Choroid plexus enlargement correlates with periventricular pathology but not with disease activity in radiologically isolated syndrome.

BACKGROUND: Choroid plexus (ChP) enlargement is an emerging radiological biomarker in multiple sclerosis (MS). OBJECTIVES: This study aims to assess ChP volume in a large cohort of patients with radiologically isolated syndrome (RIS) versus healthy controls (HC) and explore its relationship with other brain volumes, disease activity, and biological markers. METHODS: RIS individuals were included retrospectively and compared with HC. ChPs were automatically segmented using an in-house automated algorithm and manually corrected. RESULTS: A total of 124 patients fulfilled the 2023 RIS criteria, and 55 HCs were included. We confirmed that ChPs are enlarged in RIS versus HC (mean (±SD) normalized ChP volume: 17.24 (±4.95) and 11.61 (±3.58), respectively, p < 0.001). Larger ChPs were associated with more periventricular lesions (ρ = 0.26; r2 = 0.27; p = 0.005 for the correlation with lesion volume, and ρ = 0.2; r2 = 0.21; p = 0.002 for the correlation with lesion number) and lower thalamic volume (ρ = -0.38; r2 = 0.44; p < 0.001), but not with lesions in other brain regions. Conversely, ChP volume did not correlate with biological markers. No significant difference in ChP volume was observed between subjects who presented or did not have a clinical event or between those with or without imaging disease activity. CONCLUSIONS: This study provides evidence that ChP volume is higher in RIS and is associated with measures reflecting periventricular pathology but does not correlate with biological, radiological, or clinical markers of disease activity.

Vanillin loaded-physically crosslinked PVA/chitosan/itaconic membranes for topical wound healing applications.

Vanillin loaded-physically crosslinked hydrogel membranes made of PVA/chitosan/itaconic acid (PVA-CS-IA) were prepared using freezing-thawing (F-T) cycle method. To ensure the entanglement of PVA-CS-IA chains, three F-T cycles were repeated. The polymeric chains entanglements were confirmed and characterized by different instrumental characterizations. Physicochemical properties for example, swelling ratio, mechanical characteristics, gel fraction percentage (GF%), hydrolytic degradation, and thermal stability of PVA-CS-IA membrane were discussed in detail. The findings showed that the swelling ratio, mechanical characteristics, and hydrolytic degradation of the crosslinked membranes enhanced with increasing CS-IA contents in membranes composition; however, GF% gradually declined with CS-IA content. Additionally, cell viability test using HFB-4 cell line and antimicrobial activity against Staphylococcus aureus and Escherichia coli were evaluated using MTT assay and the bacterium growth inhibition percentage method; respectively. Notably, with varying incubation durations and membrane concentrations, all examined constructed hydrogels showed significant cell survival percentages. The findings supported the notion that produced hydrogel membranes might be used in a professional setting as antibacterial dressings or biomaterials for quick wound healing rate.

Quality of care for chronic conditions: identifying specificities of quality aims based on scoping review and Delphi survey.

There is a growing need to implement high quality chronic care to address the global burden of chronic conditions. However, to our knowledge, there have been no systematic attempts to define and specify aims for chronic care quality. To address this gap, we conducted a scoping review and Delphi survey to establish and validate comprehensive specifications. The Institute of Medicine's (IOM) quality of care definition and aims were used as the foundation. We purposively selected articles from the scientific (n=48) and grey literature (n=26). We sought papers that acknowledged and unpacked the plurality of quality in chronic care and proposed or utilised frameworks, studied their implementation, or investigated at least two IOM quality care aims and implementation. Articles were analysed both deductively and inductively. The findings were validated through a Delphi survey involving 49 international chronic care experts with varied knowledge of, and experience in, low-and-middle-income countries. Considering the natural history of chronic conditions and the journey of a person with a chronic condition, we defined and identified the aims of chronic care quality. The six IOM aims apply with specific meanings. We identified a seventh aim, continuity, which relates to the issue of chronicity. The group endorsed our specifications and several participants gave contextualised interpretations and concrete examples. Chronic conditions pose specific challenges underscoring the relevance of tailoring quality of care aims. The next steps require a tailored definition and specific aims to improve, measure and assure the quality of chronic care.

Main findings: While previously defined aims of good-quality care may also apply to chronic care quality, the nature of chronic conditions and ensuing healthcare needs warrant specifications for good-quality chronic care.Added knowledge: Our proposed definition and specific aims are tailored to the natural history of chronic conditions, and can serve as a guide on determining what can be deemed as good-quality chronic care.Global health impact for policy and action: This work, developed to guide further work on designing purchasing instruments to improve quality of chronic care, particularly in low- and middle-income countries, may also be a source of inspiration for other interventions aiming at improving quality of chronic care.

Effectiveness of safety netting approaches for acutely ill children: a network meta-analysis.

