Incidence, identification and antibiotic resistance of Salmonella spp. in the well waters of Tadla Plain, Morocco.

Concerns about challenges with water availability in the Tadla Plain region of Morocco have grown as a result of groundwater contamination brought on by human activity, climate change, and insufficient groundwater management. The objective of the study is to measure the number of resistant bacteria in the groundwater of Beni Moussa and Beni Aamir, as well as to evaluate the level of water pollution in this area. 200 samples were therefore gathered from 43 wells over the course of four seasonal campaigns in 2017 and 2018. Additionally, the samples were examined to determine whether Salmonella species were present and if they were resistant to the 16 antibiotics that were tested. Salmonella spp. have been identified in 31 isolated strains in total, accounting for 18.02% of all isolated strains. Data on antibiotic resistance show that 58.1% of Salmonella spp. strains are multidrug-resistant (MDR); 38.7% of Salmonella strains are tolerant to at least six antibiotics, 19.4% to at least nine antibiotics, 9.7% to four to seven antibiotics, 6.5% to at least eleven antibiotics, and the remaining 3.2% to up to twelve antibiotics. A considerable level of resistance to cefepime (61.29%), imipenem (54.84%), ceftazidime (45.16%), ofloxacin (70.97%), and ertapenem (74.19%) was found in the data. Consequently, it is important to monitor and regulate the growth of MDR in order to prevent the groundwater's quality from declining.

Pharmacokinetics and Exposure-Response Analyses to Support Dose Selection of Upadacitinib in Crohn's Disease.

Upadacitinib, a selective Janus kinase inhibitor, is the first orally administered therapy approved for the treatment of Crohn's disease (CD). This work characterized the pharmacokinetics of upadacitinib in CD patients and evaluated the relationships between upadacitinib steady-state plasma exposures and efficacy as well as safety parameters during the 12-week induction and the 52-week maintenance periods, to provide dosing recommendations for the treatment of CD. Upadacitinib pharmacokinetics in CD patients administered the extended-release formulation were consistent with patient populations in other approved indications. None of the evaluated CD-specific patient characteristics (e.g., disease location and prior gastrointestinal surgeries) had a meaningful impact on upadacitinib pharmacokinetics. Exposure-response analyses during 12-week induction treatment showed that response across all evaluated efficacy end points were approaching a plateau at median plasma exposures associated with 45 mg QD. Analyses for the maintenance period demonstrated that 30 mg QD is predicted to provide an additional 8% to 10% benefit for endoscopic response and endoscopic remission compared with 15 mg QD in patients who failed biologics. The analyses for safety showed a statistically significant relationship between increasing upadacitinib plasma exposures and the percentage of patients experiencing >2 g/dL decrease in hemoglobin from Baseline during induction and showed shallow relationships for serious infections and herpes zoster during the maintenance period. These results demonstrated adequate absorption of the extended-release formulation of upadacitinib in CD patients. The exposure-response analyses confirmed that 45 mg QD dose maximized efficacy as induction treatment and supported the selection of 15 mg QD or 30 mg QD as the maintenance doses.

RETRACTED: External pop-out versus classic technique for delivery of the fetal head during elective cesarean section: A randomized clinical trial.

This article has been retracted: please see Elsevier Policy on Article Withdrawal (https://www.elsevier.com/locate/withdrawalpolicy). This article has been retracted at the request of the Editor-in-Chief and the Journal's Ethics Committee. After post-publication investigation, issues related to the following were identified in the article: To facilitate a thorough examination and ensure the accuracy of the information reported in the article, the authors were asked for the raw data of the article. In the absence of an answer from the authors, a decision to retract the article was made in accordance with the journal's commitment to upholding the highest standards of scientific integrity and accuracy in published research.

Needle aspiration versus tube thoracostomy in patients with symptomatic primary spontaneous pneumothorax: an updated meta-analysis of randomized controlled trials.

