Impaired spermatogenesis in Finnish boars and bulls

Maintenance of breeding efficiency and high semen quality is essential for reproductive success in farm animals. Early recognition of possible inheritable factors causing infertility requires constant attention. This thesis focuses on describing different manifestations of impaired spermatogenesis, their impact on fertility and partly also their incidence in populations. The reasons for spermatogenic failure are various. An interruption of germ cell differentiation, spermatogenic arrest, can lead to infertility. The incidence of azoospermia was investigated in the 1996 2005 survey of Finnish AI and farm breeding boars. We focused on the diagnosis, testicular morphometry and the possible reasons for the condition. The incidence of azoospermia was significantly higher in Yorkshire boars than in the Landrace breed. The most common diagnosis in Yorkshire boars was germ cell arrest at the primary spermatocyte level. The second most frequent diagnosis in Yorkshire boars was segmental aplasia of the Wolffian ducts with idiopathic epididymal obstruction. Other reasons for azoospermia were infrequent. In the second study we investigated the incidence of two relatively well-defined specific sperm defects in Finnish Yorkshire and Landrace boars during the same survey, the immotile short-tail sperm (ISTS) defect and the knobbed acrosome (KA) defect. In the Finnish Yorkshire boars the inherited ISTS defect, and the probably inherited KA defect, were important causes of infertility during 1996 2005. The ISTS defect was found in 7.6% and the KA defect in 0.8% of the Yorkshire boars. No Landrace boars were diagnosed with either of these two defects. In the third study we described a new sterilizing sperm defect in an oligoasthenoterazoospermic bull. Because of its morphological characteristics this defect was termed the multinuclear-multiflagellar sperm (MNMFS) defect. The number of Sertoli cells in the seminiferous tubuli was highly increased in the MNMFS bull compared with the number in normal bulls. In the following two studies we used a combined approach of fluorescence in situ hybridization (FISH), flow cytometry and morphometric studies to provide information on the cytogenetic background of macrocephalic bull spermatozoa. We described cellular features of diploid spermatozoa and compared the failures in the first and second meiotic divisions. In the last study we describe how the transplantation of testicular cells was used to determine whether spermatogonia derived from donor animals are able to colonize and produce motile spermatozoa in immune-competent unrelated boars suffering the ISTS defect. Transplantation resulted in complete focal spermatogenesis, indicated by the appearance of motile spermatozoa and confirmed by genotyping.Hyvä lisääntymiskyky ja sperman laatu ovat tärkeitä menestykselliselle kotieläintuotannolle. Perinnöllisten lisääntymishäiriöiden varhainen tunnistaminen vaatii jatkuvaa seurantaa. Tässä väitöskirjassa keskitytään kuvaamaan erilaisia häiriöitä siittiöiden kehityksessä, niiden vaikutusta hedelmällisyyteen ja osittain myös niiden esiintymiseen eri populaatioissa. Ensimmäisessä tutkimuksessa selvitettiin hedelmällisyyshäiriöiden esiintyvyyttä vuosina 1996 2005 suomalaisilla keinosiemennyskarjuilla ja tiloilla luonnollisesti astuvilla karjuilla. Tutkimuksessa keskityttiin diagnosointiin, kiveskudoksen rakenteiden mittaamiseen sekä häiriöiden mahdollisten syiden selvittämiseen. Siittiöiden kehityshäiriöitä esiintyi selvästi enemmän Yorkshire- kuin maatiasrotuisilla karjuilla. Yleisin diagnoosi Yorkshire-karjuilla oli siittiöiden kehityksen pysähtymien primaaristen spermatosyyttien tasolle. Toiseksi yleisimmin tavattiin Wolffin tiehyiden segmentaalista aplasiaa. Toisessa tutkimuksessa selvitettiin kahden jo aiemmin tunnetun siittiövian, puolihäntäsiittiövian (ISTS, the immotile short-tail sperm defect) ja akrosomivian (the knobbed acrosome defect, KA) esiintyvyyttä samassa aineistossa. Suomalaisilla Yorksire-karjuilla perinnöllinen ISTS-vika ja luultavasti perinnöllinen KA-vika olivat tärkeitä hedelmättömyyden syitä tutkitulla ajanjaksolla. ISTS todettiin 7.6 %:lla ja KA 0.8 %:lla Yorkshire-karjuista. Yhdelläkään maatiaisrotuisella karjulla ei todettu kumpaakaan näistä vioista. Kolmannessa tutkimuksessa kuvasimme keinosiemennyssonnilla täydellisen steriliteetin aiheuttavan siittiövian, oligoasthenoteratozoospermian. Siittiöiden morfologisten piirteiden perusteella häiriö nimettiin monituma-monihäntä-siittiöviaksi (the multinuclear-multiflagellar sperm defect, MNMFS). Histologisesti kiveskudoksessa tällä sonnilla Sertolin solujen lukumäärä oli selvästi suurempi kuin normaaleilla verrokeilla. Seuraavissa kahdessa tutkimuksessa käytettiin FISH-tekniikkaa (fluorescence in situ hybridization), virtaussytometriaa sekä morfometrisiä mittauksia tutkittaessa suuripäisten siittiöiden sytogenetiikkaa. Tutkimuksissa kuvattiin diploidien siittiöiden ominaisuuksia ja vertailtiin erilaisia meioosihäiriöitä niiden taustalla. Viimeisessä tutkimuksessa kuvasimme kuinka terveiden karjujen siittiöiden kantasoluja voidaan siirtää lisääntymiskyvyttömän ISTS karjun kiveksiin ja saada ne tuottamaan normaaleja siittiöitä luovuttajan kantasoluista