BACKGROUND: Safety netting advice (SNA) can help in the management of acutely ill children. AIM: Assess the effectiveness of different SNA methods for acutely ill children on antibiotic prescription and consumption. DESIGN AND SETTING: Systematic review and network meta-analysis of randomised controlled trials, non-randomised trials of interventions, and controlled before-after studies in ambulatory care. METHOD: We searched MEDLINE, Embase, Web-Of-Science Core Collection, and Cochrane Central Register of Controlled Trials (22 January 2024). We assessed the risk of bias (RoB) with the Cochrane Tool 2, Revised Cochrane Tool for Cluster-Randomised Trials, and ROBINS-I tool. Certainty of evidence was assessed using the CINeMA approach. We performed sensitivity analyses and network meta-regression. RESULTS: We included 30 studies (20 interventions). Compared to usual care, paper SNA may reduce antibiotic prescribing (OR=0.66 (95%CI: 0.53-0.85), I²=92%, very low certainty; 3 studies, 35,988 participants), especially when combined with oral SNA (OR=0.40 (95%CI: 0.08-2.00), P-score: 0.86), antibiotic consumption (OR=0.39 (95%CI: 0.27-0.58), low RoB; 1 study, 509 participants), and return visits (OR=0.74 , 95%CI 0.63-0.87). Paper SNA without antibiotics may reduce antibiotic consumption compared to paper SNA and delayed antibiotics (OR=0.27 (95%CI: 0.15-0.51, some RoB; 1 study, 206 participants). Video SNA, oral SNA, read-only websites, and web-based modules may increase parental knowledge (ORs 2.23-4.52). Video SNA and web-based modules may improve parental satisfaction (ORs 1.64-4.08). CONCLUSION: Paper SNA (with oral SNA) may reduce antibiotic use and return visits. Video, oral, and online SNA, may improve parental knowledge while video SNA and web-based modules may increase parental satisfaction.

Enhancing chemotherapeutic efficacy: Niosome-encapsulated Dox-Cis with MUC-1 aptamer.

BACKGROUND: Cancer remains a formidable global health challenge, currently affecting nearly 20 million individuals worldwide. Due to the absence of universally effective treatments, ongoing research explores diverse strategies to combat this disease. Recent efforts have concentrated on developing combined drug regimens and targeted therapeutic approaches. OBJECTIVE: This study aimed to investigate the anticancer efficacy of a conjugated drug system, consisting of doxorubicin and cisplatin (Dox-Cis), encapsulated within niosomes and modified with MUC-1 aptamers to enhance biocompatibility and target specific cancer cells. METHODS: The chemical structure of the Dox-Cis conjugate was characterized using Fourier Transform Infrared Spectroscopy (FTIR) and Liquid Chromatography Quadrupole Time-of-Flight Mass Spectrometry (LC-Q-TOF/MS). The zeta potential and morphological parameters of the niosomal vesicles were determined through Dynamic Light Scattering (DLS) and Transmission Electron Microscopy (TEM). In vitro assessments of cell viability and apoptosis were conducted on MUC-1 positive HeLa cells and MUC-1 negative U87 cells. RESULTS: The findings confirmed the successful conjugation of Dox and Cis within the niosomes. The Nio/Dox-Cis/MUC-1 formulation demonstrated enhanced efficacy compared to the individual drugs and their unencapsulated combination in both cell lines. Notably, the Nio/Dox-Cis/MUC-1 formulation exhibited greater effectiveness on HeLa cells (38.503 ± 1.407) than on U87 cells (46.653 ± 1.297). CONCLUSION: The study underscores the potential of the Dox-Cis conjugate as a promising strategy for cancer treatment, particularly through platforms that facilitate targeted drug delivery to cancer cells. This targeted approach could lead to more effective and personalized cancer therapies.

Factors associated with non-response and nutrional status of non-responders at 6-month post-discharge: a cohort study nested in a MUAC-based nutrition programme for acutely malnourished children in Mirriah, Niger.

Background: In the treatment of acute malnutrition (AM), non-response is considered a treatment failure for not meeting recovery criteria within a therapeutic window of 12-16 weeks, but this category of children is misunderstood. As current research emphasizes ways to simplify and optimize treatment protocols, non-response emerges as a new issue to enhance program efficiency. Methods: A prospective cohort study was conducted from 2019 to 2020 at two health centres in Mirriah, Niger among children aged 6-59 months with uncomplicated AM treated under the Optimising treatment for Acute MAlnutrition (OptiMA) protocol. Children who did not meet recovery criteria by 12 weeks (mid-upper arm circumference (MUAC) ≥125 mm without oedema for two consecutive weeks) were classified as non-responders. Non-responders received a home visit six-months post-discharge. Logistic regression was used to analyze factors associated with non-responders compared with children who recovered. Results: Of the 1,112 children enrolled, 909 recovered and 139 were non-responders, of which 127 (80.6%) had significant MUAC gain (mean: +9.6 mm, sd = 5.1) at discharge. Girls (adjusted hazard ratio (aHR) = 2.07, 95% CI 1.33-3.25), children <12 months of age (aHr = 4.23, 95% CI 2.02-9.67), those with a MUAC <115 mm (aHR = 11.1, 95% CI 7.23-17.4) or severe stunting (aHR = 2.5, 1.38-4.83) at admission and a negative or flat MUAC trajectory between admission and week 4 (aHR = 4.66, 95% CI 2.54-9.13) were more likely to be non-responders. The nutritional status of non-responders had generally improved 6 months after discharge, but only 40% had achieved MUAC ≥125 mm. Conclusion: Non-responders are not a homogeneous group; while most children ultimately show significant nutritional improvement, rapid hospital referral is crucial for those not gaining MUAC early in treatment. As efforts to expand MUAC-based programming progress, adapting exit criterion and/or providing additional food supplementation with smaller daily ration for children with risk factors discussed here may help improve programme efficiency without adding to the cost of treatment.

