Genetic Analysis of White Facial and Leg Markings in the Swiss Franches-Montagnes Horse Breed

White markings and spotting patterns in animal species are thought to be a result of the domestication process. They often serve for the identification of individuals but sometimes are accompanied by complex pathological syndromes. In the Swiss Franches-Montagnes horse population, white markings increased vastly in size and occurrence during the past 30 years, although the breeding goal demands a horse with as little depigmented areas as possible. In order to improve selection and avoid more excessive depigmentation on the population level, we estimated population parameters and breeding values for white head and anterior and posterior leg markings. Heritabilities and genetic correlations for the traits were high (h2 > 0.5). A strong positive correlation was found between the chestnut allele at the melanocortin-1-receptor gene locus and the extent of white markings. Segregation analysis revealed that our data fit best to a model including a polygenic effect and a biallelic locus with a dominant-recessive mode of inheritance. The recessive allele was found to be the white trait-increasing allele. Multilocus linkage disequilibrium analysis allowed the mapping of the putative major locus to a chromosomal region on ECA3q harboring the KIT gen

Sintomas depressivos e distúrbios motores axiais em indivíduos com doença de Parkinson : um estudo transversal

Background: Depression is an important nonmotor symptom of Parkinson's disease (PD) and has been associated with the motor symptoms in these individuals. Objectives: To determine whether there are relationships between depressive symptoms and abnormalities in axial postural alignment and axial motor deficits, especially postural instability, and trunk rigidity in PD. Methods: In this cross-sectional study, 65 individuals were evaluated using the Beck Depression Inventory-II (BDI-II) for the analysis of depressive symptoms and underwent a postural assessment of head, trunk, and hip sagittal alignment through computerized photogrammetry. The MDS-UPDRS was used to assess clinical aspects of PD, the Trunk Mobility Scale was used to assess axial rigidity, and the MiniBESTest to assess balance. To determine the relationship between depressive symptoms and postural alignment, multiple linear regression analysis was performed. Results: The participants with depressive symptoms had more severe motor deficits as well as greater trunk rigidity and worse postural instability (p < 0.05). When the postural angles were compared between men and women using Student's t-test, it was found that men had greater flexion angles of the head (p = 0.003) and trunk (p = 0.017). Using multiple linear regression analysis corrected for the age and sex of the participants, we verified that the anterior trunk inclination was significantly larger in the PD population with depressive symptoms (R2 = 0.453, β = 0.116, and p = 0.045). Conclusion: PD individuals with depressive symptoms have more severe flexed trunk posture, mainly in older men. Additionally, more severe depressive symptoms are associated with worsening postural instability, trunk rigidity and motor deficits in this population.Antecedentes: A depressão é um sintoma não motor importante da doença de Parkinson (DP) e tem sido associada aos sintomas motores nesses indivíduos. Objetivos: Determinar se existem relações entre sintomas depressivos e anormalidades no alinhamento postural axial e déficits motores axiais, especialmente instabilidade postural e rigidez de tronco na DP. Métodos: Neste estudo transversal, 65 indivíduos foram avaliados pelo BDI-II para análise de sintomas depressivos e submetidos à avaliação postural do alinhamento sagital de cabeça, tronco e quadril por meio de fotogrametria computadorizada. A MDS-UPDRS avaliou os aspectos clínicos, TMS avaliou rigidez axial e o MiniBESTest equilíbrio. Para determinar a relação entre sintomas depressivos e alinhamento postural, realizou-se uma análise de regressão linear múltipla. Resultados: Os participantes com sintomas depressivos apresentaram déficits motores mais graves, bem como maior rigidez de tronco e pior instabilidade postural (p < 0,05). Quando comparados os ângulos posturais entre homens e mulheres pelo teste t de Student, verificou-se que os homens apresentaram maiores graus de flexão da cabeça (p = 0,003) e do tronco (p = 0,017). Por meio da análise de regressão linear múltipla corrigida para a idade e sexo dos participantes, verificamos que a inclinação anterior do tronco foi significativamente maior nos indivíduos com DP com sintomas depressivos do que sem sintomas depressivos (R2 = 0,453, β = 0,116 e p = 0,045) Conclusão: Indivíduos com DP com sintomas depressivos apresentam postura de tronco flexionado mais severa, principalmente em homens mais idosos. Além disso, os sintomas depressivos mais graves pioram significativamente a instabilidade postural, a rigidez do tronco e os déficits motores nessa população

Prevalence and incidence of Parkinson's disease and other forms of parkinsonism in a cohort of elderly individuals in Southern Brazil : protocol for a population-based study

Introduction Parkinsonism is one of the most common neurological disorders affecting the elderly. Several population-based studies have determined the epidemiology of parkinsonism, mainly Parkinson’s disease (PD), but there is still little evidence in the Brazilian population. This protocol study aims to assess the prevalence and incidence of cases of PD and other parkinsonian syndromes in a 5-year cohort in a population-based study in the southern region of Brazil. Methods and analysis A prospective population-based longitudinal study, with a cohort of development of cases of parkinsonism, divided into two phases: in phase I, two questionnaires to screen for parkinsonism (Tanner’s questionnaire), Rapid Eyes Movement (REM) sleep behaviour disorder (REM Sleep Behavior Disorder Single-Question Screen) and a short interview will be conducted with all elderly residents of Veranópolis (the first longevity Brazilian county located in the Rio Grande do Sul, Brazil) aged 60 or over. The positive screened cases will be examined independently by at least two movement disorder-trained physicians and prevalence will be determined. A comprehensive evaluation of prodromic symptoms, risk factors and clinical characteristics will be carried out. Subjects with subtle parkinsonism and a sample of healthy subjects will be followed for 5 years in a developmental cohort of parkinsonism cases. For crude incidence, all individuals admitted at the beginning of the study will be re-evaluated

Accumulating mutations in series of haplotypes at the KIT and MITF loci are major determinants of white markings in Franches-Montagnes horses.