Primary spontaneous pneumothorax (PSP) is an important disease commonly seen in young males. While incidentally diagnosed cases can be managed conservatively, symptomatic patients often necessitate intervention. Chest tube placement (tube thoracostomy) is commonly used, at least in the USA as a primary treatment modality, which requires hospitalization. On the other hand, needle aspiration (NA) has been widely adopted due to simplicity and reported efficacy and safety. No consensus is reached regarding superiority and/or preferred modality, with a lack of guidelines agreement. Therefore, we conducted an updated meta-analysis of randomized controlled trials comparing NA to tube thoracostomy in patients with symptomatic PSP. Prespecified outcomes were immediate success rate, 12-month recurrence rate, post intervention complications rate, and hospital length of stay. We identified and pooled data from six randomized trials, with a total of 759 patients and a median follow up of 12 months. Our analysis showed that NA and tube thoracostomy have similar immediate success rate and 12-month recurrence rate. We also found that NA has less complication rate, need for surgical intervention, and less hospital stays. In conclusion, our review showed that in symptomatic patients with PSP, NA is as effective as tube thoracostomy regarding immediate success rate and 12-month recurrence rate, with the added benefit of less complications rate and need for surgical intervention.

Mitigative Effects of l-Arginine and N-Acetyl Cysteine against Cisplatin-Induced Testicular Dysfunction and Toxicity through the Regulation of Antioxidant, Anti-inflammatory, and Antiapoptotic Markers: Role of miR-155 and miR-34c Expression.

Testicular dysfunction is a common adverse effect of cisplatin (CIS) administration as a chemotherapeutic drug. The current study has outlined the role of micro-RNAs (miR-155 and 34c) in CIS-induced testicular dysfunction and evaluated the protective effect of N-acetyl cysteine (NAC) and/or l-arginine (LA). Seven groups of Albino rats were used for this study. The control (C) group received physiological saline; the CIS group was injected CIS (7 mg/kg IP, once) on day 21 of the experiment; the NAC group was administered NAC (150 mg/kg intragastric, for 28 days); and the LA group was injected LA (50 mg/kg IP, for 28 days). NAC+CIS, LA+CIS, and NAC+LA+CIS groups received the above regime. CIS significantly reduced serum testosterone, LH, and FSH concentrations with decline of testicular enzyme activities. CIS caused significant elevation in testicular oxidative-stress biomarkers, inflammation-associated cytokines, and apoptosis markers, along with overexpression of miR-155 and low miR-34c expression. Additionally, marked testicular degenerative changes were observed in the examined histological section; a significant decrease in the expression of PCNA with significant increase in expressions of F4/80 and BAX was confirmed. The administration of NAC or LA upregulated testicular functions and improved histopathological and immunohistochemical changes as well as miRNA expression compared with the CIS-administered group. Rats receiving both NAC and LA showed a more significant ameliorative effect compared with groups receiving NAC or LA alone. In conclusion, NAC or LA showed an ameliorative effect against CIS-induced testicular toxicity and dysfunction through the regulation of antioxidant, anti-inflammatory, and antiapoptotic markers and via modulating miR-155 and miR-34c expression.

Hybrid controller with neural network PID/FOPID operations for two-link rigid robot manipulator based on the zebra optimization algorithm.

The performance of the robotic manipulator is negatively impacted by outside disturbances and uncertain parameters. The system's variables are also highly coupled, complex, and nonlinear, indicating that it is a multi-input, multi-output system. Therefore, it is necessary to develop a controller that can control the variables in the system in order to handle these complications. This work proposes six control structures based on neural networks (NNs) with proportional integral derivative (PID) and fractional-order PID (FOPID) controllers to operate a 2-link rigid robot manipulator (2-LRRM) for trajectory tracking. These are named as set-point-weighted PID (W-PID), set-point weighted FOPID (W-FOPID), recurrent neural network (RNN)-like PID (RNNPID), RNN-like FOPID (RNN-FOPID), NN+PID, and NN+FOPID controllers. The zebra optimization algorithm (ZOA) was used to adjust the parameters of the proposed controllers while reducing the integral-time-square error (ITSE). A new objective function was proposed for tuning to generate controllers with minimal chattering in the control signal. After implementing the proposed controller designs, a comparative robustness study was conducted among these controllers by altering the initial conditions, disturbances, and model uncertainties. The simulation results demonstrate that the NN+FOPID controller has the best trajectory tracking performance with the minimum ITSE and best robustness against changes in the initial states, external disturbances, and parameter uncertainties compared to the other controllers.