Observed-to-expected lung-area-to-head-circumference ratio on ultrasound examination vs total fetal lung volume on magnetic resonance imaging in prediction of survival in fetuses with left-sided diaphragmatic hernia.

OBJECTIVE: To assess and compare the value of antenatally determined observed-to-expected (O/E) lung-area-to-head-circumference ratio (LHR) on ultrasound examination vs O/E total fetal lung volume (TFLV) on magnetic resonance imaging (MRI) examination to predict postnatal survival of fetuses with isolated, expectantly managed left-sided congenital diaphragmatic hernia (CDH). METHODS: This was a multicenter retrospective study including all consecutive fetuses with isolated CDH that were managed expectantly in Mannheim, Germany, and in five other European centers, that underwent at least one ultrasound examination for measurement of O/E-LHR and one MRI scan for measurement of O/E-TFLV during pregnancy. All MRI data were centralized, and lung volumes were measured by two experienced operators blinded to the pre- and postnatal data. Multiple logistic regression analyses were performed to examine the effect on survival at hospital discharge of various perinatal variables, including the center of management. In left-sided CDH with intrathoracic herniation of the liver, receiver-operating-characteristics (ROC) curves were constructed separately for cases from Mannheim and the other five European centers and were used to compare O/E-TFLV and O/E-LHR in the prediction of postnatal survival. RESULTS: From Mannheim, 309 patients were included with a median gestational age (GA) at ultrasound examination of 29.6 (range, 19.7-39.1) weeks and median GA at MRI examination of 31.1 (range, 18.0-39.9) weeks. From the other five European centers, 116 patients were included with a median GA at ultrasound examination of 26.7 (range, 20.6-37.6) weeks and median GA at MRI examination of 27.7 (range, 21.3-37.9) weeks. Regression analysis demonstrated that the survival rates at discharge were lower in left-sided CDH (odds ratio (OR), 0.349 (95% CI, 0.133-0.918), P = 0.033) and those with intrathoracic liver (OR, 0.297 (95% CI, 0.141-0.628), P = 0.001), and higher with increasing O/E-TFLV (OR, 1.123 (95% CI, 1.079-1.170), P < 0.001), advanced GA at birth (OR, 1.294 (95% CI, 1.055-1.588), P = 0.013) and when birth occurred in Mannheim (OR, 7.560 (95% CI, 3.368-16.967), P < 0.001). Given the difference in survival rate between Mannheim and the five other European centers, ROC curve comparisons between the two imaging modalities were presented separately. For cases of left-sided CDH with intrathoracic herniation of the liver, pairwise comparison showed no significant difference between the area under the ROC curves for the prediction of postnatal survival between O/E-TFLV and O/E-LHR in Mannheim (mean difference = 0.025, P = 0.610, standard error = 0.050), whereas there was a significant difference in the other European centers studied (mean difference = 0.056, P = 0.033, standard error = 0.056). CONCLUSIONS: In fetuses with left-sided CDH and intrathoracic herniation of the liver, the predictive value for postnatal survival of O/E-TFLV on MRI examination and O/E-LHR on ultrasound examination was similar in one center (Mannheim), but O/E-TFLV had better predictive value compared to O/E-LHR in the five other European centers. Hence, in these five European centers, MRI should be included in the diagnostic process for left-sided CDH. © 2024 International Society of Ultrasound in Obstetrics and Gynecology.

Accuracy of routine laboratory tests to predict mortality and deterioration to severe or critical COVID-19 in people with SARS-CoV-2.