Immunopathologic Features of Allergic Contact Dermatitis in Humans: Participation of Plasmacytoid Dendritic Cells in the Pathogenesis of the Disease?

Contrary to our abundant knowledge about the sensitization phase of human contact hypersensitivity, little is known about the cell types orchestrating the effector phase. In order to address this issue, we phenotypically analyzed biopsies from 72 h epicutaneous patch test reactions (n=10) and normal human skin (n=5) for the presence of various leukocyte differentiation antigens. The inflammatory infiltrate was dominated by CD3+/CD4+ T cells with approximately 30% of the cells coexpressing CD25 and CTLA-4, a phenotype consistent with either activated effector or regulatory T cells. In our search for professional antigen-presenting cells, we were surprised to find not only sizeable numbers of CD1a+ dendritic cells and CD1c+ dendritic cells, but also of CD123+, CD45RA+, BDCA-2+, CLA+, and CD62L+ plasmacytoid dendritic cells. Although virtually absent in normal human skin, these cells were detectable already 6 h after hapten challenge and were often found in close proximity to CD56+ natural killer cells, indicative of a functional interaction between these cell types. The detailed knowledge of the cellular composition of the inflammatory infiltrate in allergic contact dermatitis and its kinetics should form the basis for the investigation of the immunologic and molecular events operative in the perpetuation and resolution of the eczematous response

Anti-glycoprotein VI mediated immune thrombocytopenia: An under-recognized and significant entity?

Idiopathic immune thrombocytopenia (ITP) is an autoimmune disorder characterized by relapsing/remitting thrombocytopenia. Bleeding complications are infrequent with platelet counts above 30x10(9)/L, and this level is commonly used as a threshold for treatment. The question of another/co-existent diagnosis or an alternate mechanism of platelet destruction arises when bleeding is experienced with platelet counts above this threshold. We report a case of anti-GPVI mediated ITP that was diagnosed following investigations performed to address this key clinical question. A patient with ITP experienced exaggerated bruising symptoms despite a platelet count of 91x10(9)/L. Platelet functional testing showed an isolated platelet defect of collagen-induced aggregation. Next generation sequencing excluded a pathogenic variant of GP6, and anti-GPVI antibodies that curtailed GPVI function were confirmed by extended platelet phenotyping. We propose that anti-GPVI mediated ITP may be under-recognized, and that inclusion of GPVI in antibody detection assays may improve their diagnostic utility and in turn, facilitate a better understanding of ITP pathophysiology and aid individualized treatment approaches

The antiferromagnetic insulator Ca3FeRhO6: characterization and electronic structure calculations

