Using high-density SNP data to unravel the origin of the Franches-Montagnes horse breed.

BACKGROUND The Franches-Montagnes (FM) is the last native horse breed of Switzerland, established at the end of the 19th century by cross-breeding local mares with Anglo-Norman stallions. We collected high-density SNP genotype data (Axiom™ 670 K Equine genotyping array) from 522 FM horses, including 44 old-type horses (OF), 514 European Warmblood horses (WB) from Sweden and Switzerland (including a stallion used for cross-breeding in 1990), 136 purebred Arabians (AR), 32 Shagya Arabians (SA), and 64 Thoroughbred (TB) horses, as introgressed WB stallions showed TB origin in their pedigrees. The aim of the study was to ascertain fine-scale population structures of the FM breed, including estimation of individual admixture levels and genomic inbreeding (FROH) by means of Runs of Homozygosity. RESULTS To assess fine-scale population structures within the FM breed, we applied a three-step approach, which combined admixture, genetic contribution, and FROH of individuals into a high-resolution network visualization. Based on this approach, we were able to demonstrate that population substructures, as detected by model-based clustering, can be either associated with a different genetic origin or with the progeny of most influential sires. Within the FM breed, admixed horses explained most of the genetic variance of the current breeding population, while OF horses only accounted for a small proportion of the variance. Furthermore, we illustrated that FM horses showed high TB admixture levels and we identified inconsistencies in the origin of FM horses descending from the Arabian stallion Doktryner. With the exception of WB, FM horses were less inbred compared to the other breeds. However, the relatively few but long ROH segments suggested diversity loss in both FM subpopulations. Genes located in FM- and OF-specific ROH islands had known functions involved in conformation and behaviour, two traits that are highly valued by breeders. CONCLUSIONS The FM remains the last native Swiss breed, clearly distinguishable from other historically introgressed breeds, but it suffered bottlenecks due to intensive selection of stallions, restrictive mating choices based on arbitrary definitions of pure breeding, and selection of rare coat colours. To preserve the genetic diversity of FM horses, future conservation managements strategies should involve a well-balanced selection of stallions (e.g., by integrating OF stallions in the FM breeding population) and avoid selection for rare coat colours

Pólipos da vesícula biliar. Como e quando tratar?

OBJETIVO: O objetivo do estudo é saber qual a orientação terapêutica para os doentes com pólipos vesiculares (PVs), que tipo de vigilância realizar, saber diferenciar entre um pólipo benigno e um pólipo maligno e proporcionar uma tranquilização em relação à "cancrofobia". Tipo de estudo: Realizou-se um estudo retrospectivo de cinco anos. Local: O estudo foi realizado nos Hospitais da Universidade de Coimbra, num Serviço de Cirurgia. População: Foram estudados todos os doentes operados no Serviço de Cirurgia II com o diagnóstico pré-operatório de PV, entre janeiro de 2003 e dezembro 2007. MÉTODOS: Foi feita correlação clínico-patológica de todos os doentes. Feita avaliação: de dados demográficos, da apresentação clínica, dos principais sintomas, das patologias associadas e exames complementares de diagnóstico realizados. RESULTADOS: Foram estudados 93 doentes, sendo que em 91 doentes tratava-se de pólipos benignos e em dois doentes de pólipos malignos. Dos 91 pólipos benignos, 73 (78,5%) eram pólipos de colesterol, 14 (15%) hiperplasias e dois (2,2%) adenomas. Em dois (2,2%) doentes tratava-se de pólipos malignos, adenocarcinoma da vesícula biliar. O diâmetro médio dos pólipos benignos é de 6 mm, 40 (43%) doentes apresentavam lesões múltiplas. Nos pólipos malignos e pré-malignos (adenomas) o diâmetro médio é de 18,8 mm, são todas lesões solitárias e a idade média destes doentes é de 57,7 anos. CONCLUSÃO: Conclui-se que o tratamento cirúrgico dos PVs é a colecistectomia e só deve ser realizado quando existe: clínica relacionada com o PV; pólipos de diâmetro superior a 10 mm; crescimento do pólipo num curto espaço de tempo; pólipo séssil ou base de inserção larga; pólipo com longo pedículo; idade do doente superior a 50 anos; coexistência de litíase vesicular; pólipos localizados no infundíbulo da vesícula ou alterações ecográficas na parede vesicular.OBJECTIVE: Appropriate treatment and timing hinge on whether the lesion is benign or malignant. Study: A five years retrospective descriptive analysis was performed. Location : Department of General Surgery in Hospitals of the University of Coimbra. Patients: We present a series of 93 consecutive patients who had elective surgery for known gallbladder polyps, treated from January 2003 to December 2007. METHODS: An analysis was performed using clinical and radiological files of patients electively treated for gallbladder polyp. Ninety-three consecutive patients were evaluated, treated and followed in a Department of General Surgery in a Central Hospital in that period. Biographic, clinical and radiological data were compiled. RESULTS: In 91 patients a benign lesion was found. Two (2.16%) patients had adenocarcinoma. Among benign polyps, 73 (78,5%) were cholesterol polyps, 14 (15%) were hyper-plastic and 2 (2.19%) were premalignant adenomas. Mean diameter of benign polyps, excluding adenomas, was 6 mm. In 40 (43%) patients, multiple lesions were found. The mean diameter in the subset of malignant and premalignant polyps was 18.8 mm, in all instances these were found to be single lesions; and mean age at presentation was 57,7 years. CONCLUSION: Cholecystectomy is the appropriate surgical treatment for gallbladder polyps, when removal is warranted. Patients benefitting from surgery are those who are symptomatic, whose polyps exceed 10 mm in diameter and , have shown to be enlarging, to be sessile or broad-based, to have long pedicles;and also have . infundibular polyps, coexisting gallstones or changes on the gallbladder wall appearance at ultrasonography

