[BLIRD - a new genetic disease in Holstein cattle in Switzerland]. / BLIRD ­ eine neue genetische Erkrankung beim Holsteinrind in der Schweiz.

INTRODUCTION: Recently, a new hereditary disease, bovine lymphocyte intestinal retention defect (BLIRD), was discovered in Holstein cattle in France and is caused by a variant in the Integrin subunit beta 7 (ITGB7) gene. The altered cell adhesion molecule resulting from this point mutation is responsible for an impaired tissue of CD4 T lymphocytes from the blood to intestinal tissue. The aim of this study was to assess the allelic frequency of this deleterious variant in the local Holstein population and to clinically examine ten BLIRD-affected Holstein cattle from Switzerland in order to characterise the phenotype of this new hereditary disease, which is still unknown to the veterinary community. BLIRD was associated with severely impaired animal health in the rearing phase and significantly reduced animal welfare due to weakened immune defences, below-average development and recurrent diarrhoea. Further examinations revealed increased leucocyte values and a slightly increased average age at first calving. Affected homozygous animals are labelled internationally as BLIRD-carrier homozygous (LRS), BLIRD-carrier heterozygous (LRC) and BLIRD-free (LRF). An obvious inbreeding practice was clearly demonstrated by the pedigree analysis of the ten animals, which all trace back to the potential founder bull. Herein, BLIRD has been detected and described in Switzerland for the first time. The ITGB7 variant allele has a frequency of 2,1 % in the current Swiss Holstein population, which is below the level of the cholesterol deficiency (CD)-associated apolipoprotein B (APOB) variant allele with a frequency of 3,9 %. Although relatively rare, attention should be paid to the BLIRD genotype when mating in order to exclude further affected animals. In cattle with clinically suspected BLIRD, the diagnosis should be confirmed by genetic testing.

INTRODUCTION: Récemment, une nouvelle maladie héréditaire récessive, le défaut de rétention intestinale des lymphocytes bovins (bovine lymphocyte intestinal retention defect BLIRD), a été découverte chez les bovins Holstein en France. Elle est causée par une variante du gène Integrin subunit beta 7 (ITGB7). L'altération de la molécule d'adhésion cellulaire résultant de cette mutation ponctuelle est responsable de l'altération du transfert des lymphocytes T CD4 du sang vers le tissu intestinal. L'objectif de cette étude était d'évaluer la fréquence allélique de cette variante délétère dans la population Holstein locale et d'examiner cliniquement dix bovins Holstein suisses atteints de BLIRD afin de caractériser le phénotype de cette nouvelle maladie héréditaire, qui est encore inconnue de la communauté vétérinaire. La BLIRD a été associée à une grave détérioration de la santé des animaux pendant la phase d'élevage et à une réduction significative de leur bien-être en raison de l'affaiblissement des défenses immunitaires, d'un développement inférieur à la moyenne et de diarrhées récurrentes. Des examens complémentaires ont révélé une augmentation des valeurs leucocytaires et une légère augmentation de l'âge moyen au premier vêlage. Les animaux homozygotes affectés sont étiquetés au niveau international comme homozygotes porteurs de BLIRD (LRS), hétérozygotes porteurs de BLIRD (LRC) et exempts de BLIRD (LRF). Une pratique de consanguinité évidente a été clairement démontrée par l'analyse généalogique des dix animaux, qui remontent tous au taureau fondateur potentiel. La BLIRD a été ainsi détectée et décrite pour la première fois en Suisse. La allèle délétère ITGB7 a une fréquence de 2,1 % dans la population Holstein suisse actuelle, ce qui est inférieur au niveau de la allèle délétère de l'apolipoprotéine B (APOB) associée à la déficience en cholestérol (CD), dont la fréquence est de 3,9 %. Bien que relativement rare, il convient de prêter attention au génotype BLIRD lors de l'accouplement afin d'exclure de la reproduction d'autres animaux affectés.

Ecological risk of metals in Andean water resources: A framework for early environmental assessment of mining projects in Peru.