We investigate the antiferromagnetic insulating nature of Ca3FeRhO6 both experimentally and theoretically. Susceptibility measurements reveal a Neel temperature T_N = 20 K, and a magnetic moment of 5.3 muB/f. u., while Moessbauer spectroscopy strongly suggests that the Fe ions, located in trigonal prismatic sites, are in a 3+ high spin state. Transport measurements display a simple Arrhenius law, with an activation energy of 0.2 eV. The experimental results are interpreted with LSDA band structure calculations, which confirm the Fe 3+ state, the high-spin/low-spin scenario, the antiferromagnetic ordering, and the value for the activation energy.Comment: 5 pages, 6 figure

DNA-based Diagnosis of Uncharacterized Inherited Macrothrombocytopenias Using Next-generation Sequencing Technology with a Candidate Gene Array

Inherited macrothrombocytopenias comprise a heterogeneous group of inherited platelet disorders that are characterized by large platelets, thrombocytopenia and bleeding tendencies in affected individuals. Diagnostic platforms have traditionally involved a battery of complex phenotypic tests that often fail to reach a diagnosis. Next-generation sequencing lacks the pre-analytical and analytical shortcoming of these tests and provides an attractive alternate diagnostic approach. Our group has developed a candidate gene array targeting genes known to affect platelet function and tested it in a large cohort of Australasian patients with presumed platelet function disorders, particularly macrothrombocytopenia. This array identified causative variants in a significant portion of patients with uncharacterized platelet disorders, including transcription factor mutations that cannot easily be diagnosed with standard platelet phenotyping procedures. We propose that targeted genotypic screening can identify the genetic basis of platelet function defects and has the potential to be developed into a powerful clinical platform to help clinicians diagnose these rare disorders

Towards a layered framework for embodied language processing in situated human-robot interaction

Priesters M, Schilling M, Kopp S. Towards a layered framework for embodied language processing in situated human-robot interaction. In: Howes C, Larsson S, eds. Proceedings of the 19th Workshop on the Semantics and Pragmatics of Dialogue. Gothenburg: University of Gothenburg; 2015: 206-207

Impact of whole-body computed tomography on mortality and surgical management of severe blunt trauma

International audienceIntroductionThe mortality benefit of whole-body computed tomography (CT) in early trauma management remains controversial and poorly understood. The objective of this study was to assess the impact of whole-body CT compared with selective CT on mortality and management of patients with severe blunt trauma.MethodsThe FIRST (French Intensive care Recorded in Severe Trauma) study is a multicenter cohort study on consecutive patients with severe blunt trauma requiring admission to intensive care units from university hospital trauma centers within the first 72 hours. Initial data were combined to construct a propensity score to receive whole-body CT and selective CT used in multivariable logistic regression models, and to calculate the probability of survival according to the Trauma and Injury Severity Score (TRISS) for 1,950 patients. The main endpoint was 30-day mortality.ResultsIn total, 1,696 patients out of 1,950 (87%) were given whole-body CT. The crude 30-day mortality rates were 16% among whole-body CT patients and 22% among selective CT patients (p = 0.02). A significant reduction in the mortality risk was observed among whole-body CT patients whatever the adjustment method (OR = 0.58, 95% CI: 0.34-0.99 after adjustment for baseline characteristics and post-CT treatment). Compared to the TRISS predicted survival, survival significantly improved for whole-body CT patients but not for selective CT patients. The pattern of early surgical and medical procedures significantly differed between the two groups.ConclusionsDiagnostic whole-body CT was associated with a significant reduction in 30-day mortality among patients with severe blunt trauma. Its use may be a global indicator of better management

Risk Assessment Models for Venous Thromboembolism in Medical Inpatients.

