Pro-thrombotic autoantibodies targeting Platelet Factor 4/polyanion are associated with pediatric cerebral malaria.

BACKGROUND: Features of consumptive coagulopathy and thromboinflammation are prominent in cerebral malaria (CM). We hypothesized that thrombogenic autoantibodies contribute to a procoagulant state in CM. METHODS: Plasma from children with uncomplicated malaria (UM, n = 124) and CM (n = 136) was analyzed by ELISA for a panel of 8 autoantibodies including anti-Platelet Factor 4/polyanion (anti-PF4/P), anti-Phospholipid, anti-Phosphatidylserine, anti-Myeloperoxidase, anti-Proteinase 3, anti-dsDNA, anti-Beta-2-Glycoprotein I (ß2GPI), and anti-Cardiolipin. Non-malaria coma (NMC, n = 49) and healthy controls (HC, n = 56) were assayed for comparison. Associations with clinical and immune biomarkers were determined using univariate and logistic regression analyses. RESULTS: Median anti-PF4/P and anti-PS IgG levels were elevated with malaria infection relative to HC (P < 0.001) and NMC (PF4/P: P < 0.001). Anti-PF4/P IgG levels were elevated in CM (median = 0.27, IQR: 0.19-0.41) compared to UM (median = 0.19, IQR: 0.14-0.22, P ≤ 0.0001). Anti-PS IgG levels did not differ between UM and CM (P = 0.39). When CM cases were stratified by malaria retinopathy (Ret) status, levels of anti-PF4/P IgG correlated negatively with peripheral platelet count in Ret+ CM cases (Rs = 0.201, P = 0.04) and associated positively with mortality (OR = 15.2, 95% CI: 1.02-275, P = 0.048). Plasma from CM patients induced a greater platelet activation capacity in an ex-vivo assay relative to plasma from UM patients (P = 0.02). Platelet activation was associated with anti-PF4/P IgG levels (Rs = 0.293, P = 0.035). CONCLUSIONS: Thrombosis mediated by elevated anti-PF4/P autoantibodies may be one mechanism contributing to the clinical complications of CM.

Assessing the use of anti-PD1 monotherapy as adjuvant therapy and determinants of treatment choice in stage III cutaneous melanoma in the US.

BACKGROUND: The objective of this study was to describe real-world adjuvant therapy (AT) use by disease substage and assess determinants of treatment choice among patients with stage III melanoma. METHODS: This non-interventional retrospective study included survey responses and data from patient records provided by US medical oncologists. Survey responses, patient demographic/clinical characteristics, treatment utilization, and reasons for treatment were reported descriptively. The association between patient and disease characteristics and AT selection was assessed using logistic and multinomial regression models, overall and stratified by AJCC8 substage (IIIA vs. IIIB/C/D) and type of AT received (anti-PD1 monotherapy, BRAF/MEK, no AT), respectively. RESULTS: In total 152 medical oncologists completed the survey and reviewed the charts of 507 patients (168 stage IIIA; 339 stages IIIB/IIIC/IIID); 405 (79.9%) patients received AT (360/405 (88.9%) received anti-PD1 therapy; 45/405 (11.1%) received BRAF/MEK therapy). Physicians reported clinical guidelines (61.2%), treatment efficacy (37.5%), and ECOG performance status (31.6%) as drivers of AT prescription. Patient-level data confirmed that improving patient outcomes (79%) was the main reason for anti-PD1 prescription; expected limited treatment benefit (37%), patient refusal (36%), and toxicity concerns (30%) were reasons for not prescribing AT. In multivariable analyses stage IIIB/IIIC/IIID disease significantly increased the probability of receiving AT (odds ratio [OR] 1.74) and anti-PD1 therapy (OR 1.82); ECOG 2/3 and Medicaid/no insurance decreased the probability of AT receipt (OR 0.37 and 0.42, respectively) and anti-PD1 therapy (OR 0.41 and 0.42, respectively) among all patients and patients with stage IIIA disease. CONCLUSION: Most patients were given AT with a vast majority treated with an anti-PD1 therapy. Physician- and patient-level evidence confirmed the impact of disease substage on AT use, with stage IIIA patients, patients without adequate insurance coverage, and worse ECOG status having a lower probability of receiving AT.