Metallic contaminants in Andean water resources influenced by mining activities poses risks to aquatic ecosystems and a challenge to regulatory agencies responsible for environmental compliance. In this study, the Ecological Risk Assessment (ERA) framework was adapted to assess dissolved heavy metal concentrations at 283 surface water monitoring stations near to six mining projects during the dry and wet seasons. Reports from OEFA-Peru on Early Environmental Assessment (EEA) were used to apply various criteria and non-parametric statistical tests. They included ecological, ecotoxicological, chemical, and regulatory factors. The main goal of this research was to identify, analyze, characterize, and compare the risks present at different trophic levels. These levels were categorized as T1 (Microalgae), T2 (Zooplankton and Benthic invertebrates), and T3 (Fish). Individual risk (IR) was estimated using the quotient model, while total risk (TR) was assessed using the additive probability rule. Rainbow trout (Oncorhynchus mykiss), representing trophic level T3, showed the highest sensitivity to Fe and Cu. Statistical tests ranked the IR as Fe > Cu > Zn > Mn > Pb (p < 0.01). The TR was more prevalent during the wet season compared to the dry season (p < 0.01). Notably, around 50 % of the monitoring stations (n = 142) were classified as high risk, and 9 % (n = 13) showed extremely high-risk values for Cu and Fe. The adapted ERA framework demonstrated great effectiveness in identifying critical points of metal contamination in high Andean aquatic ecosystems under mining influence. However, specialized studies are suggested that allow the sources of pollution to be associated with specific regulatory actions.

Multiple independent de novo mutations are associated with the development of schistosoma reflexum, a lethal syndrome in cattle.

Schistosoma reflexum (SR) is a lethal congenital syndrome characterized by U-shaped dorsal retroflexion of the spine and exposure of abdominal viscera. SR is usually associated with severe dystocia. The syndrome is thought to be inherited as a Mendelian trait. We collected a series of 23 SR-affected calves from four breeds (20 Holstein, one Red Danish, one Limousin, one Romagnola) and performed whole-genome sequencing (WGS). WGS was performed on 51 cattle, including 14 cases with parents (trio-based; Group 1) and nine single cases (solo-based; Group 2). Sequencing-based genome-wide association studies with 20 Holstein cases and 154 controls showed no association (above Bonferroni threshold; P-value<3 ×10-09). Assuming a monogenic recessive inheritance, no region of shared homozygosity was observed, suggesting heterogeneity. Alternatively, the presence of possible dominant acting de novo mutations were assessed. In Group 1, heterozygous private variants, absent in both parents, were found in seven cases. These involved the ACTL6A, FLNA, GLG1, IQSEC2, MAST3, MBTPS2, and MLLT1 genes. In addition, heterozygous private variants affecting the genes DYNC1LI1, PPP2R2B, SCAF8, SUGP1, and UBP1 were identified in five cases from Group 2. The detected frameshift and missense variants are predicted to cause haploinsufficiency. Each of these 12 affected genes belong to the class of haploinsufficient loss-of-function genes or are involved in embryonic and pre-weaning lethality or are known to be associated with severe malformation syndromes in humans and/or mice. This study presents for the first time a detailed genomic evaluation of bovine SR, suggesting that independent de novo mutations may explain the sporadic occurrence of SR in cattle.

Health and welfare assessment of beef cattle during the adaptation period in a specialized commercial fattening unit.

Beef cattle welfare and health status are influenced by housing and management systems. The present study aimed to assess the welfare and health status in the first 15 days after arrival of Limousine bulls imported from France and fattened in a commercial fattening unit in Italy. A total of 264 bulls were included in the study. Welfare, biosecurity, and major hazard and warning system were assessed on days 2 (T1) and 15 (T2) after arrival to the unit. At T1 and T2 an inspective clinical examination was performed on all bulls. At T1 and T2 blood samples were collected from 88 bulls for haematological analysis. Both at T1 and T2, the welfare, biosecurity, and major hazards and warning systems were classified with a general score of medium but with a decrease on animal-based measurements in T2. At T1 and T2 the clinical examination revealed a significant increase (p-value≤0.05) of skin lesions and lameness in T2. A high incidence of respiratory disease was noticed in both assessed times. Leucocytes and all differentials count, and platelets were significantly increased (p-value≤0.05) at T2, while the fibrinogen was significantly decreased. The haematological changes suggest that the bulls were under higher stress in T2 when compared with T1 linked with a difficult adaptation response to the fattening unit. A multi-factorial approach that integrates the indicators of the checklist and the clinical and haematological findings of animals can be a useful method to deepen the assessment of welfare in beef cattle.