Headache during airplane travel (“airplane headache”): first case in Greece

Headache related to airplane flights is rare. We describe a 37-year-old female patient with multiple intense, jabbing headache episodes over the last 3 years that occur exclusively during airplane flights. The pain manifests during take-off and landing, and is located always in the left retro-orbital and frontotemporal area. It is occasionally accompanied by dizziness, but no additional symptoms occur. Pain intensity diminishes and disappears after 15–20 min. Apart from occasional dizziness, no other symptoms occur. The patient has a history of tension-type headache and polycystic ovaries. Blood tests and imaging revealed no abnormalities. Here, we present the first case in Greece. We review the current literature on this rare syndrome and discuss on possible pathophysiology and the investigation of possible co-factors such as anxiety and depression

The development of new biomarkers of spermatozoa quality in cattle

There is a current need for new biomarkers of spermatozoa quality, that consistently and correctly identify spermatozoa that will successfully contribute to subsequent embryo development. This could improve the standardization of semen analysis, decrease early embryo mortality, and use these biomarkers as a selection tool before servicing females. This study utilized imaging techniques to identify potential biomarkers of sperm quality, using sires previously classified as high (n = 4) or low (n = 4) performing at producing blastocysts in vitro. Spermatozoa were assessed before and following a gradient purification protocol, to understand how populations of cells are impacted by such protocols and may differ between in vivo and in vitro use. Pre-gradient samples from low-performing sires had an increased incidence of DNA damage, although post-gradient samples from high-performing sires were found to have an increased incidence of DNA damage. When evaluating morphology via fluorescent microscopy, the most prevalent defects in pre-gradient samples from high-performing sires were tail defects, which are successfully removed during purification processing. The most prevalent defects in pre-gradient samples from low-performing sires were aggresome defects located in the head, which would be brought into an oocyte upon fertilization and may impair embryo development. Image-based flow cytometry (IBFC) was employed to quantify defect prevalence to evaluate a greater sample size decreasing the variability that exists in manual assessments. Using IBFC, aggresome defects were again identified in the heads of spermatozoa from low-performing sires. Post-gradient samples from low-performing sires had a significantly greater (p < 0.05) incidence of aggresome defects than post-gradient samples from high-performing sires. Additionally, IBFC was used to evaluate spermatozoa viability following gradient purification. Distinct populations of sperm cells were identified. High-performing sires had more spermatozoa in the population deemed most viable than low-performing sires. This study demonstrated that spermatozoa defects vary in populations before and following gradient purification, indicating that it may be beneficial to separately evaluate semen for in vivo and in vitro use. Furthermore, a prevalent defect in low-performing sires that could explain a discrepancy between successful fertilization and embryo development was identified. Therefore, elucidating a malfunction regulated by sire, that could potentially affect early embryo development

Physical activity: a strategy to improve antibody response to a SARS-CoV-2 vaccine booster dose in patients with autoimmune rheumatic diseases.