Frequency, kinetics and determinants of viable SARS-CoV-2 in bioaerosols from ambulatory COVID-19 patients infected with the Beta, Delta or Omicron variants.

Airborne transmission of SARS-CoV-2 aerosol remains contentious. Importantly, whether cough or breath-generated bioaerosols can harbor viable and replicating virus remains largely unclarified. We performed size-fractionated aerosol sampling (Andersen cascade impactor) and evaluated viral culturability in human cell lines (infectiousness), viral genetics, and host immunity in ambulatory participants with COVID-19. Sixty-one percent (27/44) and 50% (22/44) of participants emitted variant-specific culture-positive aerosols <10µm and <5µm, respectively, for up to 9 days after symptom onset. Aerosol culturability is significantly associated with lower neutralizing antibody titers, and suppression of transcriptomic pathways related to innate immunity and the humoral response. A nasopharyngeal Ct <17 rules-in ~40% of aerosol culture-positives and identifies those who are probably highly infectious. A parsimonious three transcript blood-based biosignature is highly predictive of infectious aerosol generation (PPV > 95%). There is considerable heterogeneity in potential infectiousness i.e., only 29% of participants were probably highly infectious (produced culture-positive aerosols <5µm at ~6 days after symptom onset). These data, which comprehensively confirm variant-specific culturable SARS-CoV-2 in aerosol, inform the targeting of transmission-related interventions and public health containment strategies emphasizing improved ventilation.

Sacral fracture stabilisation using dorsal transiliac locking plates: 12 cases (2017-2023).

OBJECTIVES: To describe the clinical presentations, outcomes and complications associated with the use of dorsal transiliac locking plates to stabilise sacral fractures in dogs and cats. MATERIALS AND METHODS: A single-centre retrospective analysis of all patients that presented with sacral fractures between February 2017 and February 2023 that were managed surgically using paired dorsal transiliac locking plates. Twelve animals met the criteria for inclusion in a retrospective clinical case series. An owner questionnaire was employed to assess long-term outcomes. RESULTS: Eleven dogs and one cat with a mean age of 3.1 years (range 0.6 to 8.8) were included. Eleven patients presented following a motor vehicle accident and most were either non-ambulatory (n=8) or displayed severe unilateral hindlimb lameness (n=4). Nine sacral fractures were considered Anderson type II and three Anderson type V. The plate fixation was augmented with additional surgical stabilisation in 11 cases. Eleven patients were ambulatory at discharge and all cases healed uneventfully without major surgical or postoperative complications. Long-term follow-up (>60 days) was available in 10 animals at a mean of 694 days (range 65 to 1805) and owner-assessed outcomes via questionnaire were reported as good to excellent in all cases. CLINICAL SIGNIFICANCE: The application of transiliac locking plates provided sufficient stability to facilitate sacral fracture healing with minimal clinical complications. This method represents a robust and safe option to stabilise sacral fractures in dogs and cats, offering an alternative to iliosacral lag screw fixation.

A modified triple tibial osteotomy for management of canine cranial cruciate ligament disease: retrospective assessment of 309 procedures (2017-2020).