Serum calgranulin C as a non-invasive predictor of activity among inflammatory bowel disease.

Inflammatory bowel disease is a chronic immune-mediated disorder with a relapsing and remitting course. It leads to disabling gastrointestinal symptoms, low quality of life, and a significant burden for healthcare utilization and associated costs. Therefore, non-invasive biomarkers are needed for early diagnosis and follow up to avoid the complications of invasive diagnostic procedures. Calgranulin C is a calcium binding protein with proinflammatory properties. The aim of this study was to evaluate the role of serum calgranulin C as a non-invasive biomarker for diagnosis and prediction of activity in comparison to different biomarkers and endoscopic activity scores in inflammatory bowel disease. The study included 80 inflammatory bowel disease patients (50 Ulcerative colitis and 30 Chron's patients) and 20 normal controls. Complete blood picture, C-reactive protein, erythrocyte sedimentation rate, fecal calprotectin and serum calgranulin C were measured. Colonoscopies with histopathological examination were done and different activity scoring systems assessed. Among ulcerative colitis group, serum calgranulin C was statistically significantly higher in comparison to control group [723.640±529.055 ng/ml versus 80.850±24.416 ng/ml]. Depending on the American college of gastroenterology ulcerative colitis activity index, fecal calprotectin and serum calgranulin C were statistically significantly higher among moderate to severe ulcerative colitis than those with mild activity and those in remission (p < 0.001, for both). Regarding Crohn's disease group, serum calgranulin C was statistically significantly higher in comparison to control group [759.233±797.963 ng/ml versus 80.850±24.416 ng/mL]. Depending on Crohn's disease activity index, both serum calgranulin C and fecal calprotectin were statistically significantly higher among active disease than those in remission (p < 0.001, for both). In conclusion, serum calgranulin C could be used as a non-invasive marker to predict activity and severity and to ensure remission among inflammatory bowel disease patients.

Quality of different obturation techniques to fill perforating internal root resorption: a micro-computed tomographic study.

BACKGROUND: This study aimed to assess the quality of various obturation techniques to fill perforation caused by internal root resorption using Micro-computed Tomography. METHODS: Cone-beam computed tomography images of a maxillary central incisor tooth with perforating internal resorptive defect were used to create a 3D printed model of the affected tooth. The replicas were divided into four groups based on the obturation technique used. The techniques included Group 1: a polydimethylsiloxane-based sealer (GuttaFlow-2) with gutta-percha. Group 2: same as Group 1 except for using a pre-mixed Bioceramic-based sealer (NeoSEALER Flo). Group 3: the defect was filled entirely using the NeoSealer Flo Bioceramic-based sealer. Group 4: the samples were obturated using the warm vertical compaction technique with a resin-based sealer (ADSeal). The resin models were then scanned a micro-computed scanner to evaluate the percentage of voids in each group. RESULTS: The results showed that NeoSEALER Flo groups had significantly the highest volume of voids while GuttaFlow-2 and warm vertical compaction groups had the lowest void volume. CONCLUSIONS: GuttaFlow-2 and warm vertical compaction techniques performed best in filling the internal resorptive defect.

Sustainable utilization of Fe3O4-modified activated lignite for aqueous phosphate removal and ANN modeling.

