Mitotic bookmarking by transcription factors: be aware of redundancy.

A recent report by Chervova, Molliex, et al. shows redundant functions for the transcription factors (TFs) ESRRB and NR5A2 as mitotic bookmarkers in mouse embryonic stem (ES) cells. These occupy some of their target sites in mitotic chromatin, ensuring their robust reactivation after cell division, including markers and regulators of pluripotency.

COVID-19-related hyperglycemia is associated with infection of hepatocytes and stimulation of gluconeogenesis.

Occurrence of hyperglycemia upon infection is associated with worse clinical outcome in COVID-19 patients. However, it is still unknown whether SARS-CoV-2 directly triggers hyperglycemia. Herein, we interrogated whether and how SARS-CoV-2 causes hyperglycemia by infecting hepatocytes and increasing glucose production. We performed a retrospective cohort study including patients that were admitted at a hospital with suspicion of COVID-19. Clinical and laboratory data were collected from the chart records and daily blood glucose values were analyzed to test the hypothesis on whether COVID-19 was independently associated with hyperglycemia. Blood glucose was collected from a subgroup of nondiabetic patients to assess pancreatic hormones. Postmortem liver biopsies were collected to assess the presence of SARS-CoV-2 and its transporters in hepatocytes. In human hepatocytes, we studied the mechanistic bases of SARS-CoV-2 entrance and its gluconeogenic effect. SARS-CoV-2 infection was independently associated with hyperglycemia, regardless of diabetic history and beta cell function. We detected replicating viruses in human hepatocytes from postmortem liver biopsies and in primary hepatocytes. We found that SARS-CoV-2 variants infected human hepatocytes in vitro with different susceptibility. SARS-CoV-2 infection in hepatocytes yields the release of new infectious viral particles, though not causing cell damage. We showed that infected hepatocytes increase glucose production and this is associated with induction of PEPCK activity. Furthermore, our results demonstrate that SARS-CoV-2 entry in hepatocytes occurs partially through ACE2- and GRP78-dependent mechanisms. SARS-CoV-2 infects and replicates in hepatocytes and exerts a PEPCK-dependent gluconeogenic effect in these cells that potentially is a key cause of hyperglycemia in infected patients.

SEDA 2024 update: enhancing the SEquence DAtaset builder for seamless integration into automated data analysis pipelines.

BACKGROUND: The initial version of SEDA assists life science researchers without programming skills with the preparation of DNA and protein sequence FASTA files for multiple bioinformatics applications. However, the initial version of SEDA lacks a command-line interface for more advanced users and does not allow the creation of automated analysis pipelines. RESULTS: The present paper discusses the updates of the new SEDA release, including the addition of a complete command-line interface, new functionalities like gene annotation, a framework for automated pipelines, and improved integration in Linux environments. CONCLUSION: SEDA is an open-source Java application and can be installed using the different distributions available ( https://www.sing-group.org/seda/download.html ) as well as through a Docker image ( https://hub.docker.com/r/pegi3s/seda ). It is released under a GPL-3.0 license, and its source code is publicly accessible on GitHub ( https://github.com/sing-group/seda ). The software version at the time of submission is archived at Zenodo (version v1.6.0, http://doi.org/10.5281/zenodo.10201605 ).

Antimalarial resistance risk in Mozambique detected by a novel quadruplex droplet digital PCR assay.

While the Plasmodium falciparum malaria parasite continues to cause severe disease globally, Mozambique is disproportionally represented in malaria case totals. Acquisition of copy number variations (CNVs) in the parasite genome contributes to antimalarial drug resistance through overexpression of drug targets. Of interest, piperaquine resistance is associated with plasmepsin 2 and 3 CNVs (pfpmp2 and pfpmp3, respectively), while CNVs in the multidrug efflux pump, multidrug resistance-1 (pfmdr1), increase resistance to amodiaquine and lumefantrine. These antimalarials are partner drugs in artemisinin combination therapies (ACTs) and therefore, CNV detection with accurate and efficient tools is necessary to track ACT resistance risk. Here, we evaluated ~300 clinically derived samples collected from three sites in Mozambique for resistance-associated CNVs. We developed a novel, medium-throughput, quadruplex droplet digital PCR (ddPCR) assay to simultaneously quantify the copy number of pfpmp3, pfpmp2, and pfmdr1 loci in these clinical samples. By using DNA from laboratory parasite lines, we show that this nanodroplet-based method is capable of detecting picogram levels of parasite DNA, which facilitates its application for low yield and human host-contaminated clinical surveillance samples. Following ddPCR and the application of quality control standards, we detected CNVs in 13 of 229 high-quality samples (prevalence of 5.7%). Overall, our study revealed a low number of resistance CNVs present in the parasite population across all three collection sites, including various combinations of pfmdr1, pfpmp2, and pfpmp3 CNVs. The potential for future ACT resistance across Mozambique emphasizes the need for continued molecular surveillance across the region.