CASE HISTORY: Medical records from a single referral hospital (Animal Referral Hospital, Sinnamon Park, Australia) of dogs treated with modified triple tibial osteotomy (TTO) for management of cranial cruciate ligament (CrCL) disease from June 2017 to June 2020 were reviewed. Modifications to the originally described TTO procedure included a modified wedge angle calculation and performing the tibial osteotomies without the use of pre-drilled guide holes. CLINICAL FINDINGS: A total of 253 dogs met the inclusion criteria. Two dogs were excluded, leaving 251 dogs that had undergone 309 procedures for assessment, and data from these, including complications, were reviewed. Complete, partial competent, and partial incompetent rupture of the cranial cruciate ligament was identified in 202/309 (65.4%), 79/309 (25.6%), and 28/309 (9.1%) stifles, respectively. Medial meniscal injury was identified in 207/309 (67.0%) stifles at the time of initial surgery. TREATMENT AND OUTCOME: Fifty-eight dogs had bilateral procedures, including both single-session and staged surgeries, and 48 of these were available for analyses. The modifications to the TTO procedure described herein resulted in a median wedge angle of 21° and a median post-operative tibial plateau angle of 5.8°. Tibial compression testing following surgery indicated elimination of cranial tibial thrust in all stifles in this series. The most common intra-operative complication was tibial tuberosity fracture (15/309; 4.9%). Minor post-operative complications occurred in 37/309 (12.0%) procedures, with infection being the most common (27/309; 8.7%). Major post-operative complications occurred in 9/309 (2.9%) procedures. The intra- and post-operative complication rates for dogs undergoing bilateral single-session TTO were both 8.3% (2/24). The intra- and post-operative complication rates for dogs undergoing bilateral staged TTO were both 4.2% (1/24). The low number of complications for both the bilateral single-session and bilateral staged TTO groups precluded statistical analysis. All complications resolved uneventfully as determined by the attending surgeon. CLINICAL RELEVANCE: The modified TTO technique described here was safe and effective for the management of canine CrCL disease in the dogs included in the case series. Findings of this study suggest that, with careful case selection, the modified TTO may be performed as a bilateral single-session procedure in dogs with concurrent bilateral cranial cruciate ligament disease. Future studies analysing the effects of these modifications on stifle biomechanics would be beneficial. ABBREVIATIONS: CrCL: Cranial cruciate ligament; SSI: Surgical site infection; TPA: Tibial plateau angle; TPLO: Tibial plateau levelling osteotomy; TTA: Tibial tuberosity advancement; TTO: Triple tibial osteotomy.

MRI prediction of fetal lung volumes and the impact on counselling.

AIM: To assess whether lung volume percentages in congenital diaphragmatic hernia (CDH) differ depending on which formula is used to calculate the expected volume for gestation and any potential impact this may have on perinatal counselling. MATERIALS AND METHODS: Forty-seven patients with left-sided CDH who had undergone fetal magnetic resonance imaging (MRI) at Sheffield Teaching Hospitals were reviewed. The lung volumes were measured on MRI and compared with the volumes that would be expected at the given gestation for each patient. Expected values were calculated using four formulae from the literature and the authors' in-house method. These measurements were used to calculate the percentage total lung volume observed compared with the expected lung volume in a healthy fetus of the same gestation. The differences in percentage lung volumes using these five methods were then compared with how they relate to predicted rates of survival. How predicted survival would change depending on which formula was used to calculate the percentage lung volume was investigated with a view to how this may change the counselling given to a family. RESULTS: In 10/47 (21%) patients, there was no change in the predicted percentage chance of survival depending on which formula was used to calculate the predicted lung volume. In 37/47 (79%), the predicted chance of survival changed depending on which formula was used to calculate the expected lung volume at the given gestation. In 20 (47%) of these cases, the change in predicted survival depending on which formula used was 45% (i.e., from 25% to 70% survival in four and from 50% to 95% survival in 16) and in two cases (4%) this difference was 70% (i.e., from 25% predicted survival to 95% predicted survival). CONCLUSION: There are several different methods for calculating expected lung volumes for any given gestation. When used to estimate the percentage lung volume in patients with CDH, there is a large difference in values depending on which method is used. This in turn leads to a large variation in predicted survival with some patients in this study having either a 25% or 95% chance of survival depending on which method is used. This has a huge impact on perinatal counselling and the difficult decisions made by families.

Statins improve endothelial function via suppression of epigenetic-driven EndMT.

