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Kidney transplant recipients are at an increased risk of hospitalisation and death from SARS-CoV-2 infection, and standard two-dose vaccination schedules are typically inadequate to generate protective immunity. Gut dysbiosis, which is common among kidney transplant recipients and known to effect systemic immunity, may be a contributing factor to a lack of vaccine immunogenicity in this at-risk cohort. The gut microbiota modulates vaccine responses, with the production of immunomodulatory short-chain fatty acids by bacteria such as Bifidobacterium associated with heightened vaccine responses in both observational and experimental studies. As SCFA-producing populations in the gut microbiota are enhanced by diets rich in non-digestible fibre, dietary supplementation with prebiotic fibre emerges as a potential adjuvant strategy to correct dysbiosis and improve vaccine-induced immunity. In a randomised, double-bind, placebo-controlled trial of 72 kidney transplant recipients, we found dietary supplementation with prebiotic inulin for 4 weeks before and after a third SARS-CoV2 mRNA vaccine to be feasible, tolerable, and safe. Inulin supplementation resulted in an increase in gut Bifidobacterium, as determined by 16S RNA sequencing, but did not increase in vitro neutralisation of live SARS-CoV-2 virus at 4 weeks following a third vaccination. Dietary fibre supplementation is a feasible strategy with the potential to enhance vaccine-induced immunity and warrants further investigation.

Let's face it, a robust infrastructure can be extremely expensive and complex. And while businesses usually understand their own organisation and market better than any consultant, they often lack the internal expertise, dedicated resources and network access to plan and manage their own e-business infrastructure successfully. Now, outsourcing a company's e-business infrastructure at a time when it is an increasingly important part of the business process is not something to be entered into lightly. An \"end-to-end\" e-business infrastructure is no longer the desktops at one end and the servers at the other - all within the same enterprise. It is now an critical lifeline that stretches from that supplier you have in Singapore to your corporate headquarters in New York to the customer in Beijing. The multi-faceted discipline of managing e-business infrastructure is complex, resource-intensive, specialised, and dynamic. More and more companies will come to the conclusion that their senior management's time is better spent growing their own business and leaving infrastructure management to the experts. This in turn will provide service providers with the economies of scale they need to provide higher levels of service at lower costs to the customer.

Background Arthrodesis serves as the traditional therapeutic approach for advanced distal interphalangeal joint (DIPJ) arthritis. However, the conventional technique may prove insufficient when the excision of pronounced volar and lateral spurs is required. To address this, we innovated the 'smile incision with reverse shotgun approach'. This method enhances joint exposure and yields superior cosmetic results by extending the transverse skin incision over the DIPJ and cleaving the accessory collateral ligament, thereby improving access to the volar and lateral joint margins. This article meticulously elucidates the surgical procedure and presents preliminary results of its implementation. Method The clinical data of 22 consecutive patients (36 fingers) who received DIPJ arthrodesis by this procedure during March 2018 to October 2022, with a mean follow-up period of 9.8 months, were reviewed. Patients’ demographics, union rate, complications, radiographic findings, as well as visual analogue scale (VAS) for pain and satisfaction, were collected and analyzed. Results Thirty-five of 36 fingers achieved uneventful bony union (97.2%). The average VAS for pain and satisfaction as well as he coronal plane deviation of DIPJ significantly improved after the operation (all, P < 0.05). No skin necrosis, nail deformity, or infection were observed during the follow-up period. Conclusion The smile incision and reverse shotgun approach provided excellent DIPJ exposure, high union rate, and cosmetic appearance for DIPJ arthrodesis surgery. This technique may be a good surgical option for DIPJ arthrodesis when more volar part joint preparation and more volar implant insertion sites are necessary.