BUB1B monoallelic germline variants contribute to prostate cancer predisposition by triggering chromosomal instability.

BACKGROUND: Prostate cancer (PrCa) is the most frequently diagnosed cancer in men. Variants in known moderate- to high-penetrance genes explain less than 5% of the cases arising at early-onset (< 56 years) and/or with familial aggregation of the disease. Considering that BubR1 is an essential component of the mitotic spindle assembly checkpoint, we hypothesized that monoallelic BUB1B variants could be sufficient to fuel chromosomal instability (CIN), potentially triggering (prostate) carcinogenesis. METHODS: To unveil BUB1B as a new PrCa predisposing gene, we performed targeted next-generation sequencing in germline DNA from 462 early-onset/familial PrCa patients and 1,416 cancer patients fulfilling criteria for genetic testing for other hereditary cancer syndromes. To explore the pan-cancer role of BUB1B, we used in silico BubR1 molecular modeling, in vitro gene-editing, and ex vivo patients' tumors and peripheral blood lymphocytes. RESULTS: Rare BUB1B variants were found in ~ 1.9% of the early-onset/familial PrCa cases and in ~ 0.6% of other cancer patients fulfilling criteria for hereditary disease. We further show that BUB1B variants lead to decreased BubR1 expression and/or stability, which promotes increased premature chromatid separation and, consequently, triggers CIN, driving resistance to Taxol-based therapies. CONCLUSIONS: Our study shows that different BUB1B variants may uncover a trigger for CIN-driven carcinogenesis, supporting the role of BUB1B as a (pan)-cancer predisposing gene with potential impact on genetic counseling and treatment decision-making.

The first multi-tissue genome-scale metabolic model of a woody plant highlights suberin biosynthesis pathways in Quercus suber.

Over the last decade, genome-scale metabolic models have been increasingly used to study plant metabolic behaviour at the tissue and multi-tissue level under different environmental conditions. Quercus suber, also known as the cork oak tree, is one of the most important forest communities of the Mediterranean/Iberian region. In this work, we present the genome-scale metabolic model of the Q. suber (iEC7871). The metabolic model comprises 7871 genes, 6231 reactions, and 6481 metabolites across eight compartments. Transcriptomics data was integrated into the model to obtain tissue-specific models for the leaf, inner bark, and phellogen, with specific biomass compositions. The tissue-specific models were merged into a diel multi-tissue metabolic model to predict interactions among the three tissues at the light and dark phases. The metabolic models were also used to analyse the pathways associated with the synthesis of suberin monomers, namely the acyl-lipids, phenylpropanoids, isoprenoids, and flavonoids production. The models developed in this work provide a systematic overview of the metabolism of Q. suber, including its secondary metabolism pathways and cork formation.

Coral Reef Aorta: Literature Review and Analysis of the Published Cases in the Last 20 Years.