The pleiotropic benefits of statins in cardiovascular diseases that are independent of their lipid-lowering effects have been well documented, but the underlying mechanisms remain elusive. Here we show that simvastatin significantly improves human induced pluripotent stem cell-derived endothelial cell functions in both baseline and diabetic conditions by reducing chromatin accessibility at transcriptional enhanced associate domain elements and ultimately at endothelial-to-mesenchymal transition (EndMT)-regulating genes in a yes-associated protein (YAP)-dependent manner. Inhibition of geranylgeranyltransferase (GGTase) I, a mevalonate pathway intermediate, repressed YAP nuclear translocation and YAP activity via RhoA signaling antagonism. We further identified a previously undescribed SOX9 enhancer downstream of statin-YAP signaling that promotes the EndMT process. Thus, inhibition of any component of the GGTase-RhoA-YAP-SRY box transcription factor 9 (SOX9) signaling axis was shown to rescue EndMT-associated endothelial dysfunction both in vitro and in vivo, especially under diabetic conditions. Overall, our study reveals an epigenetic modulatory role for simvastatin in repressing EndMT to confer protection against endothelial dysfunction.

New Model to Predict Recurrence After Endoscopic Mucosal Resection of Non-pedunculated Colonic Polyps ≥ 20 mm.

BACKGROUND: Polyp recurrence is common after endoscopic mucosal resection (EMR) of non-pedunculated colonic polyps ≥ 20 mm. Two models haven been published for polyp recurrence prediction: Sydney EMR recurrence tool (SERT) and the size, morphology, colonic site, and access to target (SMSA) score. None of these models have been evaluated in a real-world United States (U.S.) cohort. We aimed to evaluate the external validity of these two models and develop a new model. METHODS: Retrospective cohort study of patients with non-pedunculated polyps ≥ 20 mm that underwent EMR between 1/1/2012 and 6/30/2020. Univariate and multivariate analysis were performed to identify predictors of polyp recurrence to build a new model. Receiver Operating Characteristic (ROC) curves for the new model, SERT and a modified version of SMSA were derived and compared. RESULTS: A total of 461 polyps from 461 unique patients were included for analysis. The average polyp size was 29.1 ± 12.4 mm. Recurrence rate at first or second surveillance colonoscopy was 29.0% at a 15.6 months median follow up (IQR 12.3-17.4). A model was created with 4 variables from index colonoscopy: size > 40 mm, tubulovillous adenoma histology, right colon location and piecemeal resection. ROC curves showed that the Area Under the ROC (AUC) for the new model was 0.618, for SERT 0.538 and for mSMSA 0.550. CONCLUSION: SERT score and mSMSA have poor external validity to predict polyp recurrence after EMR of non-pedunculated polyps > 20 mm. Our new model is simpler and performs better in this multiethnic, non-referral cohort from the U.S.

Outcomes of same-day discharge following percutaneous coronary intervention in a rural population.

BACKGROUND: Same-day discharge (SDD) following percutaneous coronary intervention (PCI) is safe, yet the nationwide rate of SDD remains low. The impact that residing in a rural area has on the safety of SDD is unknown. OBJECTIVE: To investigate the safety of SDD compared to next-day discharge (NDD) among PCI patients living in a largely rural area. METHODS: There were 3502 outpatient elective PCIs at a tertiary care center between January 1, 2011 and December 31, 2017. Data from the National Cardiovascular Data Registry CathPCI Registry® and the electronic medical records were obtained for patient demographics, procedural characteristics, and procedural outcomes. Data from the initial PCI in each 365-day period were included in the analysis for each patient. Rural-Urban Commuting Area codes 4-10 were used to define rural status. RESULTS: A total of 2099 (59.9%) PCIs met the inclusion criteria (63% rural). The overall rate of SDD increased over time (4.7% in 2011 to 39.6% in 2017) as radial access increased (14.2% in 2011 to 59.9% in 2017). In this population, a total of 329 PCIs had SDD (15.7%; median (interquartile range) age 66.0 (14.0) years, 20.1% female, 52.3% rural status). Compared to NDD, SDD patients had less hyperlipidemia, atrial fibrillation, congestive heart failure, history of coronary artery bypass graft, and more radial access. SDD was noninferior to NDD for 30-day readmission but had a decreased 1-year (adjusted odds ratio [aOR]: 0.20, 95% confidence interval [CI]: 0.05-0.81, p = 0.024) and 5-year (aOR: 0.43, 95% CI: 0.28-0.66, p < 0.001) all-cause mortality compared to NDD. Rural status did not predict outcomes. CONCLUSIONS: SDD in patients in rural areas does not have a significantly higher rate of 30-day readmission. SDD patients had lower odds of 1- and 5-year mortality when compared to NDD. Future studies prospectively evaluating the safety of SDD in this population are warranted.