Infrared Thermography, Intratendon Vascular Resistance, and Echotexture in Athletes with Patellar Tendinopathy: A Cross-Sectional Study.

Ultrasonographic signs of tendinopathies are an increase in thickness, loss of alignment in collagen fibers and the presence of neovascularization. Nevertheless, analysis of intratendinous vascular resistance (IVR) can be more useful for understanding the physiological state of the tissue. To show thermal, echotextural, and Doppler signal differences in athletes with patellar tendinopathy and controls. Twenty-six athletes with patellar tendinopathy (PT) participants (30.1 years; SD = 9.0 years) and 27 asymptomatic athletes (23.3 years; SD = 5.38 years) were evaluated with thermographic and Doppler ultrasonography (DS). Area of Doppler signals (DS), echotextural parameters (echointensity and echovariation) and IVR were determined by image analysis. The statistical analysis was performed by Bayesian methods and the results were showed by Bayes Factor (BF10: probability of alternative hypothesis over null hypothesis), and Credibility intervals (CrI) of the effect. The absolute differences of temperature (TD) were clearly greater (BF10 = 19) in the tendinopathy group (patients) than in controls. Regarding temperature differences between the affected and healthy limb, strong evidence was found (BF10 = 14) for a higher temperature (effect = 0.53°C; 95% CrI = 0.15°C-0.95°C) and very strong for reduced IVR compared (BF10 = 71) (effect = -0.67; 95% CrI = -1.10 to 0.25). The differences in area of DS (BF10 = 266) and EV (BF10 = 266) were higher in tendinopathy group. TD showed a moderate positive correlation with VISA-P scores (tau-B = .29; 95% CrI = .04-.51) and strong correlation with IVR (r = -.553; 95%CrI = -.75 to .18). Athletes with patellar tendinopathy showed a more pronounced thermal difference, a larger area of Doppler signal, a lower IVR and a moderately higher echovariaton than controls. The correlation between temperature changes and IVR might be related with the coexistence of degenerative and inflammatory process in PT.

Short communication: Prevalence of deleterious variants causing recessive disorders in Italian Chianina, Marchigiana and Romagnola cattle.

In the last two decades, the molecular cause of six monogenic autosomal recessive disorders has been identified in native Italian beef cattle: two different ATP2A1 variants for the pseudomyotonia congenita, the first in Chianina and Romagnola (PMT1) and the second in Romagnola (PMT2); a KDM2B variant for the paunch calf syndrome (PCS) in Marchigiana and Romagnola; a NID1 variant for the congenital cataract (CC) in Romagnola; a LAMB1 variant for the hemifacial microsomia (HFM) in Romagnola; an ABCA12 variant for the ichthyosis fetalis (IF) in Chianina and a FA2H variant for the ichthyosis congenita (IC) in Chianina. The aim of this study was to evaluate the potential impact of these disorders in the affected Italian populations. For this purpose, 3331 Chianina, 2812 Marchigiana and 1680 Romagnola bulls born in the last 40 years were considered. The allelic frequency (AF) of the variant for PMT1 was 1.0% in Romagnola, 4.6% in Marchigiana and 5.9% in Chianina. The AF of the variant for PMT2 was 3.3% in Romagnola and 0% in the other two breeds. The AF of the variant for PCS was 11.7% in Romagnola, 2.0% in Marchigiana and 0% in Chianina. The AF of the variants for CC, HFM, IF and IC resulted below 3%, being the variants detected only in the breed populations in which they were previously reported. Considering a selected male population in the single breed, Chianina showed carrier prevalence of 11.9% for PMT1, 7.7% for IC and 6.4% for IF. Romagnola showed carrier prevalence of 23.4% for PCS, 6.7% for PMT2, 4.1% for HFM, 3.2% for CC and 2.0% for PMT1. Marchigiana showed carrier prevalence of 9.1% for PMT1 and 4.0% for PCS. With respect to the Romagnola cattle, the concerning presence of a total of five defect alleles in the population hampers a general approach based on the prevention of carriers from artificial insemination. However, identification of carriers may allow conscious mating to prevent the risk of homozygous descendants as well as the spread of heterozygous offspring. Therefore, systematic genotyping for all seven known harmful alleles is recommended to prevent risk mating between carriers, in particular to avoid the occurrence of affected offspring.