Lignites are widely available and cost-effective in many countries. Sustainable methods for their utilization drive innovation, potentially advancing environmental sustainability and resource efficiency. In the present study, Fe3O4 (∼25.1 nm) supported on KOH-activated lignite (A-L) displayed 8 times higher phosphate removal than pristine A-L (67.6 mg/g vs. 8.5 mg/g at pH 5, 50 mg of absorbent in 25 mL of 1500 ppm [phosphate]), owing to its abundant Fe3O4 (10 wt.% of Fe) nanoparticle content. The removal occurred within ∼2 hours, following a pseudo-second-order kinetic model. Across pH levels ranging from 5.0 to 9.0, Fe3O4-A-L's phosphate removal occurs via both chemisorption and precipitation, as evident by kinetic, pH, and XPS analyses. The phosphate adsorption fits better with the Freundlich isotherm. The combined benefits of facile recovery, rapid phosphate uptake, straightforward regeneration, and attractive post-adsorption benefits (e.g., possibly use as a Fe, P-rich fertilizer) make magnetic Fe3O4-A-L a promising candidate for real-world applications. Artificial Neural Network (ANN) modeling indicates an excellent accuracy (R2 = 0.99) in predicting the amount of phosphate removed by Fe3O4-A-L. Sensitivity analysis revealed both temperature and initial concentration as the most influencing factors. Leveraging lignite in environmentally friendly applications not only addresses immediate challenges but also aligns with sustainability goals. The study clearly articulates the potential benefits of utilizing lignite for sustainable phosphate removal and recovery, offering avenues for mitigating environmental concerns while utilizing resources efficiently.

Injectable shear-thinning hydrogels promote oligodendrocyte progenitor cell survival and remyelination in the central nervous system.

Cell therapy for the treatment of demyelinating diseases such as multiple sclerosis is hampered by poor survival of donor oligodendrocyte cell preparations, resulting in limited therapeutic outcomes. Excessive cell death leads to the release of intracellular alloantigens, which likely exacerbate local inflammation and may predispose the graft to eventual rejection. Here, we engineered innovative cell-instructive shear-thinning hydrogels (STHs) with tunable viscoelasticity and bioactivity for minimally invasive delivery of primary human oligodendrocyte progenitor cells (hOPCs) to the brain of a shiverer/rag2 mouse, a model of congenital hypomyelinating disease. The STHs enabled immobilization of prosurvival signals, including a recombinantly designed bidomain peptide and platelet-derived growth factor. Notably, STHs reduced the death rate of hOPCs significantly, promoted the production of myelinating oligodendrocytes, and enhanced myelination of the mouse brain 12 weeks post-implantation. Our results demonstrate the potential of STHs loaded with biological cues to improve cell therapies for the treatment of devastating myelopathies.

Bariatric surgery in inflammatory bowel disease: a comparative analysis of 450,000 patients.

BACKGROUND: Studies were conducted to investigate the outcomes of bariatric surgery (BS) among inflammatory bowel disease (IBD) patients. OBJECTIVES: We aimed to analyze previous literature, comparing the outcomes of BS between IBD and non-IBD patients. SETTING: Not applicable. METHODS: PubMed, Scopus, and Web of Science were searched on 25/9/2023 for comparative studies on outcomes of BS in IBD patients. RevMan Software v5.4 was used to conduct the analysis. RESULTS: Our analysis revealed an insignificant difference in the change of body mass index (BMI) at 1-year post-BS between IBD and non-IBD patients. IBD patients had a higher risk of acute renal failure, hemorrhage, and readmission following BS (RR: 2.16, 95% CI: 1.55-3, RR: 1.57, 95% CI: 1.22-2.04, RR: 1.56, 95% CI: 1.17-2.08, respectively). No significant difference was observed between both groups regarding wounds, leak/intra-abdominal infection, thromboembolic complications, and bowel obstruction. A higher incidence of postoperative complications was seen among IBD patients undergoing RYGB compared with SG (RR: 2.21, 95% CI: 1.43-3.41). There was a significant decline in steroid use following BS in IBD patients (RR: .67, 95% CI: .53-.84). Comparison between UC and Crohn's disease (CD) revealed insignificant differences in treatment escalation or de-escalation. Both IBD and non-IBD patients had similar lengths of hospitalization. CONCLUSIONS: BS is equally effective in IBD and non-IBD patients in terms of weight loss at 1-year follow-up. Nevertheless, IBD patients are at a higher risk of postoperative complications, micronutrient deficiency, and readmission. Both UC and CD reported a decline in steroid use following surgery without a preferential advantage to a particular IBD sub-type.