BACKGROUND: Coral reef aorta (CRA) is defined by the presence of heavily calcified exophytic plaques that protrude into the aortic lumen. However, the exact causes and development of this condition are still not fully understood. When the aortic branches are affected, it can result in various symptoms. Despite ongoing research, there is currently no established consensus on the best treatment for CRA. This review aims to examine the latest findings regarding the clinical presentation and approach to treating patients with CRA. METHODS: We conducted a systematic electronic search of the literature using the PubMed and Embase databases. Throughout the search, we adhered to the guidelines outlined in the PRISMA framework. From the identified publications, we extracted information pertaining to patients' characteristics, symptoms, and types of treatment from a total of 124 cases reported over the past 20 years. The primary focus of our analysis was to assess the improvement of signs and symptoms, as well as to evaluate any postoperative complications. To achieve this, we performed both descriptive and inferential analyses on the collected data. Additionally, we conducted subgroup analyses based on treatment types and symptoms observed at presentation, presenting the findings in the form of odds ratios (ORs). RESULTS: After removing duplicate articles, we carefully screened the titles of 67 retrieved articles and excluded those that did not align with the purpose of our study. Subsequently, we thoroughly analyzed the remaining 41 articles along with their references, ultimately including 29 studies that were deemed most relevant for our systematic review. We examined a total of 124 cases of patients diagnosed with CRA, comprising 77 (62.1%) females and 48 (38.7%) males, with a mean age of 59 years (range: 37-84). The predominant signs and symptoms observed were intermittent claudication, reported in 57 (46.0%) patients, followed by refractory hypertension in 45 (36.3%) patients, intestinal angina in 28 (22.6%) patients, and renal insufficiency in 15 (12.1%) patients. Among the treated patients, 110 (88.7%) underwent open surgery repair (OSR), 11 (8.9%) received endovascular treatment, and 3 (2.4%) underwent laparoscopy. Postoperatively, a significant number of patients experienced substantial relief or complete resolution of their symptoms, as well as improved control of hypertension and renal function. In the group of patients treated with OSR, the inhospital stay mortality rate was 10.9%, the morbidity rate was 28.2%, and the reintervention rate was 15.5%. The high mortality rate during hospital stays in this group may be associated with such invasive procedures performed on patients who have substantial cardiovascular burden and multiple comorbidities. Conversely, no postoperative complications were reported in the group of patients treated with endovascular procedures or laparoscopic surgery. CONCLUSIONS: While coral reef aorta (CRA) is considered a rare condition, it is crucial for the medical community to remain vigilant about its diagnosis, particularly in patients presenting with symptoms such as intermittent claudication, refractory hypertension, renal impairment, or intestinal angina. Based on the findings of this review, both OSR and endovascular treatment have shown promise as viable therapeutic options. Although endovascular therapies may not always be feasible or may have reduced durability in these calcified bulky lesions, they should be considered in patients with multiple comorbidities, due to the high postoperative mortality rates associated with more invasive approaches. Additionally, these endoluminal procedures have demonstrated good patency rates during the 18-month follow-up period. It is essential to emphasize that the treatment strategy should be determined on a case-by-case basis, involving a multidisciplinary team to tailor it to the specific needs of each individual patient.

Thoracic aortic aneurysms, a single center's 10-years experience and analysis of outcomes.

INTRODUCTION: Thoracic aortic aneurysms (TAAs) are an increasingly prevalent pathology with significant associated morbidity and mortality. Thoracic endovascular aortic repair (TEVAR) is the primary line of treatment. The purpose of this study was to analyse a single center's experience in the treatment of TAAs and identify possible risk factors for worse outcomes. METHODS: A retrospective review of our institutional database was done to identify all patients treated for TAAs in a 10-year period, from 1 January 2012 to 31 December 2022. Data were extracted from patients' medical records. Primary outcome was all-cause mortality and secondary outcomes were procedure related morbidity (vascular access complications, medullary ischaemia, stroke, endoleaks, migration, aneurysm sac enlargement >5 mm) and need for reintervention at 1-, 6- and 12-month follow-up. A descriptive and inferential analysis of the data was performed. Statistical analyses were conducted using the IBM Statistical Package for Social Sciences (SPSS) software. RESULTS: We identified 34 patients treated for TAAs in this period. Mean age was 68 years [47-87] and 79.4% of patients were male. Mean aneurysm diameter was 63 mm [35-100], 55.9% fusiform and 44.1% saccular. The majority (91.2%) were located at the descending thoracic aorta and 3 (8.8%) of them extended to the aortic arch. The most common aetiology was degenerative in 22 patients (64.7%), followed by aortic dissection in 8 patients (23.5%). Elective surgery was performed in 19 (61.3%) patients and 12 (38.7%) had urgent repair. TEVAR was the treatment of choice in 24 (77.4%) patients, and the remaining 7 (22.6%) were treated with hybrid surgery. Mean length of hospital stay was 10 days [2-80] (6 days for elective repair versus 16 days for urgent repair, p = .016). Follow-up period ranged from 1 month to 10 years. At 1 year follow-up, all-cause mortality was 15%, morbidity was 30% (with 6 (22%) patients having a type Ia endoleak) and need for reintervention was 22%. Aneurysm diameter was a significant risk factor for procedure related morbidity (median diameter of 73.5 mm versus 56.0 mm in patients with no morbidity; p = .027). The presence of type Ia endoleak was significantly associated with higher reintervention rates (p = .001), but not with higher mortality rates (p = .515). Age, female sex, aetiology and urgent repair weren't associated with any significant differences in the outcomes. CONCLUSIONS: TEVAR proved to be effective in the treatment of TAAs, with good outcomes at short and mid-term follow-up. TAAs should be diagnosed earlier and be promptly treated when meeting criteria to prevent worse outcomes.