Clinical presentation and outcome of human papillomavirus-positive nasopharyngeal carcinoma in a North American cohort.

BACKGROUND: The objective of this study was to describe the clinical presentation and outcomes of human papillomavirus (HPV)-positive nasopharyngeal cancer (NPC) versus Epstein-Barr virus (EBV)-positive NPC and HPV-positive oropharyngeal cancer (OPC). METHODS: Clinical characteristics and presenting signs/symptoms were compared between patients who had viral-related NPC versus viral-related OPC treated with intensity-modulated radiotherapy from 2005 to 2020 and who were matched 1:1 (by tumor and lymph node categories, smoking, age, sex, histology, and year of diagnosis). Locoregional control (LRC), distant control (DC), and overall survival (OS) were compared using the 2005-2018 cohort to maintain 2 years of minimum follow-up. Multivariable analysis was used to evaluate the cohort effect. RESULTS: Similar to HPV-positive OPC (n = 1531), HPV-positive NPC (n = 29) occurred mostly in White patients compared with EBV-positive NPC (n = 422; 86% vs. 15%; p < .001). Primary tumor volumes were larger in HPV-positive NPC versus EBV-positive NPC (median volume, 51 vs. 23 cm3 ; p = .002), with marginally more Level IB nodal involvement. More patients with HPV-positive NPC complained of local pain (38% vs. 3%; p = .002). The median follow-up for the 2005-2018 cohort was 5.3 years. Patients who had HPV-positive NPC (n = 20) had rates of 3-year LRC (95% vs. 90%; p = .360), DC (75% vs. 87%; p = .188), and OS (84% vs. 89%; p = .311) similar to the rates in those who had EBV-positive NPC (n = 374). Patients who had HPV-positive NPC also had rates of LRC (95% vs. 94%; p = .709) and OS (84% vs. 87%; p = .440) similar to the rates in those who had HPV-positive OPC (n = 1287). The DC rate was lower in patients who had HPV-positive disease (75% vs. 90%; p = .046), but the difference became nonsignificant (p = .220) when the analysis was adjusted for tumor and lymph node categories, smoking, and chemotherapy. CONCLUSIONS: HPV-positive NPC and EBV-positive NPC seem to be mutually exclusive diseases. Patients who have HPV-positive NPC have greater local symptom burden and larger primary tumors but have similar outcomes compared with patients who have EBV-positive NPC or HPV-positive OPC.

Reliability of a New Semi-automatic Image Analysis Method for Evaluating the Doppler Signal and Intratendinous Vascular Resistance in Patellar Tendinopathy.

The aim of this study was to determine the intra- and inter-rater reliability of a new semi-automatic image analysis method for quantification of the shape of the Doppler signal and the intratendinous vascular resistance in patellar tendinopathy. Thirty athletes (27.4 y, standard deviation = 8.57 y) with patellar intratendinous vascularity were included in a cross-sectional study (42 tendons analyzed). The intratendinous blood flow was assessed with power Doppler and ImageJ (Version 1.50b, National Institutes of Health, Bethesda, MD, USA) quantification software over a manually selected region of interest. Two blinded observers performed the analysis of the Doppler signal (vascular resistance) and shape descriptors (number of signals, pixel intensity, area, perimeter, major diameter, minor diameter, circularity and solidity). The intraclass correlation coefficient (ICC) was calculated, and the Bland-Altman mean of differences (MoD) and 95% limits of agreement (LoA) were determined. Also, small real differences (SRDs) and the standard error of measurement (SEM) were calculated. Intra-rater reliability was at a maximum for area (ICC = 0.999, 95% confidence interval [CI] = 0.998-0.999) and at a minimum for solidity (ICC = 0.782, 95% CI: 0.682-0.853). The MoD and 95% LoA were very low, and the relative SRD and SEM were below 5.3% and 2%, respectively. The inter-rater reliability was the maximum for area (ICC = 0.993, 95% CI = 0.989-0.996) and the minimum for circularity (ICC = 0.73; 95% CI=0.611-0.817). The MoD and 95% LoA were low, with the SRD and SEM below 6% and 2.2%. The proposed quantitative method for studying the intratendinous Doppler signal in the patellar tendon is reliable and reproducible.