BACKGROUND: Identifying patients with COVID-19 disease who will deteriorate can be useful to assess whether they should receive intensive care, or whether they can be treated in a less intensive way or through outpatient care. In clinical care, routine laboratory markers, such as C-reactive protein, are used to assess a person's health status. OBJECTIVES: To assess the accuracy of routine blood-based laboratory tests to predict mortality and deterioration to severe or critical (from mild or moderate) COVID-19 in people with SARS-CoV-2. SEARCH METHODS: On 25 August 2022, we searched the Cochrane COVID-19 Study Register, encompassing searches of various databases such as MEDLINE via PubMed, CENTRAL, Embase, medRxiv, and ClinicalTrials.gov. We did not apply any language restrictions. SELECTION CRITERIA: We included studies of all designs that produced estimates of prognostic accuracy in participants who presented to outpatient services, or were admitted to general hospital wards with confirmed SARS-CoV-2 infection, and studies that were based on serum banks of samples from people. All routine blood-based laboratory tests performed during the first encounter were included. We included any reference standard used to define deterioration to severe or critical disease that was provided by the authors. DATA COLLECTION AND ANALYSIS: Two review authors independently extracted data from each included study, and independently assessed the methodological quality using the Quality Assessment of Prognostic Accuracy Studies tool. As studies reported different thresholds for the same test, we used the Hierarchical Summary Receiver Operator Curve model for meta-analyses to estimate summary curves in SAS 9.4. We estimated the sensitivity at points on the SROC curves that corresponded to the median and interquartile range boundaries of specificities in the included studies. Direct and indirect comparisons were exclusively conducted for biomarkers with an estimated sensitivity and 95% CI of ≥ 50% at a specificity of ≥ 50%. The relative diagnostic odds ratio was calculated as a summary of the relative accuracy of these biomarkers. MAIN RESULTS: We identified a total of 64 studies, including 71,170 participants, of which 8169 participants died, and 4031 participants deteriorated to severe/critical condition. The studies assessed 53 different laboratory tests. For some tests, both increases and decreases relative to the normal range were included. There was important heterogeneity between tests and their cut-off values. None of the included studies had a low risk of bias or low concern for applicability for all domains. None of the tests included in this review demonstrated high sensitivity or specificity, or both. The five tests with summary sensitivity and specificity above 50% were: C-reactive protein increase, neutrophil-to-lymphocyte ratio increase, lymphocyte count decrease, d-dimer increase, and lactate dehydrogenase increase. Inflammation For mortality, summary sensitivity of a C-reactive protein increase was 76% (95% CI 73% to 79%) at median specificity, 59% (low-certainty evidence). For deterioration, summary sensitivity was 78% (95% CI 67% to 86%) at median specificity, 72% (very low-certainty evidence). For the combined outcome of mortality or deterioration, or both, summary sensitivity was 70% (95% CI 49% to 85%) at median specificity, 60% (very low-certainty evidence). For mortality, summary sensitivity of an increase in neutrophil-to-lymphocyte ratio was 69% (95% CI 66% to 72%) at median specificity, 63% (very low-certainty evidence). For deterioration, summary sensitivity was 75% (95% CI 59% to 87%) at median specificity, 71% (very low-certainty evidence). For mortality, summary sensitivity of a decrease in lymphocyte count was 67% (95% CI 56% to 77%) at median specificity, 61% (very low-certainty evidence). For deterioration, summary sensitivity of a decrease in lymphocyte count was 69% (95% CI 60% to 76%) at median specificity, 67% (very low-certainty evidence). For the combined outcome, summary sensitivity was 83% (95% CI 67% to 92%) at median specificity, 29% (very low-certainty evidence). For mortality, summary sensitivity of a lactate dehydrogenase increase was 82% (95% CI 66% to 91%) at median specificity, 60% (very low-certainty evidence). For deterioration, summary sensitivity of a lactate dehydrogenase increase was 79% (95% CI 76% to 82%) at median specificity, 66% (low-certainty evidence). For the combined outcome, summary sensitivity was 69% (95% CI 51% to 82%) at median specificity, 62% (very low-certainty evidence). Hypercoagulability For mortality, summary sensitivity of a d-dimer increase was 70% (95% CI 64% to 76%) at median specificity of 56% (very low-certainty evidence). For deterioration, summary sensitivity was 65% (95% CI 56% to 74%) at median specificity of 63% (very low-certainty evidence). For the combined outcome, summary sensitivity was 65% (95% CI 52% to 76%) at median specificity of 54% (very low-certainty evidence). To predict mortality, neutrophil-to-lymphocyte ratio increase had higher accuracy compared to d-dimer increase (RDOR (diagnostic Odds Ratio) 2.05, 95% CI 1.30 to 3.24), C-reactive protein increase (RDOR 2.64, 95% CI 2.09 to 3.33), and lymphocyte count decrease (RDOR 2.63, 95% CI 1.55 to 4.46). D-dimer increase had higher accuracy compared to lymphocyte count decrease (RDOR 1.49, 95% CI 1.23 to 1.80), C-reactive protein increase (RDOR 1.31, 95% CI 1.03 to 1.65), and lactate dehydrogenase increase (RDOR 1.42, 95% CI 1.05 to 1.90). Additionally, lactate dehydrogenase increase had higher accuracy compared to lymphocyte count decrease (RDOR 1.30, 95% CI 1.13 to 1.49). To predict deterioration to severe disease, C-reactive protein increase had higher accuracy compared to d-dimer increase (RDOR 1.76, 95% CI 1.25 to 2.50). The neutrophil-to-lymphocyte ratio increase had higher accuracy compared to d-dimer increase (RDOR 2.77, 95% CI 1.58 to 4.84). Lastly, lymphocyte count decrease had higher accuracy compared to d-dimer increase (RDOR 2.10, 95% CI 1.44 to 3.07) and lactate dehydrogenase increase (RDOR 2.22, 95% CI 1.52 to 3.26). AUTHORS' CONCLUSIONS: Laboratory tests, associated with hypercoagulability and hyperinflammatory response, were better at predicting severe disease and mortality in patients with SARS-CoV-2 compared to other laboratory tests. However, to safely rule out severe disease, tests should have high sensitivity (> 90%), and none of the identified laboratory tests met this criterion. In clinical practice, a more comprehensive assessment of a patient's health status is usually required by, for example, incorporating these laboratory tests into clinical prediction rules together with clinical symptoms, radiological findings, and patient's characteristics.

Biomechanical analysis of stabilization for thoracolumbar anterior spinal failure caused by osteolytic lesions, a finite element comparison of direct lateral corpectomy and posterior long segment instrumentation.

