and appropriate use of antimicrobial agents are also reviewed. Finally, the concept of moist wound healing and its impact in modern wound management is explained before a broad variety of types of wound dressings are reviewed, with a particular focus on active dressings.

Development of the Extended Infusion Set and Its Mechanism of Action. Continuous subcutaneous insulin infusion (CSII, or insulin pump) and continuous glucose monitoring (CGM) sensors have been increasingly used and associated with improved glycemic control by people with type 1 diabetes and insulin-requiring type 2 diabetes. Commonly used infusion sets in most CSII systems are limited to a wear time of 3 days. In contradistinction, CGM sensors are currently approved for seven and more days of wear. With the motivation to provide a 7-day infusion set that matches the CGM wear time and to improve patient experience, the recently CE-marked and FDA 510k-cleared Medtronic extended infusion set (EIS) was designed.s The EIS offers enhanced new features that include use for up to 7 days, improved convenience, comfort, and better quality of life for insulin pump users.

resPAINT: Accelerating Volumetric Super-Resolution Localisation Microscopy by Active Control of Probe Emission. Points for accumulation in nanoscale topography (PAINT) allows practically unlimited measurements in localisation microscopy but is limited by background fluorescence at high probe concentrations, especially in volumetric imaging. We present reservoir-PAINT (resPAINT), which combines PAINT and active control of probe photophysics. In resPAINT, an activatable probe "reservoir" accumulates on target, enabling a 50-fold increase in localisation rate versus conventional PAINT, without compromising contrast. By combining resPAINT with large depth-of-field microscopy, we demonstrate super-resolution imaging of entire cell surfaces. We generalise the approach by implementing various switching strategies and 3D imaging techniques. Finally, we use resPAINT with a Fab to image membrane proteins, extending the operating regime of PAINT to include a wider range of biological interactions.

Treatment experiences of male and female youths with eating disorders. The current study was conducted to further understand the experiences of youths with an eating disorder with accessing services and receiving treatment. Participants' perceptions of the role of gender in eating disorder treatment was also assessed. A prospective mixed methods design was used, with the current report focusing on qualitative interviews. Youths who were receiving services in a specialized paediatric eating disorder program completed a semi-structured interview in combination with a visual lifeline upon their discharge. A process of interpretative induction was employed to derive high-level concepts from the interviews. A total of 28 youths (15 males and 13 females) completed an interview. Four high-level concepts were identified: (1) unwanted/non-collaborative support, (2) conflicting views, (3) dynamics in relationships (with sub-concepts relating to peers and health professionals), and (4) changing mindset. Although many participants viewed treatment as universal, a subset of participants noted that treatment was tailored towards females. Youths shared several challenges that they encountered in their journey to accessing specialized eating disorders treatment, including disagreement with their parents/caregivers and health professionals about treatment plans. Interactions with peers and health professionals represented both a facilitator (e.g., feeling supported and inspired by peers) and a challenge (e.g., negative interactions with professionals). Some youths shared concerns about the female-centric nature of treatment. The results of this study highlight the importance of collaborative care for paediatric eating disorders, and consideration for gender inclusivity in eating disorders treatment.

Tuning assembly structures of hard shapes in confinement via interface curvature. Assembly in confinement is a problem of great interest in colloidal structure design, plasmonics, photonics, and industrial packaging. Along with the range of design choices provided by particle shape and attraction or repulsion, confined systems add an additional layer of complexity through the interactions between particles and the container holding them. The range of possible behaviors produced by these systems remains largely unexplored, yet has profound consequences on the resultant assembled structure. Here, we address this problem by exploring how the assembly of hard tetrahedral particles is affected by a spherical container. We simulate particle assemblies in containers holding 4 to 10 000 particles and analyze the range of resultant structures. We find that the presence of a curved wall causes organization into distinct concentric shells in containers holding up to thousands of particles. In addition, we see that wall curvature affects structural motifs in systems as large as 10 000 particles, promoting local environments that maximally conform to the wall and providing a seed for the propagation of these motifs into the interior of the container. Through this work, we show how confining interfaces can be used to promote the assembly of structures markedly distinct from those seen in the more commonly studied bulk systems.

Model for active particles confined in a two-state micropattern. We propose a model, based on active Brownian particles, for the dynamics of cells confined in a two-state micropattern, composed of two rectangular boxes connected by a bridge, and investigate the transition statistics. A transition between boxes occurs when the active particle crosses the center of the bridge, and the time between subsequent transitions is the dwell time. By assuming that the rotational diffusion time τ is a function of the position, some experimental observations are qualitatively recovered as, for example, the shape of the survival function. τ controls the transition from a ballistic regime at short time scales to a diffusive regime at long time scales, with an effective diffusion coefficient proportional to τ. For small values of τ, the dwell time is determined by the characteristic diffusion timescale which is constant for very low values of τ, when the rotational diffusion is much faster than the translational one and decays with τ for intermediate values of τ. For large values of τ, the interaction with the walls dominates and the particle stays mostly at the corners of the boxes increasing the dwell time. We find that there is an optimal τ for which the dwell time is minimal and its value can be tuned by changing the geometry of the pattern.

Modeling and numerical analysis of fractional order hepatitis B virus model with harmonic mean type incidence rate. A mathematical epidemiological model for the transmission of Hepatitis B virus in the frame of fractional derivative with harmonic mean type incidence rate is proposed in this article. The proposed mathematical model is then fictionalized by utilizing the Atangana-Baleanu-Capotu (ABC) operator with vaccination effects. The threshold number R0 is calculated by utilizing the next-generation matrix approach. The existence and uniqueness of solution of the proposed model are proved by utilizing the well-known fixed point theory. For the numerical solution of the proposed model with ABC derivative the well-known Adams-Bashforth-Molton (ABM) method is utilized. Likewise, stability is required in regard of the numerical arrangement. In this manner, Ulam-Hyers stability utilizing nonlinear functional analysis is utilized for the proposed model.

High cysteine concentrations in cell culture media lead to oxidative stress and reduced bioprocess performance of recombinant CHO cells. Cysteine is considered an essential amino acid in the cultivation of Chinese hamster ovary (CHO) cells. An optimized cysteine supply during fed-batch cultivation supports the protein production capacity of recombinant CHO cell lines. However, we observed that CHO production cell lines seeded at low cell densities in chemically defined media enriched with cysteine greater than 2.5 mm resulted in markedly reduced cell growth during passaging, hampering seed train performance and scale-up. To investigate the underlying mechanism, seeding cell densities and initial cysteine concentrations ranging from low to high cysteine concentrations were varied followed by an analysis of cell culture performance. Additionally, cell cycle analysis, intracellular quantification of reactive oxygen species (ROS) as well as transcriptomic analyses by next-generation sequencing were carried out. Our results demonstrate that CHO cells seeded at low cell densities at high initial cysteine concentrations encountered increased oxidative stress leading to a p21-mediated cell cycle arrest in the G1/S phase. The resulting oxidative stress caused redox imbalance in the endoplasmic reticulum and activation of the unfolded protein response as well as the major antioxidant nuclear factor-like 2 response pathways. Potential signature genes related to oxidative stress and the inhibition of the pentose phosphate pathway were identified in the study. Finally, the study presents that seeding cells at a higher concentration counteract oxidative stress in cysteine-enriched cell culture media.

Toward high-performance refractive index sensor using single Au nanoplate-on-mirror nanocavity. Refractive index sensors based on the localized surface plasmon resonance (LSPR) have emerged as powerful tools in various chemosensing and biosensing applications. However, owing to their limited decay length and strong radiation damping, LSPR sensors always suffer from low sensitivity and small figure of merit (FOM). Here, we fabricate a plasmonic nanocavity sensor consisting of a hexagonal Au nanoplate positioned over an ultrasmooth Au film. The strong coupling between the nanoplate and the lower metal film allows for the formation of a plasmonic gap mode that enhances the interaction of the local field with the ambient glycerol solution to increase the sensitivity. Meanwhile, the plasmonic gap mode has a trait of an antiphase charge oscillation in the gap region, imparting a strongly reduced radiative damping and a subsequently promoted FOM. The performance of our proposed refractive index sensor is further boosted by decreasing the gap size of the nanocavity, yielding an outstanding FOM of 11.2 RIU-1 that is the highest yet reported for LSPR sensing in a single nanostructure.

Pathological aspects of cutaneous mast cell tumors with metastases in 49 dogs. Cutaneous mast cell tumor (MCT) is one of the most frequent cutaneous neoplasms of dogs and may vary from well-differentiated to aggressive tumors with metastasis. The authors retrospectively described the gross and histologic aspects of metastatic MCT in 49 dogs. Primary MCT was most commonly identified in the inguinal region (14/35; 40%), and at necropsy multiple, cutaneous nodules were frequently reported (23/49; 47%). All primary MCT were classified as high-grade neoplasms, and metastases involved the lymph nodes (47/49; 96%), spleen (33/49; 67%), liver (29/49; 59%), bone marrow (20/49; 41%), kidneys (16/49; 33%), and heart (14/49; 29%), while the lungs were less commonly affected (9/49; 18%). The main gross findings included lymphadenomegaly in 47 cases; splenomegaly in 28 cases, with splenic nodules in 13 dogs; hepatomegaly in 28 cases, with white pinpoint foci in 9 cases; nodules on the capsular surface of the kidneys in 9 dogs; and epicardial nodules in 6 cases. Histologically, the lymph nodes were largely obliterated by neoplastic mast cells, while in the spleen, neoplastic cells were multifocally scattered (16/33; 48%), arranged in nodules (10/33; 30%), or obliterated the parenchyma (9/33; 27%). In the liver, the neoplastic cells mainly infiltrated the sinusoids (24/29; 83%), but were also arranged in random nodules (10/29; 34%). Interstitial and nodular metastases were observed in the kidneys and the heart. Grossly unapparent metastases were common in the heart (6/14; 43%), kidneys (4/16; 25%), and lungs (6/9). KIT III and KIT II staining patterns were observed in 29 and 20 cases, respectively.

Cross-Cultural Adaptation, Validation, and Reliability of the Persian Version of the Brief Michigan Hand Questionnaire. Brief Michigan Hand Questionnaire (Brief MHQ) is one of the most reliable and sensitive patient-reported outcome measures for hand and wrist disorders worldwide. This study aimed to assess the psychometric properties of the Persian version of the Brief Michigan Hand Questionnaire based on standard guidelines. One hundred two patients with various hand and wrist disorders filled the Persian version of Brief MHQ along with the Quick Disabilities of the Arm, Shoulder, and Hand (QuickDASH) questionnaire and the visual analogue scale (VAS) for pain. Seventy-eight participants returned to complete the Persian Brief MHQ for the second time after 4 days. The analysis showed excellent internal consistency with a Cronbach's alpha ranging from 0.89 to 0.91. The Persian Brief MHQ has an excellent test-retest reliability with a 0.94 intraclass correlation coefficient (ICC). The correlation coefficient of -0.74 between Brief MHQ and the QuickDASH showed a strong correlation and confirmed its validity. The Persian version of the Brief MHQ is a reliable and valid tool to apply to Persian individuals with hand and wrist disorders.