Coat color and pattern variations in domestic animals are frequently inherited as simple monogenic traits, but a number are known to have a complex genetic basis. While the analysis of complex trait data remains a challenge in all species, we can use the reduced haplotypic diversity in domestic animal populations to gain insight into the genomic interactions underlying complex phenotypes. White face and leg markings are examples of complex traits in horses where little is known of the underlying genetics. In this study, Franches-Montagnes (FM) horses were scored for the occurrence of white facial and leg markings using a standardized scoring system. A genome-wide association study (GWAS) was performed for several white patterning traits in 1,077 FM horses. Seven quantitative trait loci (QTL) affecting the white marking score with p-values p≤10(-4) were identified. Three loci, MC1R and the known white spotting genes, KIT and MITF, were identified as the major loci underlying the extent of white patterning in this breed. Together, the seven loci explain 54% of the genetic variance in total white marking score, while MITF and KIT alone account for 26%. Although MITF and KIT are the major loci controlling white patterning, their influence varies according to the basic coat color of the horse and the specific body location of the white patterning. Fine mapping across the MITF and KIT loci was used to characterize haplotypes present. Phylogenetic relationships among haplotypes were calculated to assess their selective and evolutionary influences on the extent of white patterning. This novel approach shows that KIT and MITF act in an additive manner and that accumulating mutations at these loci progressively increase the extent of white markings

Rationale, study design, and analysis plan of the Alveolar Recruitment for ARDS Trial (ART): Study protocol for a randomized controlled trial

Background: Acute respiratory distress syndrome (ARDS) is associated with high in-hospital mortality. Alveolar recruitment followed by ventilation at optimal titrated PEEP may reduce ventilator-induced lung injury and improve oxygenation in patients with ARDS, but the effects on mortality and other clinical outcomes remain unknown. This article reports the rationale, study design, and analysis plan of the Alveolar Recruitment for ARDS Trial (ART). Methods/Design: ART is a pragmatic, multicenter, randomized (concealed), controlled trial, which aims to determine if maximum stepwise alveolar recruitment associated with PEEP titration is able to increase 28-day survival in patients with ARDS compared to conventional treatment (ARDSNet strategy). We will enroll adult patients with ARDS of less than 72 h duration. The intervention group will receive an alveolar recruitment maneuver, with stepwise increases of PEEP achieving 45 cmH(2)O and peak pressure of 60 cmH2O, followed by ventilation with optimal PEEP titrated according to the static compliance of the respiratory system. In the control group, mechanical ventilation will follow a conventional protocol (ARDSNet). In both groups, we will use controlled volume mode with low tidal volumes (4 to 6 mL/kg of predicted body weight) and targeting plateau pressure &lt;= 30 cmH2O. The primary outcome is 28-day survival, and the secondary outcomes are: length of ICU stay; length of hospital stay; pneumothorax requiring chest tube during first 7 days; barotrauma during first 7 days; mechanical ventilation-free days from days 1 to 28; ICU, in-hospital, and 6-month survival. ART is an event-guided trial planned to last until 520 events (deaths within 28 days) are observed. These events allow detection of a hazard ratio of 0.75, with 90% power and two-tailed type I error of 5%. All analysis will follow the intention-to-treat principle. Discussion: If the ART strategy with maximum recruitment and PEEP titration improves 28-day survival, this will represent a notable advance to the care of ARDS patients. Conversely, if the ART strategy is similar or inferior to the current evidence-based strategy (ARDSNet), this should also change current practice as many institutions routinely employ recruitment maneuvers and set PEEP levels according to some titration method.Hospital do Coracao (HCor) as part of the Program 'Hospitais de Excelencia a Servico do SUS (PROADI-SUS)'Brazilian Ministry of Healt

Genetic analysis of white facial and leg markings in the Swiss Franches-Montagnes Horse Breed

White markings and spotting patterns in animal species are thought to be a result of the domestication process. They often serve for the identification of individuals but sometimes are accompanied by complex pathological syndromes. In the Swiss Franches-Montagnes horse population, white markings increased vastly in size and occurrence during the past 30 years, although the breeding goal demands a horse with as little depigmented areas as possible. In order to improve selection and avoid more excessive depigmentation on the population level, we estimated population parameters and breeding values for white head and anterior and posterior leg markings. Heritabilities and genetic correlations for the traits were high (h(2) > 0.5). A strong positive correlation was found between the chestnut allele at the melanocortin-1-receptor gene locus and the extent of white markings. Segregation analysis revealed that our data fit best to a model including a polygenic effect and a biallelic locus with a dominant-recessive mode of inheritance. The recessive allele was found to be the white trait-increasing allele. Multilocus linkage disequilibrium analysis allowed the mapping of the putative major locus to a chromosomal region on ECA3q harboring the KIT gene