BACKGROUND CONTEXT: Osteolytic lesions caused by infection or metastatic disease of the spine can induce instability. Different surgical strategies are available to restore stability in this scenario, however little is known how various reconstruction techniques affect spinal biomechanics. PURPOSE: To analyze and quantify the biomechanical effects of three different surgical reconstruction techniques in the treatment of a T12 osteolytic model. STUDY DESIGN/SETTING: Finite element analysis of the thoracic spine with a T12 osteolytic lesion. METHODS: Using CT scans from a 20-year-old man without structural deformity, simulation of an osteolytic lesion with a 50% defect at the posterior aspect of T12 vertebral body was created by a 490 N vertical force to T9. Next, three common instrumentation techniques treating the osteolytic lesion were modeled and biomechanically tested. These included: Model A, corpectomy with short segment fixation (T11-L1) and two long-segment instrumentations; Model B long segment fixation with triple rod construct; Model C long segment fixation with dual rod construct. A load of 480N was then applied on the spine models in vertically downward direction on T9. Von Mises stresses were measured (MPa) in the discs, vertebrae, and implants. RESULTS: Model A demonstrated the lowest stress on construct material, adjacent vertebral bodies, and discs but increased stress on the instrumented vertebrae. Model B was more rigid and demonstrated lower construct stress compared to Model C. However, Model C had the lowest vertebral body stress in flexion, extension, and lateral bending in the most upper instrumented vertebral body, but the highest screw pull-out stress when compared to Model A and Model B. CONCLUSIONS: This osteolytic T12 model provides unique biomechanical data that can help to tailor surgical strategies in select scenarios. While optimal outcomes are best achieved with a construct tailored to a specific patient's need for stabilization, our findings can be generalized for instances of cancerous lesions, low bone density, and infectious causes. CLINICAL RELEVANCE: The results of this study can help with the choice of appropriate surgical reconstruction technique based on patient-specific characteristics.

Contrast Sensitivity and Low Contrast Visual Acuity in Children With Normal Visual Acuity.

PURPOSE: To measure and report the distribution of distance and near contrast sensitivity (CS) and low contrast visual acuity (LCVA) at 5% and 2.5% contrast in children aged 5-15 years with normal visual acuity (VA). DESIGN: Prospective, cross-sectional study. SETTING: Schools in Southern India. STUDY POPULATION: One thousand fifty-two children aged 5 to 15 years (mean age 10.61 ± 2.85 years) with a presenting visual acuity of 0.00 logMAR or better in both eyes and a stereo acuity of 40 seconds of arc or better were recruited from nine schools. Repeatability of contrast sensitivity and low contrast visual acuities were tested in 246 children. Pelli-Robson charts were used to measure the distance and near contrast sensitivity at 1 m and 40 cm, respectively. The low contrast visual acuity was recorded at 5% and 2.5% contrast using LEA Symbols at 3 m. RESULTS: Overall, the mean ± SD, (95% CI) monocular distance and near CS were 1.75 ± 0.11 (1.76-1.75) logCS and 1.72 ± 0.10 (1.73-1.71) logCS, respectively. The mean LCVA at 5% and 2.5% contrasts were 0.20 ± 0.10 (0.21-0.20) logMAR and 0.39 ± 0.11 (0.40-0.39) logMAR, respectively. Distance and near CS gradually improved till the ages of 11 and 13, respectively, and then plateaued. Similarly, LCVA at 5% and 2.5% contrasts gradually improved till age ten before plateauing. The Coefficient of Repeatability (CoR) for CS was ±0.02 logCS for distance, ±0.05 logCS for near, and ±0.01 logMAR for both LCVA contrasts. CONCLUSIONS: The study provides age-specific normative values for distance and near CS, and LCVA in a cohort of children aged 5-15 years. These results are important to understand the impact of ocular conditions on CS in children and have utility in clinical evaluations.

Normothermic and hypothermic machine perfusion preservation versus static cold storage for deceased donor kidney transplantation.