A convenient synthetic route to (2S,4S)-methylproline and its exploration for protein engineering of thioredoxin. 4-Substituted prolines, especially 4-fluoroprolines, have been widely used in protein engineering and design. Here, we report a robust and stereoselective approach for the synthesis of (2S,4S)-methylproline starting from (2S)-pyroglutamic acid. Incorporation studies with both (2S,4R)- and (2S,4S)-methylproline into the Trx1P variant of the model protein thioredoxin of E. coli show that the stereochemistry of the 4-methyl group might be a key determinator for successful incorporation during ribosomal synthesis of this protein.

Role of glycolysis in the development of atherosclerosis. Atherosclerosis is a chronic inflammatory vascular disease associated with endothelial dysfunction, inflammation, and atherosclerotic plaque formation. Glycolysis is a conservative and rigorous biological process that decomposes glucose into pyruvate. Its function is to provide the body with energy and intermediate products required for life activities. However, abnormalities in glycolysis flux during the progression of atherosclerosis accelerate the disease progression. Herein, we review the role of glycolysis in the development of atherosclerosis to provide new ideas for devising novel antiatherosclerosis strategies.

Rapid nutrient depletion to below the physiological range by cancer cells cultured in Plasmax. Mammalian cell culture is a fundamental tool used to study living cells. Presently, the standard protocol for performing cell culture involves the use of commercial media that contain an excess of nutrients. Although this reduces the likelihood of cell starvation, it creates nonphysiologic culture conditions that have been shown to "re-wire" cellular metabolism. Recently, researchers have developed new media like Plasmax, formulated to approximate the nutrient composition of human blood plasma. Although this represents an improvement in cell culture practice, physiologic media may be vulnerable to nutrient depletion. In this study, we directly addressed this concern by measuring the rates of glucose and amino acid depletion from Plasmax in several cancer cell lines (PC-3, LNCaP, MCF-7, and SH-SY5Y) over 48 h. In all cell lines, depletion of glucose from Plasmax was rapid such that, by 48 h, cells were hypoglycemic (<2 mM glucose). Most amino acids were similarly rapidly depleted to subphysiological levels by 48 h. In contrast, glucose and most amino acids remained within the physiological range at 24 h. When the experiment was done at physiological oxygen (5%) versus standard (18%) with LNCaP cells, no effect on glucose or amino acid consumption was observed. Using RNA sequencing, we show that this nutrient depletion is associated with enrichment of starvation responses, apoptotic signaling, and endoplasmic reticulum stress. A shift from glycolytic metabolism to mitochondrial respiration at 5% O2 was also measured using Seahorse analysis. Taken together, these results exemplify the metabolic considerations for Plasmax, highlighting that cell culture in Plasmax requires daily media exchange.

Functional expression of NaV1.7 channels in freshly dispersed mouse bronchial smooth muscle cells. Isolated smooth muscle cells (SMCs) from mouse bronchus were studied using the whole cell patch-clamp technique at ∼21°C. Stepping from -100 mV to -20 mV evoked inward currents of mean amplitude -275 pA. These inactivated (tau = 1.1 ms) and were abolished when external Na+ was substituted with N-Methyl-d-glucamine. In current-voltage protocols, current peaked at -10 mV and reversed between +20 and +30 mV. The V1/2s of activation and inactivation were -25 and -86 mV, respectively. The current was highly sensitive to tetrodotoxin (IC50 = 1.5 nM) and the NaV1.7 subtype-selective blocker, PF-05089771 (IC50 = 8.6 nM), consistent with NaV1.7 as the underlying pore-forming α subunit. Two NaV1.7-selective antibodies caused membrane-delineated staining of isolated SMC, as did a nonselective pan-NaV antibody. RT-PCR, performed on groups of ∼15 isolated SMCs, revealed transcripts for NaV1.7 in 7/8 samples. Veratridine (30 µM), a nonselective NaV channel activator, reduced peak current evoked by depolarization but induced a sustained current of 40 pA. Both effects were reversed by tetrodotoxin (100 nM). In tension experiments, veratridine (10 µM) induced contractions that were entirely blocked by atropine (1 µM). However, in the presence of atropine, veratridine was able to modulate the pattern of activity induced by a combination of U-46619 (a thromboxane A2 mimetic) and PGE2 (prostaglandin E2), by eliminating bursts in favor of sustained phasic contractions. These effects were readily reversed to control-like activity by tetrodotoxin (100 nM). In conclusion, mouse bronchial SMCs functionally express NaV1.7 channels that are capable of modulating contractile activity, at least under experimental conditions.

Dietary fructose as a metabolic risk factor. Over the past decades, the role of the intestinal microbiota in metabolic diseases has come forward. In this regard, both composition and function of our intestinal microbiota is highly variable and influenced by multiple factors, of which diet is one of the major elements. Between 1970 and 1990, diet composition has changed and consumption of dietary sugars has increased, of which fructose intake rose by more than 10-fold. This increased intake of sugars and fructose is considered as one of the major risk factors in the developments of obesity and several metabolic disturbances. In this review, we describe the association of dietary fructose intake with insulin resistance, nonalcoholic fatty liver disease (NAFLD) and lipid metabolism. Moreover, we will focus on the potential causality of this altered gut microbiota using fecal transplantation studies in human metabolic disease and whether fecal microbial transplant can reverse this phenotype.

Zwitterionic/phosphonate copolymer coatings endow excellent antifouling properties and robust re-mineralization ability of dentine substrates. Inhibition of biofilm formation and induction of the re-mineralization of damaged dental tissues are two major strategies to combat dental hypersensitivity (DH). However, single component synthetic materials normally cannot fulfil these two functions during the repairing of damaged dental tissues. Here, we report zwitterionic phosphorylcholine based polymers to be a new type of dual functional coating for the repairing of DH. Zwitterionic/phosphonate copolymers, p(DEMMP-co-MPC), bearing varied zwitterionic contents (95 and 75 mol%) were prepared through conventional radical copolymerization. 1H NMR spectroscopy clearly indicated the precise preparation of the copolymers. The copolymers can be easily coated on dentine substrates based on the high affinity between the phosphonate group and the calcium phosphate minerals of the dentine substrates, as evidenced by XPS and water contact angle measurements. Antifouling evaluations indicated that zwitterionic coating can efficiently inhibit protein adsorption (BSA, egg white, and milk, by 85%) and bacterial adhesion (by 97.1%) on dentine substrates. Furthermore, in vitro and in vivo experiments consistently indicated that the zwitterionic coating could not only induce the robust re-mineralization of dentine surfaces, but also template the extensive re-mineralization of dentine tubules to a similar level of pristine dentine. Both the antifouling properties and the re-mineralization potency are positively correlated with the content of zwitterionic pMPC in the coating copolymer. These findings may provide the zwitterionic phosphorylcholine based materials to be a promising candidate to treat dental hypersensitivity and other related dental diseases.

Computational insights into the inverse electron-demand Diels-Alder reaction of norbornenes with 1,2,4,5-tetrazines: norbornene substituents' effects on the reaction rate. The study of the reaction rates and mechanism of click chemistry reactions still remains an interesting challenge in organic chemistry. In this regard, the inverse electron demand Diels-Alder (IEDDA) reaction represents a promising metal-free alternative with enhanced reaction rates compared to other reactions of the click chemistry toolbox. Among the different types of dienophiles used in the IEDDA reactions, norbornenes have been widely used given their high stability and fast reaction rates. The inverse electron-demand Diels Alder reaction of 3,6-dipyridin-2-yl-1,2,4,5-tetrazine with a series of norbornene derivatives was studied with quantum mechanical calculations at the M06-2X/6-311+G(d,p) level of theory. The theoretical predictions were confirmed with the experimental data and analyzed with the use of the distortion/interaction model. The obtained results will help in obtaining a better understanding of the factors that affect the relative cycloaddition rates of norbornenes with tetrazines, which are crucial for selectively tuning their efficacy.

Relationship of ANGPTL6 With Neonatal Glucose Homeostasis and Fat Mass Is Disrupted in Gestational Diabetic Pregnancies. Angiopoietin-like protein 6 (ANGPTL6) is a hepatokine, which, in animal studies, improves insulin sensitivity and increases energy expenditure to counteract insulin resistance. Evaluate in a human population, the role of serum ANGPTL6 in gestational diabetes mellitus (GDM) or its presence in fetal circulation. A total of 190 women (115 controls and 75 GDM) and their offspring were studied. Insulin, glucose, ANGPTL6, retinol binding protein 4 (RBP4), and retinol, as well as leptin and adiponectin, were determined in maternal serum obtained at term and from umbilical artery blood at delivery. At term, pregnant women with GDM showed higher serum concentrations of ANGPTL6, insulin, homeostatic model assessment, and apo-RBP4 (free RBP4) than controls but not of glucose, which remained similar in both groups. Also, in arterial cord serum, ANGPTL6 concentration was increased in GDM neonates with respect to the control group (201 ± 12 ng/mL vs 119 ± 8 ng/mL, respectively). No effect of maternal insulin treatment of some GDM mothers in neonates of either sex on ANGPTL6 levels was observed. In GDM, circulating ANGPTL6 showed no correlation with glucose or insulin concentration or with neonatal adiposity. However, in control pregnancies, the variation in glucose concentration was positively correlated with ANGPTL6 concentration, both in maternal and in cord samples, and cord ANGPTL6 was negatively correlated with neonatal fat mass. Furthermore, in control pregnant women, serum concentrations of ANGPTL6 and apo-RBP4 were negatively correlated. Serum ANGPTL6 levels are associated with maternal glucose homeostasis and fetal adiposity in normal pregnancy. ANGPTL6 levels in maternal and cord serum GDM pregnancy at term are increased, although its mechanism and physiological role are unknown yet.

Functionalized luminescent covalent organic frameworks hybrid material as smart nose for the diagnosis of Huanglongbing. Quantitative identification of several volatile organic compounds (VOCs) associated with the same disease provides a strong guarantee of the accurate analysis of the disease. Designing a single luminescent material to interact differently with multiple analytes can generate response patterns with remarkable diversity. Here, a highly green luminescent imine-based 2D COF (TtDFP) is designed and synthesized. TtDFP has ultrasensitive detection performance for trace water in organic solvent. Constructing a ratiometric fluorescence sensor can improve sensitivity for detecting analytes. To contrast the fluorescence signals of Eu3+ and COFs in sensing assays, a simple postsynthetic modification (PSM) method is used to introduce Eu3+ into TtDFP. The obtained red luminescent hybrid material Eu3+@TtDFP EVA film can be a fluorescent nose capable of "sniffing out" and quantifying VOCs (GA and PhA) associated with Huanglongbing (HLB, a devastating disease of citrus) at ppb levels. This work provides a technique of developing functionalized COF hybrid material to facilitate the distinction of various VOCs, which can also be extended to monitor the levels of other VOCs relevant to human health.