Impact of Age and of the Patent Ductus Arteriosus on Pulmonary Hemodynamics in Children with Complete Atrioventricular Septal Defect.

Complete atrioventricular septal defect (CAVSD) can lead to the development of pulmonary obstructive vascular disease due to high pulmonary blood flow and pressures. This study aimed to evaluate the changes in pulmonary hemodynamics with aging and with patent ductus arteriosus (PDA) in children with CAVSD. We retrospectively evaluated 137 children (94% with trisomy 21, median age of 195 (25-2963) days, 58.4% female) with CASVD referred to cardiac catheterization from January 2000 to December 2020. Those with associated congenital heart disease, except PDA, had been excluded. They were divided into three age terciles (T1, T2, and T3). Aging was directly associated with higher mean (T1: 34.2 ± 9.1; T2: 37.1 ± 5.8; T3: 42 ± 10.6 mmHg, p < 0.001) and diastolic (T1: 19.4 ± 5.3; T2 21.6 ± 5.0; T3: 26.0 ± 9.5 mmHg, P < 0.001) pulmonary arterial pressures, and with higher pulmonary vascular resistance (T1: 3.24 ± 1.69, T2: 3.47 ± 1.19; T3: 4.49 ± 3.91 Wu.m2, p = 0.023). This resulted in a loss of eligibility for anatomical correction, which became evident only after 300 days of age. PDA was associated with a higher mean (37.2 [35.9; 38.5] vs. 41.3 [37.5; 45.0] mmHg, p = 0.049) and diastolic (21.7 [20.7; 22.6] vs. 26.4 [24.1; 29.0] mmHg, p = 0.001) pulmonary pressure, and resistor-compliance time (0.28 [0.26; 0.29] vs. 0.36 [0.31; 0.40], p = 0.001) after adjusting for age and sex. In children with CAVSD, aging was associated with worsening of pulmonary vascular hemodynamics, particularly when PDA was associated, resulting in loss of eligibility for anatomical correction after 10 months of age as the first surgical option.

Intraoperative Angle Measurement of Anatomical Structures: A Systematic Review.

Ensuring precise angle measurement during surgical correction of orientation-related deformities is crucial for optimal postoperative outcomes, yet there is a lack of an ideal commercial solution. Current measurement sensors and instrumentation have limitations that make their use context-specific, demanding a methodical evaluation of the field. A systematic review was carried out in March 2023. Studies reporting technologies and validation methods for intraoperative angular measurement of anatomical structures were analyzed. A total of 32 studies were included, 17 focused on image-based technologies (6 fluoroscopy, 4 camera-based tracking, and 7 CT-based), while 15 explored non-image-based technologies (6 manual instruments and 9 inertial sensor-based instruments). Image-based technologies offer better accuracy and 3D capabilities but pose challenges like additional equipment, increased radiation exposure, time, and cost. Non-image-based technologies are cost-effective but may be influenced by the surgeon's perception and require careful calibration. Nevertheless, the choice of the proper technology should take into consideration the influence of the expected error in the surgery, surgery type, and radiation dose limit. This comprehensive review serves as a valuable guide for surgeons seeking precise angle measurements intraoperatively. It not only explores the performance and application of existing technologies but also aids in the future development of innovative solutions.

Effects of pasture management and supplementation on the productive performance of recently lambed ewes.