BACKGROUND: Kidney transplantation is the optimal treatment for kidney failure. Donation, transport and transplant of kidney grafts leads to significant ischaemia reperfusion injury. Static cold storage (SCS), whereby the kidney is stored on ice after removal from the donor until the time of implantation, represents the simplest preservation method. However, technology is now available to perfuse or "pump" the kidney during the transport phase ("continuous") or at the recipient centre ("end-ischaemic"). This can be done at a variety of temperatures and using different perfusates. The effectiveness of these treatments manifests as improved kidney function post-transplant. OBJECTIVES: To compare machine perfusion (MP) technologies (hypothermic machine perfusion (HMP) and (sub) normothermic machine perfusion (NMP)) with each other and with standard SCS. SEARCH METHODS: We contacted the information specialist and searched the Cochrane Kidney and Transplant Register of Studies until 15 June 2024 using search terms relevant to this review. Studies in the Register are identified through searches of CENTRAL, MEDLINE, and EMBASE, conference proceedings, the International Clinical Trials Registry Platform (ICTRP) Search Portal, and ClinicalTrials.gov. SELECTION CRITERIA: All randomised controlled trials (RCTs) and quasi-RCTs comparing machine perfusion techniques with each other or versus SCS for deceased donor kidney transplantation were eligible for inclusion. All donor types were included (donor after circulatory death (DCD) and brainstem death (DBD), standard and extended/expanded criteria donors). Both paired and unpaired studies were eligible for inclusion. DATA COLLECTION AND ANALYSIS: The results of the literature search were screened, and a standard data extraction form was used to collect data. Both of these steps were performed by two independent authors. Dichotomous outcome results were expressed as risk ratios (RR) with 95% confidence intervals (CI). Survival analyses (time-to-event) were performed with the generic inverse variance meta-analysis of hazard ratios (HR). Continuous scales of measurement were expressed as a mean difference (MD). Random effects models were used for data analysis. The primary outcome was the incidence of delayed graft function (DGF). Secondary outcomes included graft survival, incidence of primary non-function (PNF), DGF duration, economic implications, graft function, patient survival and incidence of acute rejection. Confidence in the evidence was assessed using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach. MAIN RESULTS: Twenty-two studies (4007 participants) were included. The risk of bias was generally low across all studies and bias domains. The majority of the evidence compared non-oxygenated HMP with standard SCS (19 studies). The use of non-oxygenated HMP reduces the rate of DGF compared to SCS (16 studies, 3078 participants: RR 0.78, 95% CI 0.69 to 0.88; P < 0.0001; I2 = 31%; high certainty evidence). Subgroup analysis revealed that continuous (from donor hospital to implanting centre) HMP reduces DGF (high certainty evidence). In contrast, this benefit over SCS was not seen when non-oxygenated HMP was not performed continuously (low certainty evidence). Non-oxygenated HMP reduces DGF in both DCD and DBD settings in studies performed in the 'modern era' and when cold ischaemia times (CIT) were short. The number of perfusions required to prevent one episode of DGF was 7.69 and 12.5 in DCD and DBD grafts, respectively. Continuous non-oxygenated HMP versus SCS also improves one-year graft survival (3 studies, 1056 participants: HR 0.46, 0.29 to 0.75; P = 0.002; I2 = 0%; high certainty evidence). Assessing graft survival at maximal follow-up confirmed a benefit of continuous non-oxygenated HMP over SCS (4 studies, 1124 participants (follow-up 1 to 10 years): HR 0.55, 95% CI 0.40 to 0.77; P = 0.0005; I2 = 0%; high certainty evidence). This effect was not seen in studies where HMP was not continuous. The effect of non-oxygenated HMP on our other outcomes (PNF, incidence of acute rejection, patient survival, hospital stay, long-term graft function, duration of DGF) remains uncertain. Studies performing economic analyses suggest that HMP is either cost-saving (USA and European settings) or cost-effective (Brazil). One study investigated continuous oxygenated HMP versus non-oxygenated HMP (low risk of bias in all domains); the simple addition of oxygen during continuous HMP leads to additional benefits over non-oxygenated HMP in DCD donors (> 50 years), including further improvements in graft survival, improved one-year kidney function, and reduced acute rejection. One large, high-quality study investigated end-ischaemic oxygenated HMP versus SCS and found end-ischaemic oxygenated HMP (median machine perfusion time 4.6 hours) demonstrated no benefit compared to SCS. The impact of longer periods of end-ischaemic HMP is unknown. One study investigated NMP versus SCS (low risk of bias in all domains). One hour of end ischaemic NMP did not improve DGF compared with SCS alone. An indirect comparison revealed that continuous non-oxygenated HMP (the most studied intervention) was associated with improved graft survival compared with end-ischaemic NMP (indirect HR 0.31, 95% CI 0.11 to 0.92; P = 0.03). No studies investigated normothermic regional perfusion (NRP) or included any donors undergoing NRP. AUTHORS' CONCLUSIONS: Continuous non-oxygenated HMP is superior to SCS in deceased donor kidney transplantation, reducing DGF, improving graft survival and proving cost-effective. This is true for both DBD and DCD kidneys, both short and long CITs, and remains true in the modern era (studies performed after 2008). In DCD donors (> 50 years), the simple addition of oxygen to continuous HMP further improves graft survival, kidney function and acute rejection rate compared to non-oxygenated HMP. Timing of HMP is important, and benefits have not been demonstrated with short periods (median 4.6 hours) of end-ischaemic HMP. End-ischaemic NMP (one hour) does not confer meaningful benefits over SCS alone and is inferior to continuous HMP in an indirect comparison of graft survival. Further studies assessing NMP for viability assessment and therapeutic delivery are warranted and in progress.

White matter organisation of sensorimotor tracts is associated with motor imagery in childhood.

Despite the important role of motor imagery (MI) in motor development, our understanding of the contribution of white matter fibre properties to MI performance in childhood remains limited. To provide novel insight into the white matter correlates of MI performance, this study examined the association between white matter fibre properties and motor imagery performance in a sample of typically developing children. High angular diffusion weighted imaging data were collected from 22 typically developing children aged 6-14 years (12 female, MAge= 10.56). Implicit motor imagery performance was assessed using a mental hand rotation paradigm. The cerebellar peduncles and the superior longitudinal fasciculus were reconstructed using TractSeg, a semi-automated method. For each tract, white matter microstructure (fibre density, FD) and morphology (fibre bundle cross-section, FC) were estimated using Fixel-Based Analysis. Permutation-based inference testing and partial correlation analyses demonstrated that higher FC in the middle cerebellar peduncles was associated with better MI performance. Tract-based region of interest analyses showed that higher FC in the middle and superior cerebellar peduncles were associated with better MI performance. Results suggest that white matter connectivity along the cerebellar peduncles may facilitate MI performance in childhood. These findings advance our understanding of the neurobiological systems that underlie MI performance in childhood and provide early evidence for the relevance of white matter sensorimotor pathways to internal action representations.

Cost and cost-effectiveness of treatments for rheumatic heart disease in low- and middle-income countries: a systematic review protocol.