Genetic redundancy of 4-hydroxybenzoate 3-hydroxylase genes ensures the catabolic safety of Pigmentiphaga sp. H8 in 3-bromo-4-hydroxybenzoate-contaminated habitats. Genetic redundancy is prevalent in organisms and plays important roles in the evolution of biodiversity and adaptation to environmental perturbation. However, selective advantages of genetic redundancy in overcoming metabolic disturbance due to structural analogues have received little attention. Here, functional divergence of the three 4-hydroxybenzoate 3-hydroxylase (PHBH) genes (phbh1~3) was found in Pigmentiphaga sp. strain H8. The genes phbh1/phbh2 were responsible for 3-bromo-4-hydroxybenzoate (3-Br-4-HB, an anthropogenic pollutant) catabolism, whereas phbh3 was primarily responsible for 4-hydroxybenzoate (4-HB, a natural intermediate of lignin) catabolism. 3-Br-4-HB inhibited 4-HB catabolism by competitively binding PHBH3 and was toxic to strain H8 cells especially at high concentrations. The existence of phbh1/phbh2 not only enabled strain H8 to utilize 3-Br-4-HB but also ensured the catabolic safety of 4-HB. Molecular docking and site-directed mutagenesis analyses revealed that Val199 and Phe384 of PHBH1/PHBH2 were required for the hydroxylation activity towards 3-Br-4-HB. Phylogenetic analysis indicated that phbh1 and phbh2 originated from a common ancestor and evolved specifically in strain H8 to adapt to 3-Br-4-HB-contaminated habitats, whereas phbh3 evolved independently. This study deepens our understanding of selective advantages of genetic redundancy in prokaryote's metabolic robustness and reveals the factors driving the divergent evolution of redundant genes in adaptation to environmental perturbation.

Understanding the effect of structural changes on slow magnetic relaxation in mononuclear octahedral copper(II) complexes. Current advances in molecular magnetism are aimed at the construction of molecular nanomagnets and spin qubits for their utilization as high-density data storage materials and quantum computers. Mononuclear coordination compounds with low spin values of S = ½ are excellent candidates for this endeavour, but knowledge of their construction via rational design is limited. This particularly applies to the single copper(II) spin center, having been only recently demonstrated to exhibit slow relaxation of magnetisation in the appropriate octahedral environment. We have thus prepared a unique organic scaffold that would allow one to gain in-depth insight into how purposeful structural differences affect the slow magnetic relaxation in monometallic, transition metal complexes. As a proof-of-principle, we demonstrate how one can construct two, structurally very similar complexes with isolated Cu(II) ions in an octahedral ligand environment, the magnetic properties of which differ significantly. The differences in structural symmetry effects and in magnetic relaxation are corroborated with a series of experimental techniques and theoretical approaches, showing how symmetry distortions and crystal packing affect the relaxation behaviour in these isolated Cu(II) systems. Our unique organic platform can be efficiently utilized for the construction of various transition-metal ion systems in the future, effectively providing a model system for investigation of magnetic relaxation via targeted structural distortions.

T1rho, T2, and T2* relaxation time based on grading of intervertebral disc degeneration. Previous studies have explored the biochemical changes of disc degeneration and its relevance in low back pain using various quantitative magnetic resonance imaging (MRI) techniques. However, quantitative evaluation of intervertebral disc (IVD) with MRI such as T1rho, T2, and T2* have not been previously analyzed and compared directly in the same patients. To investigate T1rho, T2, and T2* of IVD degeneration in the same patients, reveal the correlation coefficients of these values, and evaluate which values are more sensitive to detect the degree of IVD degeneration. The participants were 55 patients who underwent MRI examinations which the investigator classified the degree of IVD degeneration according to the Pfirrmann classification. The T1rho, T2, and T2* values of IVD were analyzed for their classification and were compared. T1rho, T2, and T2* values were 74.3 ± 7.1, 61.2 ± 6.7, and 46.5 ± 16.3 ms (grade II); 61.6 ± 11.8, 48.9 ± 8.2, and 34.1 ± 11.8 ms (grade III); 50.8 ± 10.8, 38.9 ± 9.8, and 25.4 ± 8.1 ms, (grade IV); 44.5 ± 13.3, 34.8 ± 9.5, and 11.2 ± 6.6 ms (grade V), respectively. Those values significantly decreased with increasing grades, but T1rho and T2 values for grades IV and V were not different. The T1rho and T2 values were excellent for the evaluation of initial to moderate IVD degeneration with water and proteoglycan content. In contrast, the T2* value was suitable for detailed evaluation of progressive IVD, even with poor water content.

Role of intrapulmonary artery septation in univentricular hearts. The optimal management of functionally univentricular hearts with a significant unbalanced pulmonary blood flow is unclear. The role of cavopulmonary shunt in the rehabilitation of hypoplastic pulmonary arteries is limited. Intrapulmonary artery septation is a technique, wherein a systemic-to-pulmonary artery shunt provides an additional source of blood flow to rehabilitate the hypoplastic pulmonary artery. We report a case of functionally univentricular heart with hypoplastic left pulmonary artery following a cavopulmonary shunt in whom intrapulmonary artery septation resulted in adequate growth of the left pulmonary artery.

Nuclear magnetic resonance spectroscopy in extra virgin olive oil authentication. Extra virgin olive oil (EVOO) is a high-quality product that has become one of the stars in the food fraud context in recent years. EVOO can encounter different types of fraud, from adulteration with cheaper oils to mislabeling, and for this reason, the assessment of its authenticity and traceability can be challenging. There are several officially recognized analytical methods for its authentication, but they are not able to unambiguously trace the geographical and botanical origin of EVOOs. The application of nuclear magnetic resonance (NMR) spectroscopy to EVOO is reviewed here as a reliable and rapid tool to verify different aspects of its adulteration, such as undeclared blends with cheaper oils and cultivar and geographical origin mislabeling. This technique makes it possible to use both targeted and untargeted approaches and to determine the olive oil metabolomic profile and the quantification of its constituents.

High-performance hierarchical O-SnS/I-ZnIn2S4 photodetectors by leveraging the synergy of optical regulation and band tailoring. Low light absorption and limited carrier lifetime are critical obstacles inhibiting further performance improvement of 2D layered material (2DLM) based photodetectors, while scalable fabrication is an ongoing challenge prior to commercialization from the lab to market. Herein, wafer-scale SnS/ZIS hierarchical nanofilms, where out-of-plane SnS (O-SnS) is modified onto in-plane ZIS (I-ZIS), have been achieved by pulsed-laser deposition. The derived O-SnS/I-ZIS photodetector exhibits markedly boosted sensitivity as compared to a pristine ZIS device. The synergy of multiple functionalities contributes to the dramatic improvement, including the pronounced light-trapping effect of O-SnS by multiple scattering, the high-efficiency spatial separation of photogenerated electron-hole pairs by a type-II staggered band alignment and the promoted carrier transport enabled by the tailored electronic structure of ZIS. Of note, the unique architecture of O-SnS/I-ZIS can considerably expedite the carrier dynamics, where O-SnS promotes the electron transfer from SnS to ZIS whilst the I-ZIS enables high-speed electron circulation. In addition, the interlayer transition enables the bridging of the effective optical window to telecommunication wavelengths. Moreover, monolithic integration of arrayed devices with satisfactory device-to-device variability has been encompassed and a proof-of-concept imaging application is demonstrated. On the whole, this study depicts a fascinating functional coupling architecture toward implementing chip-scale integrated optoelectronics.

Use of diffusion tensor imaging as a prognostic biomarker after decompression surgery for carpal tunnel syndrome. Magnetic resonance diffusion tensor imaging (MR-DTI) has been increasingly applied for carpal tunnel syndrome (CTS) diagnosis, but relatively little is known about the effect of CTS treatment on median nerve (MN) integrity and functional outcome prediction. To assess how structural changes in MR-DTI of the MN correlates with symptom severity, functional status, and electrophysiological parameters in patients suffering from CTS before and after decompression surgery. Nine wrists were prospectively enrolled to perform MR-DTI pre- and postoperatively. The apparent diffusion coefficients (ADC) and fractional anisotropy (FA) of the MN were examined in three different regions-distal radioulnar joint, pisiform bone, and hamate bone-and correlated with clinical and electrophysiological parameters. Postoperatively, mean Boston Carpal Tunnel Questionnaire scores decreased 1.55 points (range = 0.08-3; P = 0.0172) and 1.01 points (-0.13 to 1.88; P = 0.0381) in the symptomatic and functional domains, respectively. Postoperative clinical improvement was reflected in proximal FA elevation (P = 0.0078), but not in diffusivity in comparison to baseline examination. Preoperative electrophysiological parameters were correlated with a reduction in the pre- (sensory latencies [rho = -0.6826; P = 0.0312]) and postoperative (motor latencies [rho = -0.7488; P = 0.0325]) distal FA values. Higher sensory amplitudes indicated higher postoperative proximal FA values (rho = 0.7618; P = 0.0280) ​​and lower postoperative proximal ADC values (rho = -0.9047; P = 0.0020). Our study demonstrated that pre- and postoperative proximal FA values are useful biomarkers for the structural evaluation of the MN in patients with CTS. Symptomatic improvement can be better predicted by analyzing FA changes.

Odontogenic Sinusitis is a Common Cause of Operative Extra-Sinus Infectious Complications. Orbital, intracranial, and osseous extra-sinus complications can arise from bacterial or fungal sinusitis. Odontogenic sinusitis (ODS) can cause extra-sinus complications, but its prevalence remains poorly characterized. To determine the frequency of ODS as a cause of operative extra-sinus infectious complications and describe clinical features of all complicated sinusitis cases. A multi-institutional retrospective review was performed on all operative sinusitis-related extra-sinus complications from 2011 to 2020. ODS was diagnosed by sinus computed tomography (CT) and dental evaluations when available. Demographics, complication types, sinusitis etiologies, and various clinical features were analyzed. Forty-five patients were included (mean age 55.5 years, 56% male). Of the extra-sinus complications, 40% were orbital only, 22% intracranial only, 13% osseous only, and 25% involved combined complications. The 2 most common causes of extra-sinus complications were ODS (40%) and mucopyocele (27%). When invasive fungal etiologies were excluded, and only unilateral maxillary opacification on CT was considered, nearly 60% of extra-sinus complications were due to ODS. Unilateral maxillary sinus opacification on CT was present in 100% of complicated ODS compared to 44% of nonodontogenic cases, and oral anaerobes were only identified in ODS cases. No complicated ODS patients underwent dental interventions during hospitalization. ODS was the most common cause of operative extra-sinus infectious complications. Clinicians should consider ODS high on the differential diagnosis of all patients presenting with complicated sinusitis, especially when sinusitis is unilateral and invasive fungal infection is not suspected.

Synthesis, characterisation and reactivity of group 2 complexes with a thiopyridyl scorpionate ligand. Herein we report the reactivity of the proligand tris(2-pyridylthio)methane (HTptm) with various Alkaline Earth (AE) reagents: (1) dialkylmagnesium reagents and (2) AE bis-amides (AE = Mg-Ba). Heteroleptic complexes of general formulae [Mg(Tptm)(R)] (R = Me, nBu; Tptm = {C(S-C5H4N)3}-) and [AE(Tptm)(N'')] (AE = Mg-Ba; N'' = {N(SiMe3)2}-) were targeted from the reaction of HTptm with R2Mg or [AE(N'')2]2. Reaction of the proligand with dialkylmagnesium reagents led to formation of [{Mg(κ3C,N,N-C{Bu}{S-C5H4N}2)(μ-S-C5H4N)}2] (1) and [{Mg(κ3C,N,N-C{Me}{S-C5H4N}2)(μ-OSiMe3)}2] (2) respectively, as a result of a novel transfer of an alkyl group onto the methanide carbon with concomitant C-S bond cleavage. However, reactivity of bis-amide precursors for Mg and Ca did afford the target species [AE(Tptm)(N'')] (3-AE; AE = Mg-Ca), although these proved susceptible to ligand degradation processes. DFT calculations show that alkyl transfer in the putative [Mg(Tptm)(nBu)] (1m') system and amide transfer in 3-Ca is a facile process that induces C-S bond cleavage in the Tptm ligand. 3-Mg and 3-Ca were also tested as catalysts for the hydrophosphination of selected alkenes and alkynes, including the first example of mono-hydrophosphination of 4-ethynylpyridine which was achieved with high conversions and excellent regio- and stereochemical control.