Low dose insulin infusion versus the standard dose in children with diabetic ketoacidosis: a meta-analysis.

Aim: This systematic review aims to consolidate findings from current clinical trials that compare the effectiveness of insulin infusion at 0.05 IU/kg/h versus 0.1 IU/kg/h in managing pediatric diabetic ketoacidosis. Methods: We searched several databases, including PubMed, Embase, Scopus, Cochrane Central and Web of Science. Our primary outcomes were time to reach blood glucose ≤250 mg/dl and time to resolution of acidosis. Secondary outcomes included rate of blood glucose decrease per hour, incidence of hypoglycemia, hypokalemia, treatment failure, and cerebral edema. Results & conclusion: The present study establishes that a low insulin dose exhibits comparable efficacy to the standard dosage for managing pediatric patients suffering from diabetic ketoacidosis, with a lower incidence of complications.

When kids with type 1 Diabetes (T1DM) face a serious complication called Diabetic Ketoacidosis (DKA), it becomes a life-threatening situation. This condition, responsible for significant mortality, involves high blood sugar, ketone buildup and acidity. Our study delves into a critical aspect of DKA treatment-finding the right insulin dose. By pooling the studies on this point, we discovered that using a lower insulin dose is just as effective as the standard dose in managing DKA in children, with fewer complications. This insight is crucial for improving the care and outcomes for young patients dealing with this challenging condition.

Efficacy and Safety of Upadacitinib or Elsubrutinib Alone or in Combination for Systemic Lupus Erythematosus: A Phase 2 Randomized Controlled Trial.

OBJECTIVE: The 48-week, phase 2 SLEek study (NCT03978520) evaluated the efficacy and safety of upadacitinib (Janus kinase inhibitor) and elsubrutinib (Bruton's tyrosine kinase inhibitor) alone or in combination (ABBV-599) in adults with moderately to severely active systemic lupus erythematosus (SLE). METHODS: Patients were randomized 1:1:1:1:1 to once-daily (QD) ABBV-599 high dose (HD; elsubrutinib 60mg + upadacitinib 30mg), ABBV-599 low dose (LD; elsubrutinib 60mg + upadacitinib 15mg), elsubrutinib 60mg, upadacitinib 30mg, or placebo. The primary endpoint was the proportion of patients achieving both SLE Responder Index-4 (SRI-4) and glucocorticoid dose ≤10mg QD at week 24. Additional assessments through week 48 included British Isles Lupus Assessment Group-based Composite Lupus Assessment (BICLA) and Lupus Low Disease Activity State (LLDAS) responses, number of flares, time to first flare, and adverse events. RESULTS: The study enrolled 341 patients. The ABBV-599LD and elsubrutinib arms were discontinued after a planned interim analysis showed lack of efficacy (no safety concerns). More patients achieved the primary endpoint with upadacitinib (54.8%; P=0.028) and ABBV-599HD (48.5%; P=0.081) versus placebo (37.3%). SRI-4, BICLA, and LLDAS response rates were higher for both upadacitinib and ABBV-599HD versus placebo at weeks 24 and 48. Flares were reduced and time to first flare through week 48 was substantially delayed with both upadacitinib and ABBV-599HD versus placebo. No new safety signals were observed beyond those previously reported for upadacitinib or elsubrutinib. CONCLUSIONS: Upadacitinib 30mg alone or in combination with elsubrutinib (ABBV-599HD) demonstrated significant improvements in SLE disease activity, reduced flares and were well tolerated through 48 weeks.

Veterinary Drug Residues in the Food Chain as an Emerging Public Health Threat: Sources, Analytical Methods, Health Impacts, and Preventive Measures.