Survival outcomes in veterans with hepatocellular carcinoma, with and without HIV infection.

BACKGROUND: HIV infection has been associated with survival disparities among persons with hepatocellular carcinoma (HCC). However, most studies examining survival do not control for provider (e.g. type of HCC treatment given) or individual-level factors (e.g. homelessness, substance use) that could impact survival. In this study, we evaluate the effect of HIV status on survival among persons with HCC, in a comprehensive model that accounts for key individual, provider, and systems-level factors. METHODS: We conducted a retrospective cohort study of persons with HIV (PWH) matched 1 : 1 to HIV-negative controls based on age and year of HCC diagnosis in the national Veterans Administration (VA) health system. The primary outcome was survival. We used Cox regression models to evaluate the effect of HIV status on risk of death. RESULTS: This cohort included 200 matched pairs diagnosed with HCC between 2009 and 2016. A total of 114 PWH (57.0%) and 115 HIV-negative patients (57.5%) received guideline-concordant therapy ( P  = 0.92). Median survival was 13.4 months [95% confidence interval (CI) 8.7-18.1] among PWH and 19.1 months (95% CI 14.6-24.9) for HIV-negative patients. In adjusted models, older age, homelessness, advanced Barcelona Clinic Liver Cancer (BCLC) stage, and not receiving any HCC treatment predicted risk of death. HIV status was not associated with risk of death [adjusted hazard ratio (aHR) 0.95; 95% CI 0.75-1.20; P  = 0.65]. CONCLUSION: HIV status was not associated with worse survival among HCC patients, in a single-payer, equal access healthcare system. These results suggest that HIV infection alone should not exclude PWH from receiving standard therapy.

A Review of Current Trends on Polyvinyl Alcohol (PVA)-Based Solid Polymer Electrolytes.

Presently, the rising concerns about the fossil fuel crisis and ecological deterioration have greatly affected the world economy and hence have attracted attention to the utilization of renewable energies. Among the renewable energy being developed, supercapacitors hold great promise in broad applications such as electric vehicles. Presently, the main challenge facing supercapacitors is the amount of energy stored. This, however, does not satisfy the increasing demand for higher energy storage devices, and therefore, intensive research is being undertaken to overcome the challenges of low energy density. The purpose of this review is to report on solid polymer electrolytes (SPEs) based on polyvinyl alcohol (PVA). The review discussed the PVA as a host polymer in SPEs followed by a discussion on the influence of conducting salts. The formation of SPEs as well as the ion transport mechanism in PVA SPEs were discussed. The application and development of PVA-based polymer electrolytes on supercapacitors and other energy storage devices were elucidated. The fundamentals of electrochemical characterization for analyzing the mechanism of supercapacitor applications, such as EIS, LSV and dielectric constant, are highlighted. Similarly, thermodynamic transport models of ions and their mechanism about temperature based on Arrhenius and Vogel-Tammann-Fulcher (VTF) are analyzed. Methods for enhancing the electrochemical performance of PVA-based SPEs were reported. Likely challenges facing the current electrolytes are well discussed. Finally, research directions to overcome the present challenges in producing SPEs are proposed. Therefore, this review is expected to be source material for other researchers concerned with the development of PVA-based SPE material.

Derivation and Validation of a Clinical Risk Assessment Model for Cancer-Associated Thrombosis in Two Unique US Health Care Systems.