Hepatocellular carcinomas in captive prosimians. We performed a retrospective examination of spontaneous hepatocellular carcinomas (HCCs) (primary and metastatic tumors) in 14 captive prosimians brought to the Veterinary Medical Diagnostic Laboratory in North Carolina State University over a period of 11 years (2003 to 2014) to characterize the tumors. These animals are endangered primates; a better understanding of the main fatal neoplasms is crucial. In addition to the histologic evaluation, an immunohistochemical study was also performed, using a hepatocyte marker (hepatocyte paraffin 1 [HepPar-1]) and 2 cholangiocyte markers (keratin 7 [K7] and keratin 19 [K19]), in an attempt to identify a specific profile for HCCs with metastatic behavior. Six of the 14 HCCs had pulmonary metastases. The most frequent histopathological findings were a trabecular pattern (14/14, 100%), presence of multinucleated cells (12/14, 85.7%), and foci of extramedullary hematopoiesis (9/14, 64.3%). The mitotic count was significantly higher in the metastatic HCCs (P < .05). HepPar-1 was detected in all primary and metastatic HCCs, with a strong intensity of staining. Labeling for K7 and K19 was positive in 12 HCCs (85.7%) and 1 HCC (7.1%), respectively. Contrary to the less aggressive HCCs, most of the metastatic HCCs (5/6) expressed K7 in more than 15% of cells. The percentage of K7-positive neoplastic hepatocytes was significantly higher in metastatic HCCs. This study suggests that K7 might be a prognostically relevant marker in HCCs of captive prosimians.

Evaluation of clonality from multiple anatomic sites in canine epitheliotropic T cell lymphoma. Canine epitheliotropic cutaneous T-cell lymphoma (eCTCL) is thought to represent a disease homologue to human mycosis fungoides (MF). In human MF, neoplastic cells are phenotypically consistent with resident effector memory T cells, a population that remains for an extended period within tissue without circulating. Dogs with eCTCL often present with lesions in multiple locations, raising the question of whether the neoplasm is of the same T-cell subpopulation or not. To characterize the antigen receptor gene rearrangements of lymphocytes from skin and blood of dogs with eCTCL to determine if neoplastic clones are identical. Fourteen dogs with eCTCL. Histological and immunohistochemical examination, and PCR for antigen receptor rearrangement (PARR) for T-cell receptor gamma (TRG) performed on multiple cutaneous biopsy samples and blood. All skin biopsies contained cluster of differentiation (CD)3-positive neoplastic lymphocytes. Within individual dogs, all skin biopsies revealed identical TRG clonality profiles, suggesting that the same neoplastic clone was present in all sites. In the blood, a matching clone was found in six of 14 dogs, a unique clone was observed in nine of 14 dogs, and no clone was detected in two of 14 dogs. These findings show that canine eCTCL lesions in multiple locations harbour the same neoplastic clone, neoplastic lymphocytes do not remain fixed to the skin and instead can circulate via blood, differing clones can be identified in skin versus blood, and circulating neoplastic cells can be detected without lymphocytosis.

Overrepresentation of Young Indigenous Offenders: Differences in Criminogenic Risk/Needs and Implications for Practice. Indigenous youth are overrepresented in the Australian criminal justice system, yet little is known about how they differ from non-Indigenous youth in terms of criminogenic risk and need profiles in relation to reoffending. The aim of the study was to examine the differences between Indigenous and non-Indigenous youth in terms of criminogenic risk and need profiles. This paper expands on findings of our previous study. and present the results of two analyses. The first is a comparative analysis of the differences in criminogenic risk and need factors in a sample of 4,653 youth. Results raise questions about how Indigenous and non-Indigenous youth differ on type of criminogenic needs and how risk/needs are defined in an Indigenous context. The second analysis examines the predictive validity of a shortened version of the YLS/CMI in a subsample of 921 youth. Results show that a specific combination of five items for Indigenous youth corresponds to an improvement in AUC scores from c. = 0.65 for the full version to c. = 0.73. For non-Indigenous youth, the selected set of five items corresponds to an improvement in AUC scores from c. = 0.66 for the full version of the YLS/CMI to c. = 0.73. Implications of these findings for research, policy, and reducing Indigenous overrepresentation are discussed.

How epidemic information and policy information impact anti-infection behaviors: a cross-cultural study under social influence framing. Three preregistered experiments examined to what extent information about an epidemic situation provided by experts and information about anti-infection policies promoted by governments/media influenced anti-infection behaviors. The above effects were examined among populations from different countries (in Experiments 2 and 3) and across self-construals (in Experiment 3). In three experiments, participants (N =706) were presented with a scenario where experts provided (or did not provide) information about an epidemic situation and governments/media promoted (or did not promote) information about anti-infection policies. After that, participants indicated their willingness to adopt anti-infection behaviors. Results across three experiments showed that both types of information independently increased participants' anti-infection behaviors. In Experiments 2 and 3, we further found that the epidemic information had a larger impact on inducing anti-infection behaviors than the policy information, which was robust and consistent across countries and self-construals. Findings were discussed under the framework of social influence and in terms of practical implications for pandemic situations like the COVID-19.

Immune-Cell-Derived Exosomes for Cancer Therapy. Exosomes are a type of extracellular vesicles secreted by cells in normal or pathological conditions for cell-cell communication. With immunomodulatory characteristics and potential therapeutic properties, immune-cell-derived exosomes play an important role in cancer therapy. They express various antigens on their surface, which can be employed for antigen presentation, immunological activation, and metabolic regulation, leading to the killing of cancerous cells. In addition, immune-cell-derived exosomes have received extensive attention as a drug delivery platform in effective antitumor therapy due to their excellent biocompatibility, low immunogenicity, and high loading capacity. In this review, the biological and therapeutic characteristics of immune-cell-derived exosomes are comprehensively outlined. The antitumor mechanism of exosomes secreted by immune cells, including macrophages, dendritic cells, T cells, B cells, and natural killer cells, are systematically summarized. Moreover, the applications of immune-cell-derived exosomes as nanocarriers to transport antitumor agents (chemotherapeutic drugs, genes, proteins, etc.) are discussed. More importantly, the existing challenges of immune-cell-derived exosomes are pointed out, and their antitumor potentials are also discussed.

Antibacterial silver and gold complexes of imidazole and 1,2,4-triazole derived N-heterocyclic carbenes. A series of gold(I) (4a-4h, 5a-5b) and silver(I) (3a-3h) complexes of 1,2,4-triazolylidene and imidazolylidene based N-heterocyclic carbene ligands were prepared and the antibacterial activities of these complexes have been evaluated. The complexes were characterised using 1H-NMR, 13C-NMR, HRMS and in the cases of 3a, 3c, 4b and 5b by X-ray crystallography. The gold(I) complexes with phenyl substituents (4a-4d) were found to have potent antibacterial activity against Gram-positive bacteria, with the complexes of the 1,2,4-triazolylidene ligands being more active (4c, MIC = 4-8 μg mL-1 against Enterococcus faecium and 2 μg mL-1 against Staphylococcus aureus) than the analogous imidazolylidene complexes 4a and 4b (4a, MIC = 64 μg mL-1 against E. faecium and 2-4 μg mL-1 against S. aureus). Two of the silver(I) complexes have promising antibacterial activity against Acinetobacter baumannii (3f, MIC = 2-4 μg mL-1 and 3g, MIC = 2 μg mL-1). Silver(I) complex 3f and gold(I) complex 4c were tested against multi-drug resistant bacterial strains and high levels of antibacterial activity were observed. The potential for antibacterial resistance to develop against these metal containing complexes was investigated and significantly, no resistance was observed upon continuous treatment, whilst resistance was developed against the widely used broad-spectrum antibiotic ciprofloxacin in the same bacterial strains, under the conditions tested. The solution and gas phase stabilities of the complexes have been investigated using a combination of 1H-NMR, HRMS and detailed computational mechanistic studies were undertaken to gain insights into the possible decomposition reactions for silver complexes in aqueous solution.

Conceptualisations of COPD self-management: A narrative review of the research literature. To examine how self-management is conceptualised in the research literature on chronic obstructive pulmonary disease (COPD). A narrative review was undertaken to search the research literature on COPD self-management. Ten databases (2000-2021) were searched for published texts. Sixty-two articles met the inclusion criteria. A thematic analysis was conducted of the literature. Three conceptualisations of COPD self-management were identified: 1) a dominant medicocentric conceptualisation which represented self-management as medical in focus; 2) a less dominant experiential conceptualisation that viewed it as arising from the experiences of people living with COPD; and 3) a smaller body of literature that attempted to integrate medicocentric and experiential conceptualisations of self-management. The dominance of the medicocentric conceptualisation of self-management and the polarisation of medicocentric and experiential perspectives were striking. An integrated conceptualisation of self-management has the potential to unite these competing perspectives and promote collaborative relationships between individuals and professionals, so long as the underlying values informing it are made explicit. However, there is a dearth of literature on this approach and it would benefit from more attention. Methods such as Co-production and the Personal Outcomes Approach offer the potential to support an integrated perspective in clinical practice.

Sagittal Growth Restriction of the Midface Following Isolated Cleft Lip Repair: A Systematic Review and Meta-Analysis. Midface hypoplasia (MFH) is a long-term sequela of cleft lip and palate repair, and is poorly understood. No study has examined the aggregate data on sagittal growth restriction of the midface following repair of the lip, but not palate, in these patients. A systematic review of 3780 articles was performed. Twenty-four studies met inclusion criteria and 11 reported cephalometric measurements amenable to meta-analysis. Patients with Veau class I-III palatal clefts were included so long as they had undergone only lip repair. Groups were compared against both noncleft and unrepaired controls. Cephalometrics were reported for 326 patients (31.3% female). Noncleft controls had an average SNA angle of 81.25° ± 3.12°. The only patients demonstrating hypoplastic SNA angles were those with unilateral CLP with isolated lip repair (77.4° ± 4.22°). Patients with repaired CL had SNA angles similar to noncleft controls (81.4° ± 4.02°). Patients with unrepaired CLP and CL tended toward more protruding maxillae, with SNA angles of 83.3° ± 4.04° and 87.9° ± 3.11°, respectively. Notably, when comparing SNA angles between groups, patients with CLP with isolated lip repair had significantly more hypoplastic angles compared to those with repaired CL (P < .0001). Patients with CLP with isolated lip repair were also more hypoplastic than noncleft controls (P < .0001). In contrast, there was no significant difference between the SNA of patients with repaired CL and controls (P = .648). We found that cleft lip repair only appeared to contribute to MFH in the setting of concurrent cleft palate pathology, suggesting that scarring from lip repair itself is unlikely to be the predominant driver of MFH development. However, studies generally suffered from inadequate reporting of timing, technique, follow-up time, and cleft severity.