Veterinary medications are necessary for both contemporary animal husbandry and food production, but their residues can linger in foods obtained from animals and pose a dangerous human risk. In this review, we aim to highlight the sources, occurrence, human exposure pathways, and human health effects of drug residues in food-animal products. Following the usage of veterinary medications, pharmacologically active compounds known as drug residues can be found in food, the environment, or animals. They can cause major health concerns to people, including antibiotic resistance development, the development of cancer, teratogenic effects, hypersensitivity, and disruption of normal intestinal flora. Drug residues in animal products can originate from variety of sources, including water or food contamination, extra-label drug use, and ignoring drug withdrawal periods. This review also examines how humans can be exposed to drug residues through drinking water, food, air, and dust, and discusses various analytical techniques for identifying these residues in food. Furthermore, we suggest some potential solutions to prevent or reduce drug residues in animal products and human exposure pathways, such as implementing withdrawal periods, monitoring programs, education campaigns, and new technologies that are crucial for safeguarding public health. This review underscores the urgency of addressing veterinary drug residues as a significant and emerging public health threat, calling for collaborative efforts from researchers, policymakers, and industry stakeholders to develop sustainable solutions that ensure the safety of the global food supply chain.

Analysis of MiR-20b, MIR-197 markers for differentiation between forensic body fluids encountered in sexual assault cases.

Identifying body fluids can be a critical clue that aids in reconstructing the crime scene. Semen and vaginal fluid identification is crucial, especially in cases of sexual assault. The majority of forensic studies focused on identifying normal body fluids and neglected the expression variation of semen in pathology. To differentiate between vaginal fluids, fertile and infertile semen samples (oligospermia and azoospermia) using miR 20b and miR197. A total of 48 body fluid samples, divided as 16 vaginal fluids, 16 fertile semen, and 16 infertile semen samples (8 with oligospermia and 8 with azoospermia), were collected, and the expression levels of miR-20b and miR-197 were detected by the SYBR Green real-time quantitative PCR technique. Our results showed significant different expression of these miRNAs in normal semen compared to vaginal and infertile semen. Moreover, we designed a model based on Fisher's discriminant function to forecast the group affiliations of unidentified samples. With three novel equations, we were able to accurately distinguish between semen and vaginal fluid, fertile and infertile semen, and oligospermia and azoospermia semen samples with validation accuracy of 81.3%, 100%, and 100%, respectively. MiR-20b and miR-197 expression levels are efficient and appropriate markers to distinguish semen from vaginal fluid and to differentiate between fertile and infertile semen samples. However, the present study is a preliminary study based on clinical samples, and the potential role of these markers in differentiating real crime scene samples is still unknown, so we recommend further research to investigate these markers expression while using forensic samples.

Blood-stage malaria vaccine candidate RH5.1/Matrix-M in healthy Tanzanian adults and children; an open-label, non-randomised, first-in-human, single-centre, phase 1b trial.