The hypothesis was tested that the performance of lactating ewes is affected by the supplementation level and pasture management. Two supplementation levels (0.5 and 1.0% of body weight, BW) and two pasture managements (mowed and non-mowed) were tested. Forty adult ewes (2 years old) with an average weight at lambing of 62.97 ± 7.0 kg (day 0) and an average the body condition score of 2.5 points (day 0) were evaluated. Verminosis was monitored with periodic deworming. The number of eggs per gram of feces (EPG) of ewes at lambing was used as a covariate for performance assessments. Ewes lost an average of 7.5 kg over the 90 days post-partum (12% BW). The weaning rate was 53%. The body condition of the ewes was influenced by the post-partum period. The ewes mobilized their body reserves in the first 30 days of lactation. Mowing management negatively affected the nutritive value of the forage. Supplementation with 0.5% BW was sufficient for nutritional management post-partum. Pasture management (mowed vs. not mowed) cannot prevent post-partum weight loss. Supplementation levels and pasture management altered the morphological and chemical components of the pasture.

Epithelial X-Box Binding Protein 1 Coordinates Tumor Protein p53-Driven DNA Damage Responses and Suppression of Intestinal Carcinogenesis.

BACKGROUND & AIMS: Throughout life, the intestinal epithelium undergoes constant self-renewal from intestinal stem cells. Together with genotoxic stressors and failing DNA repair, this self-renewal causes susceptibility toward malignant transformation. X-box binding protein 1 (XBP1) is a stress sensor involved in the unfolded protein response (UPR). We hypothesized that XBP1 acts as a signaling hub to regulate epithelial DNA damage responses. METHODS: Data from The Cancer Genome Atlas were analyzed for association of XBP1 with colorectal cancer (CRC) survival and molecular interactions between XBP1 and p53 pathway activity. The role of XBP1 in orchestrating p53-driven DNA damage response was tested in vitro in mouse models of chronic intestinal epithelial cell (IEC) DNA damage (Xbp1/H2bfl/fl, Xbp1ΔIEC, H2bΔIEC, H2b/Xbp1ΔIEC) and via orthotopic tumor organoid transplantation. Transcriptome analysis of intestinal organoids was performed to identify molecular targets of Xbp1-mediated DNA damage response. RESULTS: In The Cancer Genome Atlas data set of CRC, low XBP1 expression was significantly associated with poor overall survival and reduced p53 pathway activity. In vivo, H2b/Xbp1ΔIEC mice developed spontaneous intestinal carcinomas. Orthotopic tumor organoid transplantation revealed a metastatic potential of H2b/Xbp1ΔIEC-derived tumors. RNA sequencing of intestinal organoids (H2b/Xbp1fl/fl, H2bΔIEC, H2b/Xbp1ΔIEC, and H2b/p53ΔIEC) identified a transcriptional program downstream of p53, in which XBP1 directs DNA-damage-inducible transcript 4-like (Ddit4l) expression. DDIT4L inhibits mechanistic target of rapamycin-mediated phosphorylation of 4E-binding protein 1. Pharmacologic mechanistic target of rapamycin inhibition suppressed epithelial hyperproliferation via 4E-binding protein 1. CONCLUSIONS: Our data suggest a crucial role for XBP1 in coordinating epithelial DNA damage responses and stem cell function via a p53-DDIT4L-dependent feedback mechanism.

Anti-malarial resistance in Mozambique: Absence of Plasmodium falciparum Kelch 13 (K13) propeller domain polymorphisms associated with resistance to artemisinins.

BACKGROUND: Malaria remains one of the most serious public health problems in sub-Saharan Africa and Mozambique is the world's fourth largest contributor, with 4.7% of disease cases and 3.6% of total deaths due to malaria. Its control relies on the fight against the vector and treatment of confirmed cases with anti-malarial drugs. Molecular surveillance is an important tool for monitoring the spread of anti-malarial drug resistance. METHODS: A cross-sectional study recruited 450 participants with malaria infection detected by Rapid Diagnostic Tests, from three different study sites (Niassa, Manica and Maputo) between April and August 2021. Correspondent blood samples were collected on filter paper (Whatman® FTA® cards), parasite DNA extracted and pfk13 gene sequenced using Sanger method. SIFT software (Sorting Intolerant From Tolerant) was used, predict whether an amino acid substitution affects protein function. RESULTS: No pfkelch13-mediated artemisinin resistance gene mutation was detected in this study settings. However, non-synonymous mutations were detected at prevalence of 10.2%, 6% and 5% in Niassa, Manica and Maputo, respectively. Most (56.3%) of the reported non-synonymous mutations were due to substitution at the first base of the codon, 25% at the second base and 18.8% at the third base. Additionally, 50% of non-synonymous mutations showed a SIFTscore bellow cut off value of 0.05, therefore, they were predicted to be deleterious. CONCLUSION: These results do not show an emergence of artemisinin resistance cases in Mozambique. However, the increased number of novel non-synonymous mutations highlights the relevance of increasing the number of studies focused on the molecular surveillance of artemisinin resistance markers, for its early detection.