PURPOSE: Venous thromboembolism (VTE), especially pulmonary embolism (PE) and lower extremity deep vein thrombosis (LE-DVT), is a serious and potentially preventable complication for patients with cancer undergoing systemic therapy. METHODS: Using retrospective data from patients diagnosed with incident cancer from 2011-2020, we derived a parsimonious risk assessment model (RAM) using least absolute shrinkage and selection operator regression from the Harris Health System (HHS, n = 9,769) and externally validated it using the Veterans Affairs (VA) health care system (n = 79,517). Bootstrapped c statistics and calibration curves were used to assess external model discrimination and fit. Dichotomized risk strata using integer scores were created and compared against the Khorana score (KS). RESULTS: Incident VTE and PE/LE-DVT at 6 months occurred in 590 (6.2%) and 437 (4.6%) patients in HHS and 4,027 (5.1%) and 3,331 (4.2%) patients in the VA health care system. Assessed at the time of systemic therapy initiation, the new RAM included components of the KS with the modified cancer subtype, cancer staging, systemic therapy class, history of VTE, history of paralysis/immobility, recent hospitalization, and Asian/Pacific Islander race. The c statistic was 0.71 in HHS and 0.68 in the VA health care system (compared with 0.65 and 0.60, respectively, for KS). Furthermore, the new RAM appropriately reclassified 28% of patients and increased the proportion of VTEs in the high-risk group from 37% to 68% in the validation data set. CONCLUSION: The novel RAM stratified patients with cancer into a high-risk group with 8%-10% cumulative incidence of VTE and 7% PE/LE-DVT at 6 months (v 3% and 2%, respectively, in the low-risk group). The model had improved performance over the original KS and doubled the number of VTE events in the high-risk stratum. We encourage additional external validation from prospective studies.[Media: see text].

Investigating the prevalence of low energy availability, disordered eating and eating disorders in competitive and recreational female endurance runners.

Eating disorders (ED), disordered eating (DE) and low energy availability (LEA) can be detrimental to health and performance. Previous studies have independently investigated the prevalence of ED, DE or LEA; however, limited studies have combined methods identifying risk within female runners. The aim of this study was to identify the prevalence of ED, DE and LEA in United Kingdom-based female runners and associations between age, competition level and running distance. The Female Athlete Screening Tool (FAST) and Low Energy Availability in Females Questionnaire (LEAF-Q) were used in a cross-sectional study design. A total of n = 524 responses eligible for analysis were received. A total of n = 248 (47.3%), n = 209 (40%) and n = 49 (9.4%) athletes were at risk of LEA, DE and ED, respectively. LEAF-Q scores differed based upon age (Age: H(3) = 23.998, p ≤ .05) and competitive level (Comp: H(1) = 7.682, p ≤ .05) whereas FAST scores differed based on age (Age: F(3,523) = 4.753, p ≤ .05). Tukey's post-hoc tests showed significantly higher FAST scores in 18-24 years compared to all other age categories (p ≤ .05). Stepwise multiple regression demonstrated age and competitive level modestly predicted LEAF-Q scores (R2adj = 0.047, F(2,523) = 13.993, p ≤ .05, VIF = 1.0) whereas age modestly predicted FAST scores (R2adj = 0.022, F(1,523) = 12.711, p ≤ .05, VIF = 1.0). These findings suggest early identification, suitable screening methods and educational intervention programmes should be aimed at all levels of female endurance runners.Highlights A total of 524 female endurance completed a self-administered, online questionnaire screening for low energy availability, disordered eating and eating disorders risk.Age and competitive level modestly predicted low energy availability and age modestly predicted disordered eating and eating disorders in female endurance runners.A higher percentage of 18- to 24-year-old female endurance runners were at greater risk of low energy availability, disordered eating and eating disorders compared to other age categories.These findings highlight the need for regular screening in order to aid early interventions to prevent potential decrements in performance and health as endurance runners mature.

Retrorectus mesh reinforcement of ileostomy site fascial closure: stoma closure and reinforcement (SCAR) trial phase I/II results.