Whole genome sequencing and inheritance-based variant filtering as a tool for unraveling missing heritability in pediatric cancer. Survival rates for pediatric cancer have significantly increased the past decades, now exceeding 70-80% for most cancer types. The cause of cancer in children and adolescents remains largely unknown and a genetic susceptibility is considered in up to 10% of the cases, but most likely this is an underestimation. Families with multiple pediatric cancer patients are rare and strongly suggestive for an underlying predisposition to cancer. The absence of identifiable mutations in known cancer predisposing genes in such families could indicate undiscovered heritability. To discover candidate susceptibility variants, whole genome sequencing was performed on germline DNA of a family with two children affected by Burkitt lymphoma. Using an inheritance-based filtering approach, 18 correctly segregating coding variants were prioritized without a biased focus on specific genes or variants. Two variants in FAT4 and DCHS2 were highlighted, both involved in the Hippo signaling pathway, which controls tissue growth and stem cell activity. Similarly, a set of nine non-coding variants was prioritized, which might contribute, in differing degrees, to the increased cancer risk within this family. In conclusion, inheritance-based whole genome sequencing in selected families or cases is a valuable approach to prioritize variants and, thus, to further unravel genetic predisposition in childhood cancer.

First case of Wohlfahrtiimonas chitiniclastica isolation from a patient with a foot ulcer infection in Belgium. We present the first documented isolation of Wohlfahrtiimonas chitiniclastica from a patient in Belgium. The isolate was identified as W. chitiniclastica using matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF MS) and 16S rRNA gene sequencing. Our methodology corresponds with the previous conclusions on the superior performance of MALDI-TOF MS for bacterial identification. The patient was treated with amoxicillin/clavulanate and was discharged home after wound management. Although the clinical relevance of the isolate in our case is inconclusive, the pathogenicity of such isolate has been described and therefore must be considered as a potential pathogen in chronic and ulcerating wound cultures.

Nonlinear Optical Activities in Two-Dimensional Gallium Sulfide: A Comprehensive Study. The nonlinear optical (NLO) properties of two-dimensional (2D) materials are fascinating for fundamental physics and optoelectronic device development. However, relatively few investigations have been conducted to establish the combined NLO activities of a 2D material. Herein, a study of numerous NLO properties of 2D gallium sulfide (GaS), including second-harmonic generation (SHG), two-photon excited fluorescence (TPEF), and NLO absorption are presented. The layer-dependent SHG response of 2D GaS identifies the noncentrosymmetric nature of the odd layers, and the second-order susceptibility (χ2) value of 47.98 pm/V (three-layers of GaS) indicates the superior efficiency of the SHG signal. In addition, structural deformation induces the symmetry breaking and facilitates the SHG in the bulk samples, whereas a possible efficient symmetry breaking in the liquid-phase exfoliated samples results in an enhancement of the SHG signal, providing prospective fields of investigation for researchers. The generation of TPEF from 800 to 860 nm depicts the two-photon absorption characteristics of 2D GaS material. Moreover, the saturable absorption characteristics of 2D GaS are realized from the largest nonlinear absorption coefficient (β) of -9.3 × 103, -91.0 × 103, and -6.05 × 103 cm/GW and giant modulation depths (Ts) of 24.4%, 35.3%, and 29.1% at three different wavelengths of 800, 1066, and 1560 nm, respectively. Hence, such NLO activities indicate that 2D GaS material can facilitate in the technical advancements of future nonlinear optoelectronic devices.

Rational design of highly efficient MXene-based catalysts for the water-gas-shift reaction. Water molecules linked by hydrogen bonds are responsible for the high efficiency of bi-functional catalysts for the water-gas-shift (WGS) reaction because water can act as a proton transfer medium. Herein, we propose an associative pathway for the WGS reaction assisted by water to realize hydrogen production. Based on this pathway, we show by first-principles calculations that a large family of oxygen-terminated two-dimensional transition metal carbides and nitrides (MXenes) deposited on Au clusters are promising catalysts for the WGS reaction. Remarkably, the rate-determining barriers for *CO → *COOH on Au/Mn+1XnO2 are in the range from 0.15 eV to 0.39 eV, indicating that WGS can occur at much lower temperatures. Furthermore, a comprehensive microkinetic model is constructed to describe the turnover frequencies (TOF) for the product under the steady-state conditions. More importantly, there is a perfect linear scaling relationship between the rate-determining barriers of the WGS and the free energy of the adsorbed hydrogen. Besides, the potential energy diagrams for CO reforming reveal that the F terminations introduced in experiments have only a slight influence on the catalytic performance of the oxygen-terminated MXenes. Our work not only opens a new avenue towards the WGS reaction but also provides many ideal catalysts for hydrogen production.

An Interpretative Phenomenological Analysis on the Experience of Probation Officers in Managing People With Antisocial Personality Disorder. People who are managed by the National Probation Service and convicted of high risk offences will often meet criteria for antisocial personality disorder and have complex psychosocial needs; this group of people present with high risk behavior which may professionals have been reluctant to work with in the past who are associated with higher rates of recidivism. This study investigated the experiences of probation officers in managing people who meet the criteria for Anti Social Personality Disorder. Semi structured interviews were conducted with six participants to capture their experiences of working with this population, the challenges they faced, and coping mechanisms employed, through analysis using Interpretative Phenomenological Analysis (IPA). Three superordinate themes were identified which revealed participants internal feeling, strategies employed, and external challenges. They spoke about internal negative feelings, specifically feeling controlled, having mistrust, a lack of confidence, being overwhelmed with emotion, and experiencing a fear of risk behaviors. Other themes involved external pressures as well as different coping responses. Implications are discussed to help probation officers to understand this population, for the organization to support staff to work with challenging behaviors and prevent burn out, to enable positive outcomes, and for potentially reducing reoffending.

Unexpected toroidal micelles formed from St/MMA gradient copolymers. Toroidal micelles are of great interest and rarely observed in gradient copolymer systems. Herein, we report massive toroidal micelles formed from styrene (St)/methyl methacrylate (MMA) gradient copolymers using a common solvent mixing method followed by a cooling-heating procedure. Furthermore, we demonstrate that the obtained toroidal morphology is sensitively dependent on a heat treatment procedure. Solely spherical micelles are obtained by a common solvent mixing method. These spherical micelles could be transformed into toroidal micelles via vesicles during a cooling-heating process. When a reverse heating-cooling process is adopted, no toroidal micelles formed. Thus, these results add new members to the family of toroidal micelles and reveal pathway dominating morphologies in gradient copolymer micelles.

OCT imaging of macular cysts and treatment response with nepafenac in mucopolysaccharidosis type 1. Mucopolysaccharidosis Type I (MPS I) is an autosomal recessive lysosomal storage disorder characterized by a defect in the enzyme alpha-L-iduronidase. Glycosaminoglycan accumulation causes ocular involvement such as corneal clouding or pigmentary retinopathy. Here we report bilateral macular cysts in mucopolysaccharidosis type I (MPS I) that responds to nepafenac treatment. Retrospective case report. A 27-year-old woman with MPS I (Scheie phenotype) was complaining of slightly blurred vision. She had been on alpha-L-iduronidase enzyme replacement therapy for ten years. Best-corrected visual acuity was 20/25 in both eyes. Biomicroscopy was normal. Dilated fundus examination revealed pigmentary retinopathy. Optical coherence tomography (OCT) detected macular cysts in inner and outer nuclear layers, with preservation of ellipsoid zone and IS/OS line. There was no dye leakage on fluorescein angiography. Macular cysts regressed partially after one month with topical nepafenac 0.1% four times a day. BCVA improved to 20/20 in both eyes. This is the first report of bilateral macular cysts that was demonstrated with OCT and treated with topical nepafenac in a patient with MPS I. Because the symptoms of our patient were mild, large-scaled cohort studies are required to ascertain the real prevalence of macular cysts in MPS I. It may also be beneficial to do more research on the possible benefits of nepafenac on the retinal manifestations of MPS.

Angiogenic footprints in diabetic retinopathy: opportunities for drug development. Diabetic retinopathy is one of the withering disorders that has been making the lives of patients miserable. Arising as a result of chronic high blood sugar levels in diabetes patients, retinopathy has become a major reason causing permanent blindness, retinal detachment, vitreous humor, rage, or glaucoma among patients. Angiogenesis being the major culprit behind the development of this condition is the growth of new blood vessels from the earlier ones existing. The abnormal growth and poor development of blood vessels also lead to aggravation of the conditions, with vascular endothelial growth factor (VEGF) playing a major role in the process. Various anti-angiogenic therapies or anti-VEGF therapies are being explored for the treatment of this condition. 4 widely explored drugs being-Bevacizumab, pegaptanib sodium, ranibizumab, and aflibercept. The review article tries to summarize studies illustrating the efficacy of these drugs in the treatment of diabetic retinopathy along with some of the herbal therapeutic paradigms displaying anti-angiogenic action that is being used to treat this condition.

[Formula: see text] Emotional reactivity and expressivity in young children with sex chromosome trisomies: evidence from psychophysiological and observational data. Although sex chromosomal trisomies (SCT) in children are highly prevalent and associated with an increased risk for neurodevelopmental difficulties including socio-emotional problems, little is known about underlying mechanisms that could drive this risk. Studying emotional reactivity and expressivity of young children with SCT in early childhood could identify deviations in early emotional development and potentially serve as risk markers to guide clinical care in developing interventions. Participants in the current study were 90 SCT children and 97 population-based controls, aged 1 to 7 years, who experienced a stress-inducing event in which physiological (heart rate) and observational data (expression of negative emotions) were collected. Results showed early disturbances in the emotion system of young children with SCT, in terms of blunted but prolonged emotional reactivity and a reduced emotional expressivity in response to stress. Further, the concordance between emotional reactivity (arousal response) and expressivity was significantly lower in SCT, compared to controls. Given the significant impact of emotions on adaptive day-to-day functioning, deviations in processing emotions could be an important underlying mechanism in explaining the heterogeneity and variability in developmental outcomes often described in individuals with SCT.

Ingroup and outgroup differences in face detection. Humans show improved recognition for faces from their own social group relative to faces from another social group. Yet before faces can be recognized, they must first be detected in the visual field. Here, we tested whether humans also show an ingroup bias at the earliest stage of face processing - the point at which the presence of a face is first detected. To this end, we measured viewers' ability to detect ingroup (Black and White) and outgroup faces (Asian, Black, and White) in everyday scenes. Ingroup faces were detected with greater speed and accuracy relative to outgroup faces (Experiment 1). Removing face hue impaired detection generally, but the ingroup detection advantage was undiminished (Experiment 2). This same pattern was replicated by a detection algorithm using face templates derived from human data (Experiment 3). These findings demonstrate that the established ingroup bias in face processing can extend to the early process of detection. This effect is 'colour blind', in the sense that group membership effects are independent of general effects of image hue. Moreover, it can be captured by tuning visual templates to reflect the statistics of observers' social experience. We conclude that group bias in face detection is both a visual and a social phenomenon.

Perspectives of Pediatric Community Health Workers: Roles, Successes, and Challenges. This multicenter qualitative study described the roles of 10 pediatric community health workers (CHWs) in their own words through exploration of the role features, successes, and challenges in pediatric health care settings across three urban U.S. cities (Philadelphia, New York City, and Cincinnati). Individual, semi-structured telephone interviews were conducted. Interviews described prominent features of the pediatric CHW role, which included taking a family-centered approach to goal setting and determining support needed, ensuring family goals stayed at the center of the work, and acting as a trusted figure for families to talk openly with. CHWs described their role as rewarding, believing in the work, and feeling a sense of fulfillment, and felt successful when families had positive outcomes, including when barriers were eliminated, resources were obtained, or independence was demonstrated by families. Challenges CHWs faced in their roles included establishing trust with families, managing the ever-changing family circumstances many families experience due to socioeconomic barriers, and managing limitations of protocol and restrictions within their roles. This study demonstrated numerous considerations for CHW practice in pediatric health care settings, in addition to considerations for pediatric-specific CHW program development and management. The primary policy implication of this study included a basis for increased funding for CHW programs in pediatric health care settings. This study also demonstrated a need for further research on the change CHWs effect within child and family systems outside of health care, such as schools and child welfare agencies.