OBJECTIVE: This review will synthesize studies on costs, the impact of these costs, and the cost-effectiveness of treatments for rheumatic heart disease (RHD) in low- and middle-income countries. INTRODUCTION: RHD incurs high costs owing to its clinical complexity, surgical treatments, and prolonged hospital stays. Thus, the disease has a substantial economic impact on the health system, patients, and their families. No systematic review on economic evidence of treatments for RHD has been published to date. INCLUSION CRITERIA: This review will consider all cost and cost-effectiveness studies on RHD treatments for children and young adults (5─30 years) residing in low- and middle-income countries. METHODS: The review will follow the JBI methodology for systematic reviews of economic evaluation evidence. The search strategy will locate published and unpublished studies in English. Systematic searches will be conducted in MEDLINE (PubMed), MEDLINE (Ovid), Embase (Ovid), Scopus, CINAHL (EBSCOhost), National Health Service Economic Evaluation Databases, Pediatric Economic Database Evaluation, and Cost-Effectiveness Analysis Registry. Two independent reviewers will screen titles and abstracts, followed by a full-text review based on the inclusion criteria. Data will be extracted using a modified JBI data extraction form for economic evaluations. JBI's Dominance Ranking Matrix for economic evaluations will be used to summarize and compare the results of cost and cost-effectiveness studies. The Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) approach will be used to assess the certainty of economic evidence for outcomes related to resource use. REVIEW REGISTRATION: PROSPERO CRD42023425850.

A review of the fungal polysaccharides as natural biopolymers: Current applications and future perspective.

As a unique natural resource, fungi are a sustainable source of lipids, polysaccharides, vitamins, proteins, and other nutrients. As a result, they have beneficial medicinal and nutritional properties. Polysaccharides are among the most significant bioactive components found in fungi. Increasing research has revealed that fungal polysaccharides (FPS) contain a variety of bioactivities, including antitumor, antioxidant, immunomodulatory, anti-inflammatory, hepatoprotective, cardioprotective, and anti-aging properties. However, the exact knowledge about FPS and their applications related to their future possibilities must be thoroughly examined to enhance a better understanding of this sustainable biopolymer source. Therefore, FPS' biological applications and their role in the food and feed industry, agriculture, and cosmetics applications were all discussed in this work. In addition, this review highlighted the mode of action of FPS on human diseases by regulating gut microbiota and discussed the mechanism of FPS as antioxidants in the living cell. The structure-activity connections of FPS were also highlighted and explored. Moreover, future perspectives were listed to pave the way for future studies of FPS applications. Hence, this study can be a scientific foundation for future FPS research and industrial applications.

Predictors of musculoskeletal disorders among special education teachers in Sabah, Malaysia.

Special education teachers encounter considerable occupational challenges, yet there is limited information concerning musculoskeletal disorders (MSD) within this group. Therefore, this study aimed to address this gap by determining the prevalence of MSD, investigating associated factors of MSD, and identifying predictors of MSD among special education teachers. A cross-sectional study was conducted among special education teachers in Kota Kinabalu and Penampang, Sabah. Data were collected through self-administered questionnaires and musculoskeletal fitness assessments. Chi-square tests and independent t-tests were utilized to determine factors associated with MSD, while multiple logistic regression was performed to develop a comprehensive predictive model for MSD, which was then validated and tested for model fitness. A total of 122 individuals participated in the study, yielding a response rate of 95 %. The findings revealed a high prevalence of MSD (77.9 %) among special education teachers, with the lower back, shoulder, neck, knee, upper back, and foot being the most affected regions. The multivariable regression model identified several predictors of MSD, including marital status (adjusted odds ratio [aOR] = 4.78, 95 % confidence interval [CI] = 1.49-15.40), body fat percentage (aOR = 1.06, 95 % CI = 1.00-1.12), teaching in prolonged standing for few days a week (aOR = 3.20, 95 % CI = 0.99-10.29) or every day (aOR = 6.20, 95 % CI = 1.44-26.70), mindfulness (aOR = 0.47, 95 % CI = 0.22-0.98), and back extensor strength (aOR = 5.86, 95 % CI = 1.92-17.92). This study highlights the necessity of implementing interventions focusing on the ergonomic, psychological, and musculoskeletal fitness components to mitigate the prevalence of MSD and improve the overall well-being of special education teachers.

A Comprehensive Study on the Hematological Progression of Sickle Cell Disease Patients with COVID-19 at the Center for Research and Control of Sickle Cell Disease, Bamako.

The Coronavirus disease 2019 pandemic is a real crisis that has exposed the unpreparedness of many healthcare systems worldwide. Several underlying health conditions have been identified as risk factors, including sickle cell disease, a chronic illness with various complications that can increase the risk of severe COVID-19 infection. Our study aimed to investigate the profile of sickle cell patients diagnosed with COVID-19 and explore any potential relationship between these two conditions. We analyzed data from 11 sickle cell patients who contracted COVID-19 between June and December 2020 and were treated at the CRLD (Center for Sickle Cell Disease and Research). The patients' COVID-19 diagnosis was confirmed using the (Real-Time Reverse Transcriptase-Polymerase Chain Reaction) RT-PCR technique on nasopharyngeal swab samples and/or based on clinical and radiological findings, including CT scans. The patients consisted of 7 males and 4 females, with a mean age of 40 ± 12 years. The sickle cell phenotypes observed were SC (45.4%), SS (36.37%), and Sß± thalassemia (18.2%). During the COVID-19 infection, we observed a slight increase in white blood cell and platelet counts, but a decrease in mean hemoglobin levels and red blood cells. Only 3 out of 11 patients (28%) had a fever at the time of diagnosis. Three patients required red blood cell transfusions due to severe anemia, and 7 out of 11 patients (63.6%) were hospitalized, with one patient admitted to the intensive care unit due to pulmonary embolism. All patients recovered from COVID-19.