PURPOSE: Loop ileostomy (LI) is commonly employed during colorectal surgeries to reduce the consequences of anastomotic leak. Unfortunately, LI is associated with a 10-30% incisional hernia (IH) rate after closure. We hypothesized that prophylactic mesh reinforcement during LI takedown would safely prevent subsequent IH formation. METHODS: This single-center, phase I/II prospective study evaluated adult patients undergoing LI closure after left-sided colorectal cancer procedures. After LI closure, the posterior rectus sheath was mobilized and reapproximated with absorbable suture. A reduced-weight, macroporous, polypropylene mesh (Softmesh, BD) was placed in the retrorectus position to allow 3 cm of overlap and secured with fibrin sealant. The anterior fascia was closed with slowly absorbable suture. CT images obtained for cancer surveillance were reviewed by a radiologist blinded to the study intervention to evaluate for evidence of hernia or surgical site occurrence (SSO). RESULTS: Twenty patients were included with mean defect and mesh sizes of 11.2 cm2 and 64.2 cm2, respectively. Mean operative time for LI takedown and mesh augmented closure was 84 min with mesh implantation time being 16.4 min. Two patients were readmitted within 30 days for ileus, no patient required procedural intervention. Over a mean follow-up period of 20 ± 7 months, no SSO or hernias were observed clinically or on CT imaging. CONCLUSION: In our small series, retromuscular mesh reinforcement of LI closure appears feasible, safe and effective. This mesh reinforcement approach should be further investigated to evaluate its long-term effectiveness.

Characterization of Lymphocyte Subsets in Lymph Node and Spleen Sections in Fatal Pediatric Malaria.

Secondary lymphoid tissues play a major role in the human immune response to P. falciparum infection. Previous studies have shown that acute falciparum malaria is associated with marked perturbations of the cellular immune system characterized by lowered frequency and absolute number of circulating T cell subsets. A temporary relocation of T cells, possibly by infiltration to secondary lymphoid tissue, or their permanent loss through apoptosis, are two proposed explanations for this observation. We conducted the present study to determine the phenotype of lymphocyte subsets that accumulate in the lymph node and spleen during acute stages of falciparum malaria infection in Malawian children, and to test the hypothesis that lymphocytes are relocated to lymphoid tissues during acute infection. We stained tissue sections from children who had died of the two common clinical forms of severe malaria in Malawi, namely severe malarial anemia (SMA, n = 1) and cerebral malaria (CM, n = 3), and used tissue sections from pediatric patients who had died of non-malaria sepsis (n = 2) as controls. Both lymph node and spleen tissue (red pulp) sections from CM patients had higher percentages of T cells (CD4+ and CD8+) compared to the SMA patient. In the latter, we observed a higher percentage of CD20+ B cells in the lymph nodes compared to CM patients, whereas the opposite was observed in the spleen. Both lymph node and spleen sections from CM patients had increased percentages of CD69+ and CD45RO+ cells compared to tissue sections from the SMA patient. These results support the hypothesis that the relocation of lymphocytes to spleen and lymph node may contribute to the pan-lymphopenia observed in acute CM.

Cereal grain mineral micronutrient and soil chemistry data from GeoNutrition surveys in Ethiopia and Malawi.

The dataset comprises primary data for the concentration of 29 mineral micronutrients in cereal grains and up to 84 soil chemistry properties from GeoNutrition project surveys in Ethiopia and Malawi. The work provided insights on geospatial variation in the micronutrient concentration in staple crops, and the potential influencing soil factors. In Ethiopia, sampling was conducted in Amhara, Oromia, and Tigray regions, during the late-2017 and late-2018 harvest seasons. In Malawi, national-scale sampling was conducted during the April-June 2018 harvest season. The concentrations of micronutrients in grain were measured using inductively coupled plasma mass spectrometry (ICP-MS). Soil chemistry properties reported include soil pH; total soil nitrogen; total soil carbon (C); soil organic C; effective cation exchange capacity and exchangeable cations; a three-step sequential extraction scheme for the fractionation of sulfur and selenium; available phosphate; diethylenetriaminepentaacetic acid (DTPA)-extractable trace elements; extractable trace elements using 0.01 M Ca(NO3)2 and 0.01 M CaCl2; and isotopically exchangeable Zn. These data are reported here according to FAIR data principles to enable users to further explore agriculture-nutrition linkages.

International consensus conference recommendations on ultrasound education for undergraduate medical students.