Assessing the Effect of Radiotherapy in Addition to Surgery in Colon Adenocarcinomas: a Systematic Review and Meta-analysis of Contemporary Evidence.

PURPOSE: This study aims to review the contemporary evidence investigating radiotherapy (RT) in addition to surgery for colon adenocarcinomas. METHODS: We searched the following databases: PubMed, Science Direct, Scopus, ASCOpubs, the Cochrane Library, and Google Scholar. Studies (since January 2005) comparing outcomes of high-risk colon adenocarcinomas who underwent RT in addition to surgery versus no RT were eligible. Pooling of outcomes from published results or from analysis of survival curves was done. Subgroup analysis was conducted to determine if the efficacy of RT varies with RT timing. RESULTS: Eight studies were included (five retrospective cohorts, three population-based studies). Pooled analysis from retrospective cohorts showed a reduction in 5-year LR (OR 0.41; 95% CI 0.21-0.79; p = 0.007) in the RT group. A benefit in 3-year (OR 1.81; 95% CI 1.15-2.87; p = 0.01) and 5-year (OR 2.10; 95% CI 1.21-3.63; p = 0.008) DFS and in 3-year (OR 2.55; 95% CI 1.43-4.54; p = 0.001) and 5-year (OR 2.00; 95% CI 1.17-3.41; p = 0.01) OS was seen in the RT group. The OS benefit was demonstrated in the subgroup analysis of neoadjuvant RT, but not with adjuvant RT. The improvement in OS with neoadjuvant RT was supported by a population-based study from NCDB, while results from two population-based studies investigating adjuvant RT were conflicting. CONCLUSION: Taking into account the limitations of the studies, our review of evidence suggests a possible role of RT in improving oncologic outcomes of select colon adenocarcinomas. Prospective studies are needed to definitively assess the value of RT for colon cancer.

Reirradiation for Recurrent Nasopharyngeal Carcinomas: Experience From an Academic Tertiary Center in a Low- to Middle-Income Country.

PURPOSE: The objectives of this study were to report the oncologic outcomes and the treatment-related toxicities after reirradiation (re-RT) for recurrent nasopharyngeal carcinoma (rNPC) at our institution and to apply a recently published prognostic model for survival in rNPC in our cohort. PATIENTS AND METHODS: Thirty-two patients with rNPC treated at the authors' institution with re-RT were retrospectively reviewed. Treatment modalities for re-RT were intensity-modulated radiotherapy (n = 14), three-dimensional conformal radiotherapy (n = 9), single-fraction stereotactic radiosurgery (n = 6), fractionated stereotactic radiotherapy (n = 2), and high dose rate intracavitary brachytherapy (n = 1). Twenty-seven patients received re-RT with curative intent, whereas five patients were treated palliatively. RESULTS: Median follow-up time was 15.5 months (range, 1 to 123 months) for the entire cohort and 20 months (range, 3 to 123 months) for patients treated with curative intent. For the entire cohort, median locoregional recurrence-free survival (LRRFS) was 14 months, with actuarial 1- and 2-year LRRFS estimates of 67.5% and 44.0%, respectively. Median overall survival (OS) time was 38 months, with actuarial 1- and 2-year estimates of 74.2% and 57.2%, respectively. For patients treated with curative intent, median LRRFS was not reached. Actuarial 1- and 2-year LRRFS estimates were 68.2% and 54.5%, respectively. Median OS time after curative intent re-RT was 42 months, with actuarial 1- and 2-year estimates of 75.4% and 63.8%, respectively. One- and 2-year OS estimates based on risk stratification were 68.6% for high risk compared with 80.8% for low risk and 34.3% for high risk compared with 70.7% for low risk, respectively ( P = .223). Three patients (9.4%) developed symptomatic temporal lobe necrosis. There was no reported grade 5 treatment-related toxicity. CONCLUSION: Results of the study suggest that re-RT is an effective and safe salvage treatment strategy for rNPC. Re-RT to a maximum equivalent dose in 2-Gy fractions of 60 Gy may yield good LRRFS and translate to prolonged OS.