BACKGROUND: A blood-stage Plasmodium falciparum malaria vaccine would provide a second line of defence to complement partially effective or waning immunity conferred by the approved pre-erythrocytic vaccines. RH5.1 is a soluble protein vaccine candidate for blood-stage P falciparum, formulated with Matrix-M adjuvant to assess safety and immunogenicity in a malaria-endemic adult and paediatric population for the first time. METHODS: We did a non-randomised, phase 1b, single-centre, dose-escalation, age de-escalation, first-in-human trial of RH5.1/Matrix-M in Bagamoyo, Tanzania. We recruited healthy adults (aged 18-45 years) and children (aged 5-17 months) to receive the RH5.1/Matrix-M vaccine candidate in the following three-dose regimens: 10 µg RH5.1 at 0, 1, and 2 months (Adults 10M), and the higher dose of 50 µg RH5.1 at 0 and 1 month and 10 µg RH5.1 at 6 months (delayed-fractional third dose regimen; Adults DFx). Children received either 10 µg RH5.1 at 0, 1, and 2 months (Children 10M) or 10 µg RH5.1 at 0, 1, and 6 months (delayed third dose regimen; Children 10D), and were recruited in parallel, followed by children who received the dose-escalation regimen (Children DFx) and children with higher malaria pre-exposure who also received the dose-escalation regimen (High Children DFx). All RH5.1 doses were formulated with 50 µg Matrix-M adjuvant. Primary outcomes for vaccine safety were solicited and unsolicited adverse events after each vaccination, along with any serious adverse events during the study period. The secondary outcome measures for immunogenicity were the concentration and avidity of anti-RH5.1 serum IgG antibodies and their percentage growth inhibition activity (GIA) in vitro, as well as cellular immunogenicity to RH5.1. All participants receiving at least one dose of vaccine were included in the primary analyses. This trial is registered at ClinicalTrials.gov, NCT04318002, and is now complete. FINDINGS: Between Jan 25, 2021, and April 15, 2021, we recruited 12 adults (six [50%] in the Adults 10M group and six [50%] in the Adults DFx group) and 48 children (12 each in the Children 10M, Children 10D, Children DFx, and High Children DFx groups). 57 (95%) of 60 participants completed the vaccination series and 55 (92%) completed 22 months of follow-up following the third vaccination. Vaccinations were well-tolerated across both age groups. There were five serious adverse events involving four child participants during the trial, none of which were deemed related to vaccination. RH5-specific T cell and serum IgG antibody responses were induced by vaccination and purified total IgG showed in vitro GIA against P falciparum. We found similar functional quality (ie, GIA per µg RH5-specific IgG) across all age groups and dosing regimens at 14 days after the final vaccination; the concentration of RH5.1-specific polyclonal IgG required to give 50% GIA was 14·3 µg/mL (95% CI 13·4-15·2). 11 children were vaccinated with the delayed third dose regimen and showed the highest median anti-RH5 serum IgG concentration 14 days following the third vaccination (723 µg/mL [IQR 511-1000]), resulting in all 11 who received the full series showing greater than 60% GIA following dilution of total IgG to 2·5 mg/mL (median 88% [IQR 81-94]). INTERPRETATION: The RH5.1/Matrix-M vaccine candidate shows an acceptable safety and reactogenicity profile in both adults and 5-17-month-old children residing in a malaria-endemic area, with all children in the delayed third dose regimen reaching a level of GIA previously associated with protective outcome against blood-stage P falciparum challenge in non-human primates. These data support onward efficacy assessment of this vaccine candidate against clinical malaria in young African children. FUNDING: The European and Developing Countries Clinical Trials Partnership; the UK Medical Research Council; the UK Department for International Development; the National Institute for Health and Care Research Oxford Biomedical Research Centre; the Division of Intramural Research, National Institute of Allergy and Infectious Diseases; the US Agency for International Development; and the Wellcome Trust.

Selective and Sensitive Detection of Fe3+ Ions Using a Red-Emissive Fluorescent Probe Based on Triphenylamine and Perylene-Linked Conjugated Microporous Polymer.

The Expansion of modern industry underscores the urgent need to address heavy metal pollution, which is a threat to human-health and environment. Efforts are underwent to develop precise technologies for detecting heavy metal ions (M+-ion). One promising approach involves the use of Conjugated Microporous Polymers (CMPs) modified with Triphenylamine (TPA) anderylene (Peryl), known as TPA-Peryl-CMP, which emits strong refluorescence. Various analytical techniques, such as Brunauer-Emmett-Teller analysis, Fourier transform infrared (FTIR) spectroscopy, nuclear magnetic resonance (NMR) spectroscopy, and thermogravimetric analysis (TGA), are utilized to characterize the synthesized TPA-Peryl-CMP and understand its functional properties. In addition to its remarkable fluorescence behavior, TPA-Peryl-CMP shows promise as a sensor for Fe3+ ions using a turn-off strategy. Due to its exceptional stability and robust π-electron system, this platform demonstrates remarkable sensitivity and selectivity, significantly improving detection capabilities for specific analytes. Detailed procedures related to the mechanism for detecting Fe3+ ions are outlined for sensing Fe3+ ions, revealing a notably strong linear correlation within the concentration range of 0-3 µM, with a correlation coefficient of 0.9936 and the Limit of detection (LOD) 20 nM. It is anticipated that development of such a kind of TPA-Peryl-CMP will observe broader applications in detecting various analytes related to environmental and biological systems.

Outcomes of an All-Soft Tissue Fixation Technique for Reconstruction of the Medial Patellofemoral Complex Using Double-Bundle Quadriceps Tendon Autograft for Recurrent Patellar Dislocation in Skeletally Immature Patients.