Best Medical Treatment in Patients with Asymptomatic Carotid Stenosis: Myth or Reality?

BACKGROUND: Approximately 1.4 million strokes/year causing about 1.1 million deaths annually occur in Europe and 10%-15% of those strokes are result of thromboembolism from a previously significant asymptomatic carotid stenosis (ACS). Medical treatment has improved considerably in the last 15 years; however, its success depends on patient compliance. The aim of our study was to evaluate, in patients with ACS, the implementation and patient adherence to best medical treatment (BMT). Additionally, we sought to determine the "real-world" incidence of cerebrovascular/coronary events in a cohort of nonoperated ACS patients and weighing this risk against surgical complications in patients with ACS undergoing surgical treatment at our Department. METHODS: Patients with ACS ≥ 60% identified by a carotid ultrasound performed at our Department were retrospectively evaluated. Patients selected to BMT were excluded if the follow-up period was inferior to 2 years, as well as patients lost in follow-up, with missing clinical information and submitted to carotid stenting. Patients' data collection was supported by hospital reporting system and data were introduced into a database created for the purpose. Statistical analysis was performed using SPSS-25 software. RESULTS: After exclusion criteria were applied, the last 120 consecutive patients (60 with ACS submitted do carotid endarterectomy and 60 with ACS under BMT) were retrospectively evaluated. Twenty one patients had ipsilateral events for more than 6 months. Most patients had hypertension (n = 107; 89%), dyslipidemia (n = 101; 84%), 40% had diabetes, 33% diagnosed coronary disease, 32% were overweight or obese, and 17% were current smokers. Blood pressure control, normal weight, statin with/without ezetimibe association, and antiaggregant therapy were only achieved in 33 patients and only 5 had additionally low-density lipoprotein levels < 70 mg/dL, hemoglobin A1c < 7%, and were nonsmokers. Of the 60 patients assigned to medical treatment, 3 (5%) had a stroke at 2 years of follow-up, which was fatal in 1 patient. Among patients submitted to carotid endarterectomy, perioperative stroke was documented in 3% of the patients, none of them disabling or fatal. CONCLUSIONS: Although some recent studies report a risk of ipsilateral stroke of only 0.34% per year in patients with ACS ≥ 50% under BMT therapy in our everyday practice strict compliance to medical treatment fails in most patients. In consequence, we think that a "one-size-fits-all" guideline policy may not be appropriate for all patients and the management of specific ACS patients may need to be individualized.

Indian food habit & food ingredients may have a role in lowering the severity & high death rate from COVID-19 in Indians: findings from the first nutrigenomic analysis.

Background & objectives: During the COVID-19 pandemic, the death rate was reportedly 5-8 fold lower in India which is densely populated as compared to less populated western countries. The aim of this study was to investigate whether dietary habits were associated with the variations in COVID-19 severity and deaths between western and Indian population at the nutrigenomics level. Methods: In this study nutrigenomics approach was applied. Blood transcriptome of severe COVID-19 patients from three western countries (showing high fatality) and two datasets from Indian patients were used. Gene set enrichment analyses were performed for pathways, metabolites, nutrients, etc., and compared for western and Indian samples to identify the food- and nutrient-related factors, which may be associated with COVID-19 severity. Data on the daily consumption of twelve key food components across four countries were collected and a correlation between nutrigenomics analyses and per capita daily dietary intake was investigated. Results: Distinct dietary habits of Indians were observed, which may be associated with low death rate from COVID-19. Increased consumption of red meat, dairy products and processed foods by western populations may increase the severity and death rate by activating cytokine storm-related pathways, intussusceptive angiogenesis, hypercapnia and enhancing blood glucose levels due to high contents of sphingolipids, palmitic acid and byproducts such as CO2 and lipopolysaccharide (LPS). Palmitic acid also induces ACE2 expression and increases the infection rate. Coffee and alcohol that are highly consumed in western countries may increase the severity and death rates from COVID-19 by deregulating blood iron, zinc and triglyceride levels. The components of Indian diets maintain high iron and zinc concentrations in blood and rich fibre in their foods may prevent CO2 and LPS-mediated COVID-19 severity. Regular consumption of tea by Indians maintains high high-density lipoprotein (HDL) and low triglyceride in blood as catechins in tea act as natural atorvastatin. Importantly, regular consumption of turmeric in daily food by Indians maintains strong immunity and curcumin in turmeric may prevent pathways and mechanisms associated with SARS-CoV-2 infection and COVID-19 severity and lowered the death rate. Interpretation & conclusions: Our results suggest that Indian food components suppress cytokine storm and various other severity related pathways of COVID-19 and may have a role in lowering severity and death rates from COVID-19 in India as compared to western populations. However, large multi-centered case-control studies are required to support our current findings.