IMPORTANCE Thromboprophylaxis is recommended for medical inpatients at risk of venous thromboembolism (VTE). Risk assessment models (RAMs) have been developed to stratify VTE risk, but a prospective head-to-head comparison of validated RAMs is lacking. OBJECTIVES To prospectively validate an easy-to-use RAM, the simplified Geneva score, and compare its prognostic performance with previously validated RAMs. DESIGN, SETTING, AND PARTICIPANTS This prospective cohort study was conducted from June 18, 2020, to January 4, 2022, with a 90-day follow-up. A total of 4205 consecutive adults admitted to the general internal medicine departments of 3 Swiss university hospitals for hospitalization for more than 24 hours due to acute illness were screened for eligibility; 1352 without therapeutic anticoagulation were included. EXPOSURES At admission, items of 4 RAMs (ie, the simplified and original Geneva score, the Padua score, and the IMPROVE [International Medical Prevention Registry on Venous Thromboembolism] score) were collected. Patients were stratified into high and low VTE risk groups according to each RAM. MAIN OUTCOMES AND MEASURES Symptomatic VTE within 90 days. RESULTS Of 1352 medical inpatients (median age, 67 years [IQR, 54-77 years]; 762 men [55.4%]), 28 (2.1%) experienced VTE. Based on the simplified Geneva score, 854 patients (63.2%) were classified as high risk, with a 90-day VTE risk of 2.6% (n = 22; 95% CI, 1.7%-3.9%), and 498 patients (36.8%) were classified as low risk, with a 90-day VTE risk of 1.2% (n = 6; 95% CI, 0.6%-2.6%). Sensitivity of the simplified Geneva score was 78.6% (95% CI, 60.5%-89.8%) and specificity was 37.2% (95% CI, 34.6%-39.8%); the positive likelihood ratio of the simplified Geneva score was 1.25 (95% CI, 1.03-1.52) and the negative likelihood ratio was 0.58 (95% CI, 0.28-1.18). In head-to-head comparisons, sensitivity was highest for the original Geneva score (82.1%; 95% CI, 64.4%-92.1%), while specificity was highest for the IMPROVE score (70.4%; 95% CI, 67.9%-72.8%). After adjusting the VTE risk for thromboprophylaxis use and site, there was no significant difference between the high-risk and low-risk groups based on the simplified Geneva score (subhazard ratio, 2.04 [95% CI, 0.83-5.05]; P = .12) and other RAMs. Discriminative performance was poor for all RAMs, with an area under the receiver operating characteristic curve ranging from 53.8% (95% CI, 51.1%-56.5%) for the original Geneva score to 58.1% (95% CI, 55.4%-60.7%) for the simplified Geneva score. CONCLUSIONS AND RELEVANCE This head-to-head comparison of validated RAMs found suboptimal accuracy and prognostic performance of the simplified Geneva score and other RAMs to predict hospital-acquired VTE in medical inpatients. Clinical usefulness of existing RAMs is questionable, highlighting the need for more accurate VTE prediction strategies

Overuse and underuse of thromboprophylaxis in medical inpatients.

Background Thromboprophylaxis (TPX) prescription is recommended in medical inpatients categorized as high risk of venous thromboembolism (VTE) by validated risk assessment models (RAMs), but how various RAMs differ in categorizing patients in risk groups, and whether the choice of RAM influences estimates of appropriate TPX use is unknown. Objectives To determine the proportion of medical inpatients categorized as high or low risk according to validated RAMs, and to investigate the appropriateness of TPX prescription. Methods This is a prospective cohort study of acutely ill medical inpatients from three Swiss university hospitals. Participants were categorized as high or low risk of VTE by validated RAMs (i.e., the Padua, IMPROVE, simplified, and original Geneva score). We assessed prescription of any TPX at baseline. We considered TPX prescription in high-risk and no TPX prescription in low-risk patients as appropriate. Results Among 1352 medical inpatients, the proportion categorized as high risk ranged from 29.8% with the IMPROVE to 66.1% with the original Geneva score. Overall, 24.6% were consistently categorized as high risk, and 26.3% as low risk by all four RAMs. Depending on the RAM used, TPX prescription was appropriate in 58.7-63.3% of high-risk (i.e., 36.7-41.3% underuse) and 52.4-62.8% of low-risk patients (i.e., 37.2-47.6% overuse). Conclusion The proportion of medical inpatients considered as high or low VTE risk varied widely according to different RAMs. Only half of patients were consistently categorized in the same risk group by all RAMs. While TPX remains underused in high-risk patients, overuse in low-risk patients is even more pronounced