Negative and positive emotions are the risk and protective factors for the cause and prognosis of hypertension. This study aimed to use five photoplethysmography (PPG) waveform indices and affective computing (AC) to discriminate the emotional states in patients with hypertension. Forty-three patients with essential hypertension were measured for blood pressure and PPG signals under baseline and four emotional conditions (neutral, anger, happiness, and sadness), and the PPG signals were transformed into the mean standard deviation of five PPG waveform indices. A support vector machine was used as a classifier. The performance of the classifier was verified by using resubstitution and six-fold cross-validation (CV) methods. Feature selectors, including full search and genetic algorithm (GA), were used to select effective feature combinations. Traditional statistical analyses only differentiated between the emotional states and baseline, whereas AC achieved 100% accuracy in distinguishing between the emotional states and baseline by using the resubstitution method. AC showed high accuracy rates when used with 10 waveform features in distinguishing the records into two, three, and four classes by applying a six-fold CV. The GA feature selector further boosted the accuracy to 78.97%, 74.22%, and 67.35% in two-, three-, and four-class differentiation, respectively. The proposed AC achieved high accuracy in categorizing PPG records into distinct emotional states with features extracted from only five waveform indices. The results demonstrated the effectiveness of the five indices and the proposed AC in patients with hypertension.

Imbalances in gut microbiota composition are linked to hypertension, host metabolic abnormalities, systemic inflammation, and other conditions. In the present study, we examined the changes of gut microbiota in women with early-onset preeclampsia (PE) and in normotensive, uncomplicated pregnant women during late pregnancy and at 1 and 6 weeks postpartum. Gut microbiota profiles of women with PE and healthy pregnant women in the third trimester and at 1 and 6 weeks postpartum were assessed by 16S rRNA gene amplicon sequencing. Plasma levels of interleukin-6 (IL-6), intestinal fatty acid-binding protein (I-FABP), zonulin, and lipopolysaccharide (LPS) were measured in the third trimesters. At the genus level, 8 bacterial genera were significantly enriched in the antepartum samples of PE patients compared to healthy controls, of which , and represented the major variances in PE microbiomes. Conversely, 5 genera, including , and , were significantly depleted in antepartum PE samples. Maternal blood pressure and liver enzyme levels were positively correlated to the PE-enriched genera such as , and , while the fetal features (e.g., Apgar score and newborn birth weight) were positively correlated with PE-depleted genera and negatively correlated with PE-enriched genera. Moreover, maternal blood IL-6 level was positively associated with gut and , whereas LPS level was negatively associated with . In terms of postpartum women, both the gut microbial composition and the PE-associated microbial alterations were highly consistent with those of the antepartum women. PE diagnosed in the third trimester of pregnancy is associated with a disrupted gut microbiota composition compared with uncomplicated pregnant women, which are associated with maternal clinical features (blood pressure level and liver dysfunction) and newborn birth weight. Moreover, these antepartum alterations in gut microbiota persisted 6 weeks postpartum.

Postoperative delirium (POD) is a common postoperative complication, and the potential relationship between cigarette smoking and POD is still unclear. The current study evaluated the relationship between preoperative smoking status in patients suffering from osteoarthritic pain and POD after total knee arthroplasty (TKA). A total of 254 patients who had undergone unilateral TKA were enrolled between November 2021 and December 2022, with no gender limitation. Preoperatively, patients' visual analog scale (VAS) scores at rest and during movement, hospital anxiety and depression (HAD) scores, pain catastrophizing scale (PCS) scores and smoking status were collected. The primary outcome was the incidence of POD, which was evaluated by the confusion assessment method (CAM). A total of 188 patients had complete datasets for final analysis. POD was diagnosed in 41 of 188 patients (21.8%) who had complete data for analysis. The incidence of smoking was significantly higher in Group POD than in Group Non-POD (22 of 41 patients [54%] vs. 47 of 147 patients [32%], p < 0.05). The postoperative hospital stays were also longer than those of Group Non-POD (p < 0.001). Multiple logistic regression analysis showed that preoperative smoking (OR: 4.018, 95% CI: 1.158-13.947, p = 0.028) was a risk factor for the occurrence of POD in patients with TKA. The length of hospital stay was correlated with the occurrence of POD. Our findings suggest that patients who smoked preoperatively were at increased risk of developing POD following TKA.