Advancing the assessment of mindful eating: Exploring the psychometric properties and validating the mindful eating behaviour scale in English. Background: Mindful eating has been described as significant in motivating research and clinical outcomes in weight regulation and healthy eating. The use of psychometric tools to measure mindful eating is problematic, with results often leading to interpretations that are not reflective of mindful eating theory and fundamentals of mindfulness. Aim: In this research, we explored the Mindful Eating Behaviour Scale (MEBS) within a British sample to validate the factorial structure, and widen the use of a scale that appears appropriate for measuring mindful eating. Methods: A community sample (n = 742) was recruited via social media, and the findings supported the factorial structure proposed through the original Dutch sample. Predictive validity was also assessed, with the scale and subscales predicting fat and sugar consumption. Results: Cronbach's α values were acceptable and similar to the original findings, also supporting the internal consistency of the scale. Conclusion: While factorial structure, predictive validity and internal consistency propose a scale that can be adopted with English speaking populations, we propose the potential of furthering scientific inquiry on mindful eating research by highlighting the behavioural aspects of the scale.

Aminoalkoxy-substituted coumarins: Synthesis and evaluation for reactivation of inhibited human acetylcholinesterase. Reactivation of inhibited acetylcholinesterase remains an important therapeutic strategy for the treatment of poisoning by organophosphorus compounds, such as nerve agents or pesticides. Although drugs like obidoxime or pralidoxime have been used with considerable success, there is a need for new substances capable of reactivating acetylcholinesterase with a broader scope and increased efficacy. Possible screening candidates must fulfill two fundamental requirements: They must (i) show an affinity to acetylcholinesterase well balanced between sufficient binding and competitive inhibition and (ii) facilitate the nucleophilic cleavage of the phosphorylated catalytic serine residue. We attached a variety of nonaromatic primary and secondary amines to a coumarin core through selected alkoxy side linkers attached at coumarin positions 6 or 7 to obtain a small set of possible reactivators. Evaluation of their inhibition and reactivation potential in vitro showed some activity with respect to acetylcholinesterase inhibited by cyclosarin.

Occurrence of Streptomyces tauricus in mangrove soil of Mangalore region in Dakshina Kannada as a source for antimicrobial peptide. Microbial resistance and deprivation of the effective drugs have become the foremost problem that propels to seek out for advanced approach. This concept initiated a need to search for more effective antimicrobial compounds from reliable sources. The Streptomyces is grouped under phylum Actinobacteria and are considered prolific producers of antibiotics, around 70% of presently available antibiotics are contributed by Streptomyces alone. In this study, Mangroves of the Mangalore Coast offered a unique source for screening Actinomyces group of microorganisms. We investigated on the four soil samples collected from Mangrove swamps of Mangalore, Karnataka, India. Based on their culture traits, the 18 distinct Actinomyces isolates were analyzed through a series of morphological and biochemical tests on starch casein nitrate (SCN) media. Culture biomasses were subjected for intracellular protein extraction through acetone precipitation method; the extracted proteins from each Actinomyces isolate were examined for antimicrobial activity against test organisms. The isolate ANTB-YKMU4 showed potential antimicrobial activity against significant number of test organisms; Bacillus cereus, Proteus vulgaris, Staphylococcus aureus, Salmonella typhimurium, and Pseudomonas aeruginosa. The isolate ANTB-YKMU4 through 16 s rRNA gene sequence analysis was identified as Streptomyces tauricus strain with GenBank accession no. MW785875.1. The S. tauricus further cultivated for efficient biomass growth on SCN media for subsequent protein extraction and purification by a series of Electrophoretic and chromatographic techniques. Thus, by intracellular extractions from S. tauricus resulted in the identification of peptide with a molecular weight of 266 Da that was characterized by LC-MS.

Bioevaluation of quinoline-4-carbonyl derivatives of piperazinyl-benzothiazinones as promising antimycobacterial agents. The quinoline moiety remains a privileged antitubercular (anti-TB) pharmacophore, whereas 8-nitrobenzothiazinones are emerging potent antimycobacterial agents with two investigational candidates in the clinical pipeline. Herein, we report the synthesis and bioevaluation of 30 piperazinyl-benzothiazinone-based quinoline hybrids as prospective anti-TB agents. Preliminary evaluation revealed 24/30 compounds exhibiting substantial activity (minimum inhibitory concentration [MIC] = 0.06-1 µg/ml) against Mycobacterium tuberculosis (Mtb) H37Rv. Cytotoxicity analysis against Vero cells found these to be devoid of any significant toxicity, with the majority displaying a selectivity index of >80. Furthermore, potent nontoxic compounds, when screened against clinical isolates of drug-resistant Mtb strains, demonstrated equipotent inhibition with MIC values of 0.03-0.25 µg/ml. A time-kill study identified a lead compound exhibiting concentration-dependent bactericidal activity, with 10× MIC completely eliminating Mtb bacilli within 7 days. Along with acceptable aqueous solubility and microsomal stability, the optimum active compounds of the series manifested all desirable traits of a promising antimycobacterial candidate.

Pipeline embolization of complex, wide-necked middle cerebral artery bifurcation aneurysms: A single-center experience. To evaluate the performance of Pipeline Embolization Device (PED) in complex, wide-necked middle cerebral artery (MCA) bifurcation aneurysms. We performed a retrospective review of patients treated with PED for complex, wide-necked MCA bifurcation aneurysms between August 2016 and March 2021. In addition to demographic data, we collected aneurysmal neck width, dome-to-neck ratio, complications, and clinical and angiographic follow-up. The embolization degree of aneurysms was evaluated by O'Kelly-Marotta (OKM) grading scale, and the prognosis was assessed with the modified Rankin Scale (mRS). From August 2016 to March 2021, a total of 46 patients with 49 MCA bifurcation aneurysms in our center were enrolled, of whom all received PEDs successfully. The O'Kelly-Marotta (OKM) grading showed that post-procedure 15 patients (32.6%) were grade C, another 8 patients (17.4%) were grade D. Aneurysms with small remnant or complete occlusion were 50%, symptomatic ischemic events occurred in 3 (6.5%), and bleeding events in 1 (2.2%). 41 patients underwent a 6-month angiography follow-up, in which 7 patients (17.1%) remained OKM grade C and 30 patients (73.2%) achieved OKM grade D. Complete occlusion and small remnant aneurysms were up to 90.3%. 40 (97.6%) patients' mRS scores were 0, and 1 (2.4%) patient was 2. No new bleeding and ischemic events occurred during the 6-month. The Pipeline Embolization Device provides a safe and effective treatment alternative for complex, wide-necked MCA aneurysms. A larger number with longer-term follow-up data is needed for further verification.

E-CPR in Cardiac Arrest due to Accidental Hypothermia Using Intensivist Cannulators: A Case Series of Nine Consecutive Patients. Background: Severe accidental hypothermia (AH) accounts for over 1300 deaths/year in the United States. Early extracorporeal life support (ECLS) is recommended for hypothermic cardiac arrest. We describe the use of a rapid-deployment extracorporeal cardiopulmonary resuscitation (E-CPR) team using intensivist physicians (IPs) as cannulators and report the outcomes of consecutive patients cannulated for ECLS to manage cardiac arrest due to AH. Methods: We reviewed all patients managed with veno-arterial (V-A) ECLS for hypothermic cardiac arrest between January 1, 2017 and November 1, 2021. For each patient- age, sex, cause of hypothermia, initial core temperature, initial rhythm, time from arrest to cannulation, cannula configuration, pH, lactate, potassium, cannulation complications, duration of ECLS, hospital length of stay, mortality, and cerebral performance category (CPC) at discharge were reviewed. Results: Nine consecutive patients were identified that underwent V-A ECLS for cardiac arrest due to AH. Seven (78%) were witnessed arrests. Initial rhythm was ventricular fibrillation (VF) in eight patients and pulseless electrical activity (PEA) in one. The mean initial core temperature was 23.8 degrees Celsius. The mean time from arrest to cannulation was 58 min (range 17 to 251 min). There were no complications related to cannulation. The mean duration of ECLS was 39.1 h. All nine patients were discharged alive with a Cerebral Performance score of one or two. Conclusion: In this case series of consecutive patients reporting intensivist-deployed E-CPR for cardiac arrest due to AH, all patients survived to discharge with a favorable neurologic outcome. A rapidly available E-CPR team utilizing intensivist cannulators may improve outcomes in patients with cardiac arrest due to AH.

Introduction of Fluorine into Antitumor-Active Dinuclear Platinum(II) Complexes Leads to Modulation of In Vivo Antitumor Activity in Mice. Tetrazolato-bridged dinuclear platinum(II) complexes ([{cis-Pt(NH3)2}2(μ-OH)(μ-5-R-tetrazolato-N2,N3)]2+; tetrazolato-bridged complexes) show remarkable cytotoxic effects in vitro and antitumor activity in vivo. Here, we examined the structure-activity relationship of a series of fluorine-containing derivatives (R = CFH2, CF2H, or CF3), focusing on their lipophilicity, cellular accumulation, cytotoxicity, interactions with a nucleobase and double-stranded deoxyribonucleic acid, and in vivo antitumor efficacy. Fluorination had a little effect on the properties of the derivatives in vitro; however, marked differences in in vitro cytotoxicity and in vivo tumor growth inhibition activity were observed. In BALB/c mice bearing colon-26 tumors, the antitumor efficacies of the derivatives were markedly altered, even by changing the number of fluorine atoms by one. In addition, one derivative, [{cis-Pt(NH3)2}2(μ-OH)(μ-5-difluoromethyltetrazolato-N2,N3)](NO3)2, showed a significantly higher antitumor efficacy compared with oxaliplatin, a current first-line drug and the only platinum-based drug approved for the treatment of colon cancer. Together, the present results indicate that introducing fluorine into tetrazolato-bridged complexes may be useful for modulating in vivo activities.

Prevalence of, and factors associated with anaemia in children aged 1-3 years in Aceh, Indonesia: A cross-sectional study. Background: Child anaemia continues to represent a major public health challenge in lower-and-middle income countries. It has serious long-term consequences for child growth and development. In Indonesia, there was a 10% increase in the national prevalence of child anaemia between 2013 and 2018. Aim: This study aims to assess the prevalence of, and factors associated with anaemia among children aged one to three years in eight districts in Aceh Province, Indonesia. Methods: A cross-sectional study was conducted on a sample of 1148 mother-child dyads aged one to three years between November and December 2018. The sampling process involved a three-stage cluster sampling design using the probability proportionate to size methodology. Anaemia status was determined using haemoglobin level (Hb < 11.0 g/dL). Data were analysed using multivariable logistic regression to estimate adjusted odds ratios (aOR) and their 95% confidence intervals (95% CI) for associated factors. Results: The overall prevalence of anaemia was 76.1% (869/1142). 44.7% (510/1142) and 28.6% (327/1142) had moderate and mild anaemia, respectively. Child aged 12-24 months (aOR: 2.00, 95% CI: 1.26-3.17), not receiving routine immunisation (aOR: 2.62, 95% CI: 1.34-5.10), and maternal anaemia (aOR: 2.15, 95% CI: 1.59-2.90) were significantly associated with anaemia. Conclusion: The prevalence of anaemia among the children in this study was high, and was associated with child age, immunisation status, and maternal anaemia. These findings provide further insight into anaemia as a public health issue at a sub-national level in Indonesia and for development of targeted programmes to address associated risk factors of child anaemia.