Cemiplimab plus chemotherapy versus chemotherapy alone in non-small cell lung cancer with PD-L1 ≥ 1 %: A subgroup analysis from the EMPOWER-Lung 3 part 2 trial.

OBJECTIVES: EMPOWER-Lung 3 part 2 (NCT03409614), a double-blind, placebo-controlled phase 3 study, assessed cemiplimab (anti-programmed cell death protein 1) plus chemotherapy versus chemotherapy alone in patients with advanced non-small cell lung cancer (NSCLC) without EGFR, ALK, or ROS1 aberrations, regardless of histology or PD-L1 expression levels. We report results from subgroup analysis of patients with PD-L1 expression ≥ 1 %. MATERIALS AND METHODS: Patients were randomized to receive cemiplimab 350 mg or placebo with chemotherapy every 3 weeks for up to 108 weeks. Overall survival (OS), progression-free survival (PFS), overall response rates (ORRs), patient-reported outcomes (PROs), and safety were assessed. RESULTS: Of the 327 patients with PD-L1 ≥ 1 % (466 in the overall study), 217 received cemiplimab plus chemotherapy and 110 received chemotherapy alone. After median follow-up of 28.0 months, median OS for cemiplimab plus chemotherapy was 23.5 months (95 % confidence interval [CI]: 20.9-27.2) vs. 12.1 months (95 % CI: 10.1-15.7) for chemotherapy alone (hazard ratio [HR] = 0.51, 95 % CI: 0.38-0.69, P < 0.0001); median PFS was 8.3 months (95 % CI: 6.7-10.8) versus 5.5 months (95 % CI: 4.3-6.2; HR = 0.48; 95 % CI: 0.37-0.62, P < 0.0001), and ORR was 47.9 % versus 22.7 %, respectively. PRO results favored cemiplimab plus chemotherapy over chemotherapy alone. Improved efficacy over chemotherapy alone was observed in both squamous and non-squamous histology. Safety was consistent with previous reports. CONCLUSION: In this subgroup analysis from EMPOWER-Lung 3 part 2, cemiplimab plus chemotherapy demonstrated clinical benefit over chemotherapy alone in patients with advanced squamous or non-squamous NSCLC with PD-L1 ≥ 1 %.

Building and analyzing metacells in single-cell genomics data.

The advent of high-throughput single-cell genomics technologies has fundamentally transformed biological sciences. Currently, millions of cells from complex biological tissues can be phenotypically profiled across multiple modalities. The scaling of computational methods to analyze and visualize such data is a constant challenge, and tools need to be regularly updated, if not redesigned, to cope with ever-growing numbers of cells. Over the last few years, metacells have been introduced to reduce the size and complexity of single-cell genomics data while preserving biologically relevant information and improving interpretability. Here, we review recent studies that capitalize on the concept of metacells-and the many variants in nomenclature that have been used. We further outline how and when metacells should (or should not) be used to analyze single-cell genomics data and what should be considered when analyzing such data at the metacell level. To facilitate the exploration of metacells, we provide a comprehensive tutorial on the construction and analysis of metacells from single-cell RNA-seq data ( https://github.com/GfellerLab/MetacellAnalysisTutorial ) as well as a fully integrated pipeline to rapidly build, visualize and evaluate metacells with different methods ( https://github.com/GfellerLab/MetacellAnalysisToolkit ).

Is ChatGPT reliable and accurate in answering pharmacotherapy-related inquiries in both Turkish and English?

INTRODUCTION: Artificial intelligence (AI), particularly ChatGPT, is becoming more and more prevalent in the healthcare field for tasks such as disease diagnosis and medical record analysis. The objective of this study is to evaluate the proficiency and accuracy of ChatGPT in different domains of clinical pharmacy cases and queries. METHODS: The study NAPLEX® Review Questions, 4th edition, pertaining to 10 different chronic conditions compared ChatGPT's responses to pharmacotherapy cases and questions obtained from McGraw Hill's, alongside the answers provided by the book's authors. The proportion of correct responses was collected and analyzed using the Statistical Package for the Social Sciences (SPSS) version 29. RESULTS: When tested in English, ChatGPT had substantially higher mean scores than when tested in Turkish. The average accurate score for English and Turkish was 0.41 ± 0.49 and 0.32 ± 0.46, respectively, p = 0.18. Responses to queries beginning with "Which of the following is correct?" are considerably more precise than those beginning with "Mark all the incorrect answers?" 0.66 ± 0.47 as opposed to 0.16 ± 0.36; p = 0.01 in English language and 0.50 ± 0.50 as opposed to 0.14 ± 0.34; p < 0.05in Turkish language. CONCLUSION: ChatGPT displayed a moderate level of accuracy while responding to English inquiries, but it displayed a slight level of accuracy when responding to Turkish inquiries, contingent upon the question format. Improving the accuracy of ChatGPT in languages other than English requires the incorporation of several components. The integration of the English version of ChatGPT into clinical practice has the potential to improve the effectiveness, precision, and standard of patient care provision by supplementing personal expertise and professional judgment. However, it is crucial to utilize technology as an adjunct and not a replacement for human decision-making and critical thinking.