Human-Robot Joint Misalignment, Physical Interaction, and Gait Kinematic Assessment in Ankle-Foot Orthoses.

Lower limb exoskeletons and orthoses have been increasingly used to assist the user during gait rehabilitation through torque transmission and motor stability. However, the physical human-robot interface (HRi) has not been properly addressed. Current orthoses lead to spurious forces at the HRi that cause adverse effects and high abandonment rates. This study aims to assess and compare, in a holistic approach, human-robot joint misalignment and gait kinematics in three fixation designs of ankle-foot orthoses (AFOs). These are AFOs with a frontal shin guard (F-AFO), lateral shin guard (L-AFO), and the ankle modulus of the H2 exoskeleton (H2-AFO). An experimental protocol was implemented to assess misalignment, fixation displacement, pressure interactions, user-perceived comfort, and gait kinematics during walking with the three AFOs. The F-AFO showed reduced vertical misalignment (peak of 1.37 ± 0.90 cm, p-value < 0.05), interactions (median pressures of 0.39-3.12 kPa), and higher user-perceived comfort (p-value < 0.05) when compared to H2-AFO (peak misalignment of 2.95 ± 0.64 and pressures ranging from 3.19 to 19.78 kPa). F-AFO also improves the L-AFO in pressure (median pressures ranging from 8.64 to 10.83 kPa) and comfort (p-value < 0.05). All AFOs significantly modified hip joint angle regarding control gait (p-value < 0.01), while the H2-AFO also affected knee joint angle (p-value < 0.01) and gait spatiotemporal parameters (p-value < 0.05). Overall, findings indicate that an AFO with a frontal shin guard and a sports shoe is effective at reducing misalignment and pressure at the HRI, increasing comfort with slight changes in gait kinematics.

Mathematical models to predict the lamb weight at birth and at weaning reared in the tropical warm-climate pasture.

Our objective was to evaluate the productive parameters of ewes and their lambs in relation to ewe age and to develop models for predicting lamb weight at birth and weaning in a tropical warm-climate pasture. Individual data were collected from 273 ewes and 273 lambs, between 2013 and 2021. During this period all animals were kept on pastures of Brachiaria brizantha cv. Marandu All lambs in the experiments were supplemented in creep-feeding. A descriptive statistical analysis was performed using the PROC SUMMARY procedure in SAS (SAS University Edition, SAS Institute Inc. Cary, CA, USA). Pearson correlation coefficients between variables were estimated using the PROC CORR procedure in SAS (SAS University Edition, SAS Institute Inc. Cary, CA, USA). Model adjustments and variable selection were performed using PROC REG in SAS (SAS University Edition, SAS Institute Inc. Cary, CA, USA). The STEPWISE option and Mallow's C(p) were used to select the variables included in the equations. Outliers were identified by evaluating the studentized residuals based on the predicted values from the equations. Residual analysis was predicted by regression minus observed values and those that fell outside the range of -2.5 to 2.5 were removed. Several statistics were used to assess the predictability of the equations, including the coefficients of determination (r2) and mean standard error (RMSE). The average ewe age at lambing was 3.4 ± 1.7 years, with an average weight of 56.9 ± 8,9 kg and average body condition score (BCS) of 2,4 ± 0.8 points. The average ewe age at weaning was 51.1 ± 7.9, with average BCS of 1.8 ± 0.8 points. The average lamb at birthing was 3.9 ± 0.9 kg. The average lamb at weaning was 21.0 ± 4.9, with daily gain of 0.2 ± 0.1 kg/day and total gain of 17.1 ± 4.7 kg birth to weaning. The lamb produced by ewe at lambing was 5.3 ± 1.7 kg/ewe. The lamb weaned by ewe at weaning was 28.7 ± 10.8 kg/ewe. The ratios of lamb produced per ewe at birth and at weaning were 0.1 ± 0.03 and 0.6 ± 0.2, respectively. The lamb's birth weight showed a positive linear relationship with the age of the ewe, increasing by 115 g per year of age. The regression equations adjusted for ewe age had maximum points ranging from 4.2 to 5.2, occurring at average age of 4,7 years. The other characteristics showed a quadratic tendency. The results suggest the culling of ewes at five years of age to generate lambs with ideal weight at birth and at weaning raised in warm tropical pastures.