Food insecurity and medication restricting behavior among persons with diabetes in the United States. Medication restricting behaviours are common among persons with diabetes increasing risk for poor health outcomes. Persons with diabetes are more likely to experience food insecurity than persons without diabetes. This study aimed to assess the relationship between food insecurity and medication restricting behaviour among persons with diabetes in the United States. Data from the 2019 National Health Interview Survey (NHIS) data conducted in the United States was used for this analysis. Medication restricting behaviour was assessed by questions asking whether four restricting behaviours were present (skipped medication, took less medication, delayed filling a prescription and/or took less medication due to cost). Food insecurity status was obtained through a 10-item scale and participants were categorized as either food secure, low food security, or very low food security. Poisson regression evaluated the relationship between medication restricting behaviour and food insecurity controlling for confounders. Participants with very low food security had a significantly higher mean number of medication restricting behaviours than participants who were food secure (adjusted mean ratio (AMR) = 4.01; 95% confidence interval (CI) = (3.09, 5.21)). Similarly, participants with low food security had a significantly higher mean ratio than participants who were food secure (AMR = 3.76; 95% CI = (2.86. 4.94). Persons with diabetes who have low or very low food security are at an increased risk for engaging in medication restricting behaviours.

Highly Ordered Porous Inorganic Structures via Block Copolymer Lithography: An Application of the Versatile and Selective Infiltration of the "Inverse" P2VP-b-PS System. A facile and versatile strategy was developed to produce highly ordered porous metal oxide structures via block copolymer (BCP) lithography. Phase separation of poly(2-vinylpyridine)-b-polystyrene (P2VP-b-PS) was induced by solvent vapor annealing in a nonselective solvent environment to fabricate cylindrical arrays. In this work, we thoroughly analyzed the effects of the film thickness, solvent annealing time, and temperature on the ordering of a P2VP-majority system for the first time, resulting in "inverse" structures. Reflectometry, atomic force microscopy, scanning electron microscopy, energy-dispersive X-ray spectroscopy, X-ray photoelectron spectroscopy (XPS), and transmission electron microscopy were used to characterize the formation of the highly ordered BCP morphology and the subsequently produced metal oxide film. At 40 min solvent annealing time, hexagonally close packed structures were produced with cylinder diameters ∼40 nm. Subsequently, the BCP films were infiltrated with different metal cations. Metal ions (Cr, Fe, Ni, and Ga) selectively infiltrated the P2VP domain, while the PS did not retain any detectable amount of metal precursor. This gave rise to a metal oxide porous structure after a UV/ozone (UVO) treatment. The results showed that the metal oxide structures demonstrated high fidelity compared to the BCP template and cylindrical domains presented a similar size to the previous PS structure. Moreover, XPS analyses revealed the complete elimination of the BCP template and confirmed the presence of the metal oxides. These metal oxides were used as hard masks for pattern transfer via dry etching as a further application. Silicon nanopores were fabricated mimicking the BCP template and demonstrated a pore depth of ∼50 nm. Ultimately, this strategy can be applied to create different inorganic nanostructures for a diverse range of applications, for example, solar cells, diodes, and integrated circuits. Furthermore, by optimizing the etching parameters, deeper structures can be obtained via ICP/RIE processes, leading to many potential applications.

Curcumin and carvacrol mediated photodynamic inactivation with 405 nm light emitting diodes (LEDs) on Salmonella Enteritidis. Photodynamic inactivation (PDI) has a potential application for food preservation that can minimize food pathogens posing risks to consumer health. This study aimed to evaluate the antibacterial activity of 405 nm light-emitting diodes (LEDs) illumination in the presence of carvacrol and curcumin against Salmonella Enteritidis and S. Enteritidis PT4 at different temperatures (4 °C, 25 °C and 37 °C) and time parameters (15 min, 30 min and 45 min) in the illumination system. Compared to their individual treatment, the decrease in the bacterial population was stronger in bacteria treated with LEDs + carvacrol or LEDs + curcumin. Co-application of carvacrol or curcumin with LEDs at 37 °C showed strong antibacterial activity against both bacteria depending on the application time. Co-application at 37 °C for 45 min completely inhibited the growth of S. Enteritidis. LEDs, curcumin, carvacrol applications alone or LEDs + curcumin, LEDs + carvacrol applications caused a decrease in bacterial population in proportion to the increase in the storage temperature and application times. These results showed that carvacrol or curcumin potentiates LEDs illumination therapy against both bacteria. Future studies on adapting the PDI system to control bacteria in a variety of foods may help develop novel strategies to fight against foodborne bacterial pathogens.

Nanoparticle Fraught Liposomes: A Platform for Increased Antibiotic Selectivity in Multidrug Resistant Bacteria. Increasing antibiotic concentrations within bacterial cells while reducing them in mammalian ones would ultimately result in an enhancement of antibacterial actions, overcoming multidrug resistance, all while minimizing toxicity. Nanoparticles (NPs) have been used in numerous occasions to overcome antibiotic resistance, poor drug solubility, and stability. However, the concomitant increase in antibiotic concentration in mammalian cells and the resultant toxicity are usually overlooked. Without compromising bacterial cell fusion, large liposomes (Lip) have been reported to show reduced uptake in mammalian cells. Therefore, in this work, small NP fraught liposomes (NP-Lip) were formulated with the aim of increasing NP uptake and antibiotic delivery in bacterial cells but not in mammalian ones. Small polylactic-co-glycolic acid NPs were therefore loaded with erythromycin (Er), an antibiotic with low membrane permeability that is susceptible to drug efflux, and 3c, a 5-cyanothiazolyl urea derivative with low solubility and stability. In vitro experiments demonstrated that the incorporation of small NPs into large Lip resulted in a reduction in NP uptake by HEK293 cells while increasing it in Gram-negative bacteria (Escherichia coli DH5α, E. coli K12, and Pseudomonas aeruginosa), consequently resulting in an enhancement of antibiotic selectivity by fourfold toward E. coli (both strains) and eightfold toward P. aeruginosa. Ocular administration of NP-Lip in a P. aeruginosa keratitis mouse model demonstrated the ability of Er/3c-loaded NP-Lip to result in a complete recovery. More importantly, in comparison to NPs, the ocular administration of NP-Lip showed a reduction in TNF-alpha and IL-6 levels, implying reduced interaction with mammalian cells in vivo. This work therefore clearly demonstrated how tailoring the nano-bio interaction could result in selective drug delivery and a reduction in toxicity.

Polygenic Risk Prediction in Diverticulitis. To derive and validate a polygenic risk score (PRS) to predict the occurrence and severity of diverticulitis and to understand the potential for incorporation of a PRS in current decision-making. PRS quantifies genetic variation into a continuous measure of risk. There is a need for improved risk stratification to guide surgical decision-making that could be fulfilled by PRS. It is unknown how surgeons might integrate PRS in decision-making. We derived a PRS with 44 single-nucleotide polymorphisms associated with diverticular disease in the UK Biobank and validated this score in the Michigan Genomics Initiative (MGI). We performed a discrete choice experiment of practicing colorectal surgeons. Surgeons rated the influence of clinical factors and a hypothetical polygenic risk prediction tool. Among 2812 MGI participants with diverticular disease, 1964 were asymptomatic, 574 had mild disease, and 274 had severe disease. PRS was associated with occurrence and severity. Patients in the highest PRS decile were more likely to have diverticulitis [odds ratio (OR)=1.84; 95% confidence interval (CI), 1.42-2.38)] and more likely to have severe diverticulitis (OR=1.61; 95% CI, 1.04-2.51) than the bottom 50%. Among 213 surveyed surgeons, extreme disease-specific factors had the largest utility (3 episodes in the last year, +74.4; percutaneous drain, + 69.4). Factors with strongest influence against surgery included 1 lifetime episode (-63.3), outpatient management (-54.9), and patient preference (-39.6). PRS was predicted to have high utility (+71). A PRS derived from a large national biobank was externally validated, and found to be associated with the incidence and severity of diverticulitis. Surgeons have clear guidance at clinical extremes, but demonstrate equipoise in intermediate scenarios. Surgeons are receptive to PRS, which may be most useful in marginal clinical situations. Given the current lack of accurate prognostication in recurrent diverticulitis, PRS may provide a novel approach for improving patient counseling and decision-making.

Mild forms of thrombotic microangiopathy in patients with advanced pancreatic cancer receiving gemcitabine and nab-paclitaxel. Thrombotic microangiopathy (TMA) is an uncommon complication that may occur in cancer patients usually as an expression of cancer-associated coagulopathy or due to drug-related toxicity. The clinical spectrum of TMA may vary from an incidental laboratory finding in cancer outpatients to potentially severe life-threatening clinical forms with organ involvement requiring prompt recognition and multidisciplinary evaluation. We present the clinical characteristics and outcomes of four patients with advanced pancreatic cancer with acute non-immune intravascular haemolysis compatible with microangiopathic acute haemolytic anaemia associated with mild thrombocytopenia during long-term gemcitabine and nab-paclitaxel treatment. Abnormal blood parameters (all four cases) and renal involvement (one case) were reversed with a conservative approach and chemotherapy discontinuation. One patient required a short hospitalization while the other three were managed as outpatients. The rapid reversibility of the blood abnormalities supported gemcitabine dose-related toxicity as the most likely aetiologic mechanism and demonstrates the current challenges in daily long-term cancer survivor care. Clinicians must take into account TMA in the differential diagnosis of acute anaemia with or without thrombocytopenia and organ damage, since adequate recognition and early treatment discontinuation allow effective outpatient management and favourable patient outcomes.

Orbicularis-Tarsus-Orbital Septum Fixation Technique in Asian Double-Eyelid Blepharoplasty: a Retrospective Study. The skin-tarsus-skin and orbicularis-levator fixation approaches are the 2 most applied techniques for double-eyelid blepharoplasty in China. However, both approaches have their own disadvantages. To achieve stable and dynamic upper eyelid creases, we take the merits of the 2 techniques. In this study, our orbicularis-tarsus-orbital septum fixation technique is introduced and evaluated. By transversely opening and turning down the anterior orbital septum, we created the septum roll anchored to the tarsus and the pretarsal muscular flap. As the motion transmitter, the roll could receive the pulling power of the levator aponeurosis transmitted to the tarsus and the septum respectively. With the help of the skin-septum roll-skin sutures, the roll passed on the pulling power directly to the pretarsal skin and thus the upper eyelid crease was formed. This study identified 105 Chinese patients (210 eyes) who underwent this technique in our department between September 2020 and May 2021. The follow-up ranged from 7 to 15 months. 90, 6, and 7 patients were satisfied, somewhat satisfied, and somewhat unsatisfied with the postoperative outcome, respectively. The satisfaction rate was 91.43% (96/105). Two patients were unsatisfied with the outcome, including 1 case of bilateral crease disappearance and 1 case of sunken upper eyelid. The orbicularis-tarsus-orbital septum fixation technique is safe and effective for double-eyelid blepharoplasty. This technique helps to form stable upper eyelid creases. Meanwhile, it is easy to achieve ideal curve and symmetry. By preserving the pretarsal tissue and using the orbital septum, sunken scar formation can be avoided.