Physical activity associates with improved immunogenicity following a 2-dose schedule of CoronaVac (Sinovac's inactivated SARS-CoV-2 vaccine) in patients with autoimmune rheumatic diseases (ARD). This study evaluates whether physical activity impacts vaccine-induced antibody responses to a booster dose in this population. This was a phase-4 trial conducted in Sao Paulo, Brazil. Patients with ARD underwent a 3-dose schedule of CoronaVac. One month after the booster, we assessed seroconversion rates of anti-SARS-CoV-2 S1/S2 IgG, geometric mean titers of anti-S1/S2 IgG, frequency of positive neutralizing antibodies, and neutralizing activity. Physical activity was assessed through questionnaire. Physically active (n = 362) and inactive (n = 278) patients were comparable for most characteristics; however, physically active patients were younger (P<.01) and had a lower frequency of chronic inflammatory arthritis (P<.01). Adjusted models showed that physically active patients had -2 times odds of seroconversion rates (OR: 2.09; 95% confidence interval, 1.22 to 3.61), -22% greater geometric mean titers of anti-S1/S2 IgG (22.09%; 95% confidence interval, 3.91 to 65.60), and -7% greater neutralizing activity (6.76%; 95% confidence interval, 2.80 to 10.72) than inactive patients. Patients with ARD who are physically active have greater odds of experiencing better immunogenicity to a booster dose of CoronaVac. These results support the recommendation of physical activity to improve vaccination responses, particularly for immunocompromised individuals

No associations between physical activity and immunogenicity in SARS-CoV-2 seropositive patients with autoimmune rheumatic diseases prior to and after vaccination.

To investigate the association between physical activity and immunogenicity among SARS-CoV-2 seropositive patients with autoimmune rheumatic diseases prior to and following a 2-dose schedule of CoronaVac (Sinovac inactivated vaccine). This was a prospective cohort study within an open-label, single-arm, phase 4 vaccination trial conducted in Sao Paulo, Brazil. In this substudy, only SARS-CoV-2 seropositive patients were included. Immunogenicity was assessed by seroconversion rates of total anti-SARS-CoV-2 S1/S2 immunoglobulin G (IgG), geometric mean titers of anti-S1/S2 IgG, frequency of positive neutralizing antibodies, and neutralizing activity before and after vaccination. Physical activity was assessed through a questionnaire. Model-based analyses were performed controlling for age (30 kg/m2), and use of prednisone, immunosuppressants, and biologics. A total of 180 seropositive autoimmune rheumatic disease patients were included. There was no association between physical activity and immunogenicity before and after vaccination. This study suggests that the positive association between physical activity and greater antibody responses seen in immunocompromised individuals following vaccination is overridden by previous SARS-CoV-2 infection, and does not extend to natural immunity

Tucatinib, Trastuzumab, and Capecitabine for HER2-Positive Metastatic Breast Cancer

BACKGROUND: Patients with human epidermal growth factor receptor 2 (HER2)-positive metastatic breast cancer who have disease progression after therapy with multiple HER2-targeted agents have limited treatment options. Tucatinib is an investigational, oral, highly selective inhibitor of the HER2 tyrosine kinase. METHODS: We randomly assigned patients with HER2-positive metastatic breast cancer previously treated with trastuzumab, pertuzumab, and trastuzumab emtansine, who had or did not have brain metastases, to receive either tucatinib or placebo, in combination with trastuzumab and capecitabine. The primary end point was progression-free survival among the first 480 patients who underwent randomization. Secondary end points, assessed in the total population (612 patients), included overall survival, progression-free survival among patients with brain metastases, confirmed objective response rate, and safety. RESULTS: Progression-free survival at 1 year was 33.1% in the tucatinib-combination group and 12.3% in the placebo-combination group (hazard ratio for disease progression or death, 0.54; 95% confidence interval [CI], 0.42 to 0.71; P<0.001), and the median duration of progression-free survival was 7.8 months and 5.6 months, respectively. Overall survival at 2 years was 44.9% in the tucatinib-combination group and 26.6% in the placebo-combination group (hazard ratio for death, 0.66; 95% CI, 0.50 to 0.88; P = 0.005), and the median overall survival was 21.9 months and 17.4 months, respectively. Among the patients with brain metastases, progression-free survival at 1 year was 24.9% in the tucatinib-combination group and 0% in the placebo-combination group (hazard ratio, 0.48; 95% CI, 0.34 to 0.69; P<0.001), and the median progression-free survival was 7.6 months and 5.4 months, respectively. Common adverse events in the tucatinib group included diarrhea, palmar-plantar erythrodysesthesia syndrome, nausea, fatigue, and vomiting. Diarrhea and elevated aminotransferase levels of grade 3 or higher were more common in the tucatinib-combination group than in the placebo-combination group. CONCLUSIONS: In heavily pretreated patients with HER2-positive metastatic breast cancer, including those with brain metastases, adding tucatinib to trastuzumab and capecitabine resulted in better progression-free survival and overall survival outcomes than adding placebo; the risks of diarrhea and elevated aminotransferase levels were higher with tucatinib. (Funded by Seattle Genetics; HER2CLIMB ClinicalTrials.gov number, NCT02614794.)