Burn-induced neuromuscular dysfunction may contribute to long-term morbidity; therefore, it is imperative to develop novel treatments. The present study investigated whether erythropoietin (EPO) administration attenuates burn-induced motor neuron apoptosis and neuroinflammatory response. To validate our hypothesis, a third-degree hind paw burn rat model was developed by bringing the paw into contact with a metal surface at 75°C for 10 s. A total of 24 male Sprague-Dawley rats were randomly assigned to four groups: Group A, sham-control; Group B, burn-induced; Group C, burn + single EPO dose (5000 IU/kg i.p. at D0); and Group D, burn + daily EPO dosage (3000 IU/kg/day i.p. at D0-D6). Two treatment regimens were used to evaluate single versus multiple doses treatment effects. Before sacrifice, blood samples were collected for hematological parameter examination. The histological analyses of microglia activation, iNOS, and COX-2 in the spinal cord ventral horn were performed at week 1 post-burn. In addition, we examined autophagy changes by biomarkers of LC3B and ATG5. The expression of BCL-2, BAX, cleaved caspase-3, phospho-AKT, and mTOR was assessed simultaneously through Western blotting. EPO administration after burn injury attenuated neuroinflammation through various mechanisms, including the reduction of microglia activity as well as iNOS and COX-2 expression in the spinal cord ventral horn. In addition, the expression of phospho-AKT, mTOR and apoptotic indicators, such as BAX, BCL-2, and cleaved caspase-3, was modulated. Furthermore, the activity of burn-induced autophagy in the spinal cord ventral horn characterized by the expression of autophagic biomarkers, LC3B and ATG5, was reduced after EPO administration. The present results indicate that EPO inhibits the AKT-mTOR pathway to attenuate burn-induced motor neuron programmed cell death and microglia activation. EPO can modulate neuroinflammation and programmed cell death and may be a therapeutic candidate for neuroprotection.

Paratuberculosis a contagious and chronic disease in domestic and wild ruminants, is caused by Mycobacterium avium subspecies paratuberculosis (MAP). Typical clinical signs include intractable diarrhea, progressive emaciation, proliferative enteropathy, and mesenteric lymphadenitis. Paratuberculosis is endemic to many parts of the world and responsible for considerable economic losses. In this study, different types of paratuberculosis and MAP in sheep and goats were investigated in Inner Mongolia, a northern province in China contiguous with two countries and eight other provinces. A total of 4434 serum samples were collected from six cities in the western, central, and eastern regions of Inner Mongolia and analyzed using the ELISA test. In addition, tissue samples were collected from seven animals that were suspected to be infected with MAP. Finally, these tissues samples were analyzed by histopathological examination followed by polymerase chain reaction (PCR), IS1311 PCR-restriction enzyme analysis (PCR-REA), and a sequence analysis of five genes. Among all 4434 ruminant serum samples collected from the six cities in the western, central, and eastern regions of Inner Mongolia, 7.60% (337/4434) measured positive for the MAP antibody. The proportions of positive MAP antibody results for serum samples collected in the western, central, and eastern regions were 5.10% (105/2058), 6.63% (85/1282), and 13.44% (147/1094), respectively. For the seven suspected infected animals selected from the herd with the highest rate of positivity, the gross pathology and histopathology of the necropsied animals were found to be consistent with the pathological features of paratuberculosis. The PCR analysis further confirmed the diagnosis of paratuberculosis. The rest of the results demonstrated that herds of sheep and goats in Inner Mongolia were infected with both MAP type II and type III. To the best of our knowledge, this is the first study of the two subtypes of MAP strains in sheep and goats in Inner Mongolia.

Human embryonic stem cell-derived β cells (SC-β cells) hold great promise for treatment of diabetes, yet how to achieve functional maturation and protect them against metabolic stresses such as glucotoxicity and lipotoxicity remains elusive. Our single-cell RNA-seq analysis reveals that ZnT8 loss of function (LOF) accelerates the functional maturation of SC-β cells. As a result, ZnT8 LOF improves glucose-stimulated insulin secretion (GSIS) by releasing the negative feedback of zinc inhibition on insulin secretion. Furthermore, we demonstrate that ZnT8 LOF mutations endow SC-β cells with resistance to lipotoxicity/glucotoxicity-triggered cell death by alleviating endoplasmic reticulum (ER) stress through modulation of zinc levels. Importantly, transplantation of SC-β cells with ZnT8 LOF into mice with preexisting diabetes significantly improves glycemia restoration and glucose tolerance. These findings highlight the beneficial effect of ZnT8 LOF on the functional maturation and survival of SC-β cells that are useful as a potential source for cell replacement therapies. Immature function and fragility hinder application of hESC-derived β cells (SC-β cell) for diabetes cell therapy. Here, the authors identify ZnT8 as a gene editing target to enhance the insulin secretion and cell survival under metabolic stress by abolishing zinc transport in SC-β cells.