Background: Patellar fracture, femoral physis injury, and recurrent instability are concerning complications in medial patellofemoral ligament (MPFL) reconstruction (MPFLR) techniques for recurrent patellar dislocation in children and adolescents. Purpose: To evaluate the outcomes of an anatomic all-soft tissue fixation technique for reconstruction of the medial patellofemoral complex (MPFC) using a double-bundle quadriceps tendon (QT) autograft for recurrent patellar dislocation in skeletally immature patients. Study Design: Case series; Level of evidence, 4. Methods: This retrospective study involved 24 skeletally immature patients (24 knees; 16 women and 8 men; age range, 9.5-15 years) with recurrent patellar dislocation who underwent MPFC reconstruction using a double-bundle QT autograft between September 2018 and January 2021. Only soft tissue suture fixation was used on the femoral and patellar sides of the 2 bundles of the QT. Radiographs, computed tomography, and magnetic resonance imaging were used to evaluate physeal status, lower limb alignment, patellar height and tilt, trochlear morphology, tibial tubercle-trochlear groove distance, and any associated knee pathology. Functional outcomes were assessed with the Kujala score, the visual analog scale (VAS) for pain, and the grading system of Insall et al.22. Results: The mean follow-up time was 40 ± 9.6 months (range, 28-56 months). At the final follow-up, the Kujala and VAS pain scores showed a significant improvement versus preoperative scores (P < .001), and the passive lateral patellar glide showed a significant reduction (P < .001). All patients had negative apprehension and J signs. Of the 24 patients, 23 regained full range of motion, while 1 patient had a knee flexion deficit. The patellar tilt angle improved significantly at the final follow-up (P < .001). There was no patellar fracture, femoral physis injury, or recurrence of patellar dislocation. According to the grading system of Insall et al, the results were excellent in 15 knees (62.5%), good in 8 knees (33.3%), fair in 1 knee (4.2%), and no knees showed poor results. Conclusion: Reconstruction of the MPFC using a double-bundle QT autograft with an all-soft tissue fixation technique was an effective method for treating patellar instability in skeletally immature patients.

Cedirogant in adults with psoriasis: a phase 2, randomized, placebo-controlled clinical trial.

BACKGROUND: Dysregulated interleukin (IL)-17/IL-23 signaling contributes to psoriasis pathogenesis. Cedirogant is an inverse agonist of retinoic acid-related orphan receptor gamma thymus (RORγt), a key transcription factor responsible for IL-17 synthesis and a regulator of the T helper 17 cell lineage program. OBJECTIVE: To evaluate the efficacy and safety of cedirogant to treat moderate-to-severe psoriasis. METHODS: In this phase 2b, multicenter, double-blind, 16-week study (NCT05044234), adults aged 18-65 years were randomized 1:1:1:1 to once-daily oral cedirogant 75 mg, 150 mg, 375 mg, or placebo. Assessments included ≥50%/75%/90%/100% improvement from baseline in Psoriasis Area and Severity Index (PASI 50/75/90/100), static Physician Global Assessment 0/1, Psoriasis Symptoms Scale 0, and improvements in itch, adverse events (AEs), pharmacokinetics, and IL-17A/F levels. Efficacy results based on observed cases were summarized descriptively. RESULTS: Of 156 enrolled patients, most were male (70.5%); 39 patients were randomized to each treatment. Only 47 patients completed the study; the study was terminated early due to preclinical findings. At week 16, PASI 75 achievement rates (primary endpoint) were 28.6%, 7.7%, and 41.7% in the cedirogant 75 mg, 150 mg, and 375 mg groups, respectively, and 0% in the placebo group. AE rates were similar in the cedirogant 75 mg, 150 mg, and placebo groups and higher in the cedirogant 375-mg group; most AEs were mild or moderate. CONCLUSIONS: Patients with psoriasis who received cedirogant showed PASI improvement and cedirogant was generally well tolerated. Results should be interpreted in the context of early study termination. Cedirogant development has been discontinued.