Antioxidant action of yerba mate on carcass and meat characteristics and fatty acid profile in meat and fat of lambs finished in tropical pastures.

The objective was to evaluate the effect of the supplementation with natural antioxidants from Yerba mate (Ilex paraguariensis St. Hil.) on the performance, carcass and meat characteristics, and fatty acid profile in meat and fat of Texel × Ile de France lambs kept in Brachiaria-grass pasture. Twenty lambs with a mean age of 90 days and 26.3 kg of BW were distributed in a completely randomized design in two treatments with 10 replicates/treatment: Control-protein-energy supplement based on corn and soybean meal (150 g/kg DM of crude protein) without the addition of natural antioxidant yerba mate and Yerba Mate - energy protein supplement with the addition of yerba mate (110 g/kg DM). There was no treatment effect on animal performance and carcass characteristics. The subcutaneous fat thickness was significantly higher for lambs treated without yerba mate. There was no effect of nutritional treatments on the oxidative markers of lamb meat. The muscle of the animals treated with yerba mate showed a higher concentration of unsaturated and polyunsaturated fatty acids elaidic, linolenic, thymnodonic, docosadienoic, and ceorvonic. The fat of the animals treated with yerba mate showed a higher concentration of palmitoleic acid, linoelaidic acid, heneicosanoic acid, dihomo-γ-linolenic acid, and arachidonic acid. The concentration of polyunsaturated fatty acids was significantly higher in meat and fat of lambs treated with yerba mate. Including yerba mate in the diet of lambs kept on Brachiaria pastures improves the lipid profile of polyunsaturated fatty acids in meat and fat, without altering the performance of the animals.

The learning curve in bladder MRI using VI-RADS assessment score during an interactive dedicated training program.

OBJECTIVE: The purpose of the study was to evaluate the effect of an interactive training program on the learning curve of radiology residents for bladder MRI interpretation using the VI-RADS score. METHODS: Three radiology residents with minimal experience in bladder MRI served as readers. They blindly evaluated 200 studies divided into 4 subsets of 50 cases over a 3-month period. After 2 months, the first subset was reassessed, resulting in a total of 250 evaluations. An interactive training program was provided and included educational lessons and case-based practice. The learning curve was constructed by plotting mean agreement as the ratio of correct evaluations per batch. Inter-reader agreement and diagnostic performance analysis were performed with kappa statistics and ROC analysis. RESULTS: As for the VI-RADS scoring agreement, the kappa differences between pre-training and post-training evaluation of the same group of cases were 0.555 to 0.852 for reader 1, 0.522 to 0.695 for reader 2, and 0.481 to 0.794 for reader 3. Using VI-RADS ≥ 3 as cut-off for muscle invasion, sensitivity ranged from 84 to 89% and specificity from 91 to 94%, while the AUCs from 0.89 (95% CI:0.84, 0.94) to 0.90 (95% CI:0.86, 0.95). Mean evaluation time decreased from 5.21 ± 1.12 to 3.52 ± 0.69 min in subsets 1 and 5. Mean grade of confidence improved from 3.31 ± 0.93 to 4.21 ± 0.69, in subsets 1 and 5. CONCLUSION: An interactive dedicated education program on bladder MRI and the VI-RADS score led to a significant increase in readers' diagnostic performance over time, with a general improvement observed after 100-150 cases. KEY POINTS: • After the first educational lesson and 100 cases were interpreted, the concordance on VI-RADS scoring between the residents and the experienced radiologist was significantly higher. • An increase in the grade of confidence was experienced after 100 cases. • We found a decrease in the evaluation time after 150 cases.