OBJECTIVES: The purpose of this study is to provide expert consensus recommendations to establish a global ultrasound curriculum for undergraduate medical students. METHODS: 64 multi-disciplinary ultrasound experts from 16 countries, 50 multi-disciplinary ultrasound consultants, and 21 medical students and residents contributed to these recommendations. A modified Delphi consensus method was used that included a systematic literature search, evaluation of the quality of literature by the GRADE system, and the RAND appropriateness method for panel judgment and consensus decisions. The process included four in-person international discussion sessions and two rounds of online voting. RESULTS: A total of 332 consensus conference statements in four curricular domains were considered: (1) curricular scope (4 statements), (2) curricular rationale (10 statements), (3) curricular characteristics (14 statements), and (4) curricular content (304 statements). Of these 332 statements, 145 were recommended, 126 were strongly recommended, and 61 were not recommended. Important aspects of an undergraduate ultrasound curriculum identified include curricular integration across the basic and clinical sciences and a competency and entrustable professional activity-based model. The curriculum should form the foundation of a life-long continuum of ultrasound education that prepares students for advanced training and patient care. In addition, the curriculum should complement and support the medical school curriculum as a whole with enhanced understanding of anatomy, physiology, pathophysiological processes and clinical practice without displacing other important undergraduate learning. The content of the curriculum should be appropriate for the medical student level of training, evidence and expert opinion based, and include ongoing collaborative research and development to ensure optimum educational value and patient care. CONCLUSIONS: The international consensus conference has provided the first comprehensive document of recommendations for a basic ultrasound curriculum. The document reflects the opinion of a diverse and representative group of international expert ultrasound practitioners, educators, and learners. These recommendations can standardize undergraduate medical student ultrasound education while serving as a basis for additional research in medical education and the application of ultrasound in clinical practice.

The structure of EXTL3 helps to explain the different roles of bi-domain exostosins in heparan sulfate synthesis.

Heparan sulfate is a highly modified O-linked glycan that performs diverse physiological roles in animal tissues. Though quickly modified, it is initially synthesised as a polysaccharide of alternating ß-D-glucuronosyl and N-acetyl-α-D-glucosaminyl residues by exostosins. These enzymes generally possess two glycosyltransferase domains (GT47 and GT64)-each thought to add one type of monosaccharide unit to the backbone. Although previous structures of murine exostosin-like 2 (EXTL2) provide insight into the GT64 domain, the rest of the bi-domain architecture is yet to be characterised; hence, how the two domains co-operate is unknown. Here, we report the structure of human exostosin-like 3 (EXTL3) in apo and UDP-bound forms. We explain the ineffectiveness of EXTL3's GT47 domain to transfer ß-D-glucuronosyl units, and we observe that, in general, the bi-domain architecture would preclude a processive mechanism of backbone extension. We therefore propose that heparan sulfate backbone polymerisation occurs by a simple dissociative mechanism.

Surgery or active surveillance for pNETs < 2 cm: Preliminary results from a single center Brazilian cohort.

BACKGROUND AND OBJECTIVES: Incidence of pancreatic neuroendocrine tumors (pNETS) seems to be rising over the years, with many cases incidentally diagnosed. Surgery and active surveillance are current treatment modalities for small pNETS. We review our institutional series and compare outcomes for small asymptomatic and nonfunctioning tumors. METHODS: This retrospective cohort study included patients with 2 cm or less and well differentiated pNETS at a single Brazilian Cancer Center. From 2002 to 2020, patients received active surveillance or surgery as a treatment strategy. Short and long-term results were compared. RESULTS: Sixty-four patients were included, 41 in surgical strategy and 23 in the active surveillance approach. Baseline group characteristics were comparable. More patients on active surveillance underwent abdominal magnetic resonance imaging (MRI) and had tumors located in the pancreatic head (41% vs. 17%, p = 0.038). Minimally invasive procedure was chosen in 80.1% of the surgical patients. No patient died after surgery. Median follow-up period was 38.6 and 46.4 months for active surveillance and surgery cohorts, respectively. No difference in disease progression rate was observed. CONCLUSION: Both approaches seem to be safe for small pNETs. Long-term outcome and quality of life should be considered when discussing such options with patients.