WHO Global Survey on Maternal and Perinatal Health in Latin America: classifying caesarean sections

<p>Abstract</p> <p>Background</p> <p>Caesarean section rates continue to increase worldwide with uncertain medical consequences. Auditing and analysing caesarean section rates and other perinatal outcomes in a reliable and continuous manner is critical for understanding reasons caesarean section changes over time.</p> <p>Methods</p> <p>We analyzed data on 97,095 women delivering in 120 facilities in 8 countries, collected as part of the 2004-2005 Global Survey on Maternal and Perinatal Health in Latin America. The objective of this analysis was to test if the "10-group" or "Robson" classification could help identify which groups of women are contributing most to the high caesarean section rates in Latin America, and if it could provide information useful for health care providers in monitoring and planning effective actions to reduce these rates.</p> <p>Results</p> <p>The overall rate of caesarean section was 35.4%. Women with single cephalic pregnancy at term without previous caesarean section who entered into labour spontaneously (groups 1 and 3) represented 60% of the total obstetric population. Although women with a term singleton cephalic pregnancy with a previous caesarean section (group 5) represented only 11.4% of the obstetric population, this group was the largest contributor to the overall caesarean section rate (26.7% of all the caesarean sections). The second and third largest contributors to the overall caesarean section rate were nulliparous women with single cephalic pregnancy at term either in spontaneous labour (group 1) or induced or delivered by caesarean section before labour (group 2), which were responsible for 18.3% and 15.3% of all caesarean deliveries, respectively.</p> <p>Conclusion</p> <p>The 10-group classification could be easily applied to a multicountry dataset without problems of inconsistencies or misclassification. Specific groups of women were clearly identified as the main contributors to the overall caesarean section rate. This classification could help health care providers to plan practical and effective actions targeting specific groups of women to improve maternal and perinatal care.</p

Diversity and Relatedness Enhance Survival in Colour Polymorphic Grasshoppers

Evolutionary theory predicts that different resource utilization and behaviour by alternative phenotypes may reduce competition and enhance productivity and individual performance in polymorphic, as compared with monomorphic, groups of individuals. However, firm evidence that members of more heterogeneous groups benefit from enhanced survival has been scarce or lacking. Furthermore, benefits associated with phenotypic diversity may be counterbalanced by costs mediated by reduced relatedness, since closely related individuals typically are more similar. Pygmy grasshoppers (Tetrix subulata) are characterized by extensive polymorphism in colour pattern, morphology, behaviour and physiology. We studied experimental groups founded by different numbers of mothers and found that survival was higher in low than in high density, that survival peaked at intermediate colour morph diversity in high density, and that survival was independent of diversity in low density where competition was less intense. We further demonstrate that survival was enhanced by relatedness, as expected if antagonistic and competitive interactions are discriminately directed towards non-siblings. We therefore also performed behavioural observations and staged encounters which confirmed that individuals recognized and responded differently to siblings than to non-siblings. We conclude that negative effects associated with competition are less manifest in diverse groups, that there is conflicting selection for and against genetic diversity occurring simultaneously, and that diversity and relatedness may facilitate the productivity and ecological success of groups of interacting individuals