Trends in Early and Late Mortality in Patients With Severe Acute Pancreatitis Admitted to ICUs: A Nationwide Cohort Study. To investigate national mortality trends over a 12-year period for patients with severe acute pancreatitis (SAP) admitted to Dutch ICUs. Additionally, an assessment of outcome in SAP was undertaken to differentiate between early (< 14 d of ICU admission) and late (> 14 d of ICU admission) mortality. Data from the Dutch National Intensive Care Evaluation and health insurance companies' databases were extracted. Outcomes included 14-day, ICU, hospital, and 1-year mortality. Mortality before and after 2010 was compared using mixed logistic regression and mixed Cox proportional-hazards models. Sensitivity analyses, excluding early mortality, were performed to assess trends in late mortality. Not applicable. Consecutive adult patients with SAP admitted to all 81 Dutch ICUs between 2007 and 2018. Not applicable. Among 4,160 patients treated in 81 ICUs, 14-day mortality was 17%, ICU mortality 17%, hospital mortality 23%, and 1-year mortality 33%. After 2010 in-hospital mortality adjusted for age, sex, modified Marshall, and Acute Physiology and Chronic Health Evaluation III scores were lower (odds ratio [OR], 0.76; 95% CI, 0.61-0.94) than before 2010. There was no change in ICU and 1-year mortality. Sensitivity analyses excluding patients with early mortality demonstrated a decreased ICU mortality (OR, 0.45; 95% CI, 0.32-0.64), decreased in-hospital (OR, 0.48; 95% CI, 0.36-0.63), and decreased 1-year mortality (hazard ratio, 0.81; 95% CI, 0.68-0.96) after 2010 compared with 2007-2010. Over the 12-year period examined, mortality in patients with SAP admitted to Dutch ICUs did not change, although after 2010 late mortality decreased. Novel therapies should focus on preventing early mortality in SAP.

Cranioplasty for Skull Defects With Polypropylene Abdominal Wall Mesh. Cranioplasty is a well-established common surgery in the practice of neurosurgery and craniofacial surgery. In young patients, complete skull defect closure by bone splitting may be troublesome due to the difficulty to obtain enough bone area. In such cases, sometimes the authors need to use allografts, which may not be widely available in rural practice. In this study, the authors present the series of cranioplasty with polypropylene mesh, which is widely used in abdominal wall closure. Nine patients with depressed compound skull fracture were treated by performing this technique. Selection criteria were: compound depressed skull fractures in which bones were fragmented in a way not able to be reconstructed with and leaving a skull defect, small-sized or relatively medium-sized skull defects, and skull defects not located on the sharp curvatures of the skull which needs firm bended meshes. All patients were male and their ages ranged between 8 months and 36 years.The skull bone defect was reconstructed with polypropylene abdominal wall mesh, which was sutured circumferentially with the galeal tissue. Skull defects were successfully treated in all patients. The follow-up period ranged from 4 to 13 months. One patient with a history of alcoholism and neglectance developed a wound infection after 3 weeks of surgery. This patient was treated successfully with intravenous antibiotics without the need to remove the mesh. There were no complications in the remaining 8 patients. Polypropylene mesh is a cheap and effective material for the reconstruction of small-sized or medium-sized skull defects. It can be a good alternative in rural practice and/or low economic communities, when other cranioplasty materials are not available.

Postoperative Serum Hyperamylasemia Adds Sequential Value to the Fistula Risk Score in Predicting Pancreatic Fistula after Pancreatoduodenectomy. To evaluate whether postoperative serum hyperamylasemia (POH), with drain fluid amylase (DFA) and C-reactive protein (CRP), improves the Fistula Risk Score (FRS) accuracy in assessing the risk of a postoperative pancreatic fistula (POPF). The FRS predicts POPF occurrence using intraoperative predictors with good accuracy but intrinsic limits. Outcomes of patients who underwent pancreaticoduodenectomies between 2016 and 2021 were evaluated across FRS-risk zones and POH occurrence. POH consists of serum amylase activity greater than the upper limit of normal (52 U/l), persisting within the first 48 hours postoperatively (postoperative day -POD- 1 and 2). Out of 905 pancreaticoduodenectomies, some FRS elements, namely soft pancreatic texture (odds ratio (OR) 11.6), pancreatic duct diameter (OR 0.80), high-risk pathologic diagnosis (OR 1.54), but not higher blood loss (OR 0.99), were associated with POH. POH was an independent predictor of POPF, which occurred in 46.8% of POH cases ( P <0.001). Once POH occurs, POPF incidence rises from 3.8% to 42.9%, 22.9% to 41.7%, and 48.9% to 59.2% in patients intraoperatively classified at low, moderate and high FRS risk, respectively. The predictive ability of multivariable models adding POD 1 drain fluid amylase, POD 1-2 POH and POD 3 C-reactive protein to the FRS showed progressively and significantly higher accuracy (AUC FRS=0.82, AUC FRS-DFA=0.85, AUC FRS-DFA-POH=0.87, AUC FRS-DFA-POH-CRP=0.90, DeLong always P <0.05). POPF risk assessment should follow a dynamic process. The stepwise retrieval of early, postoperative biological markers improves clinical risk stratification by increasing the granularity of POPF risk estimates and affords a possible therapeutic window before the actual morbidity of POPF occurs.

TIGIT-Fc Prolongs Corneal Allograft Survival in Mice by Upregulating TIGIT/CD226 Expression and the Proportion of Helios + Foxp3 + Treg Cells. Reduction of graft rejection remains key issue for supporting long-term graft retention after corneal transplantation. The relevance of Treg in reduction of corneal allografts rejection has been demonstrated. It has been recently reported that in addition to Foxp3, Helios is also considered to be a marker of activated Treg. Helios + Foxp3 + Treg are considered to be the true immunosuppressive Treg. TIGIT is an immunosuppressive costimulatory molecule that was found to be highly expressed on the surface of Helios + Foxp3 + Treg. In this study, we aimed to explore whether supplementing TIGIT would result in an expansion and activation of Helios + Foxp3 + Treg thus to mediate an immune tolerance following corneal transplantation by administering topically and systemically TIGIT-Fc treatment in murine models. TIGIT-Fc treatment significantly improved the survival of corneal allograft compared with the control group. TIGIT-Fc treatment increased TIGIT/CD226 expression, the proportion of Helios + Foxp3 + Treg cells and an enhanced ex vivo suppressive effect from peripheral lymph nodes isolated Treg cells. Furthermore, the expression of Helios in corneal grafts was upregulated, whereas expression of CD226 and production of aqueous interferon-γ and VEGF were reduced by TIGIT-Fc treatment. TIGIT-Fc treatment could specifically upregulate Helios + Foxp3 + Treg-mediated immune response after allogeneic corneal transplantation via TIGIT/CD226-CD155 pathway which improves the survival of allografts.

"No pain, no gain": The impact of autonomous sensory meridian response on pain perception. Autonomous sensory meridian response (ASMR) is a phenomenon characterised by a static-like tingling sensation spreading from the scalp and neck to the periphery in response to a variety of audio, visual, and tactile triggers resulting in a highly relaxed state and boosted positive affect. The limited literature on this phenomenon points to a potential of ASMR to alleviate pain. Emerging evidence also suggests that ASMR may be linked to increased sensory sensitivity more broadly. This study aimed to objectively address these claims by administering an algometer (measure of pain tolerance), and a visual analog scale (VAS) (measure of subjective pain sensitivity) to ASMR experiencers and controls at baseline, following an ASMR video, and a control video. Findings indicate that ASMR experiencers have a higher pain sensitivity than controls; however, there was no difference between the two groups in terms of pain tolerance. In addition, any potential analgesic properties associated with experiencing ASMR may reflect protective properties of ASMR buffering against the increased pain sensitivity among ASMR experiencers relative to controls.

Effect of the Use of Reinforced Stapling on the Occurrence of Pancreatic Fistula After Distal Pancreatectomy: Results of the REPLAY (REinforcement of the Pancreas in distaL pAncreatectomY) Multicenter Randomized Clinical Trial. The aim of the study was to evaluate the impact of the use of a reinforced stapler (RS) during distal pancreatectomy (DP) on postoperative outcomes. DP remains associated with significant postoperative morbidity owing to pancreatic fistula (PF). To date, there is no consensus on the management of the pancreatic stump. The use of an RS potentially represents a simple way to decrease the rate of PF. The REPLAY study (NCT03030170) is a prospective, multicenter, randomized study. Patients who underwent DP were randomized (1:1 ratio) in 2 groups for the use of a standard stapler (SS) or an RS to close remnant pancreatic parenchyma. The primary endpoint was the rate of overall PF. Secondary endpoints included severity of PF, length of hospital stay, overall morbidity, and rate of readmission for a PF within 90 days. Participants were blinded to the procedure actually carried out. A total of 199 were analyzed (SS, n=99; RS, n=100). One patient who did not undergo surgery was excluded. Baseline characteristics were comparable in both groups. The rate of overall PF was higher in RS group (SS: 67.7%, RS: 83%, P =0.0121), but the rate of clinically relevant PF was similar (SS: 11.1%, RS: 14%, P =0.5387). Mean length of total hospital stay, readmission for PF, postoperative morbidity, and mortality at 90 days were similar. The results of this randomized clinical trial did not favor the use of RS during DP to reduce the rate of PF.

A Novel Tumor Staging System Incorporating Tumor Regression Grade (TRG) With Lymph Node Status (ypN-Category) Results in Better Prognostication Than ypTNM Stage Groups After Neoadjuvant Therapy for Esophageal Squamous Cell Carcinoma. This study aims at constructing a staging system incorporating tumor regression grade and ypN-category (TRG-N) in patients with neoadjuvant therapy before esophagectomy. It is hypothesized that this would prognosticate better than the current American Joint Committee on Cancer (AJCC) postneoadjuvant therapy (ypTNM) stage groups. Conventional pathological T-category is defined by the depth of invasion, and may lose prognostic relevance after neoadjuvant therapy. TRG defines treatment response by the degree of tumor regression, and when combined with ypN-category may be more prognostic than AJCC postneoadjuvant therapy (ypTNM) stage groups. A training cohort of 210 patients with esophageal squamous cell carcinoma and who had had neoadjuvant therapy before esophagectomy were studied. A validation cohort comprised 107 patients from another hospital. Resected esophagi were assessed by ypT-category and TRG, the latter assigned according to the Becker 4-tier system. These categories were grouped with ypN-category into a TRG-N system. Patients' survival was compared between the current AJCC postneoadjuvant therapy (ypTNM) stage groups and this TRG-N system. In the training cohort, 5-year survival rates according to ypTNM stage I, II, IIIA, IIIB, and IVA were 53%, 39.4%, 47%, 18.3%, and 0%, respectively. For TRG-N stages I, II, III, and IV, the respective figures were 59.6%, 43.5%, 23.8%, and 15.6%. TRG-N stage showed better fit in survival than ypTNM stage groups, indicated by lower Akaike Information Criteria (AIC) and Bayesian Information Criterion values. Similar results were found in the validation cohort. Multivariate analysis showed that TRG-N stage ( P =0.02), age ( P =0.006), and sex ( P =0.005) were independent prognostic factors. TRG-N stage shows better prognostication than the AJCC postneoadjuvant therapy (ypTNM) stage groups.