COVID-19 and andrology: Recommendations of the French-speaking society of andrology (Société d'Andrologie de langue Française SALF).

SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) metamorphosed our medical practice. In early June 2020, more than 6,400,000 COVID-19 (coronavirus-19 disease) cases were diagnosed across the world and more than 380,000 deaths were linked to COVID-19. Many medical symptoms of COVID-19 were reported. We will focus, here, on potential impacts of COVID-19 on men's andrological health. Our society (French-speaking society of andrology, SALF) also emitted some recommendations in the andrological management of men infected by SARS-CoV-2. First, considering the fever and the potential presence of SARS-CoV2 in semen, SALF recommends waiting for 3 months (duration of one spermatogenesis cycle and epididymal transit) before re-starting ART in the case of men diagnosed COVID-19 positive. Whatever the nature of testosterone and COVID-19 relationships, we recommend an andrological examination, sperm parameters, and hormonal evaluation at the time of the COVID-19 is diagnosed, and several months later. Furthermore, we are concerned by the potential morbid-mortality of the COVID-19, which mainly affects men. This "andrological bias", if proven, must be reduced by specific andrological diagnosis, therapeutic and prophylactic measures. Research in this direction must be substantiated and financially supported over the next few months (years).

Le SRAS-CoV-2 (nouveau coronavirus ou coronavirus numéro 2 responsable du syndrome respiratoire aigu sévère) a métamorphosé notre pratique médicale. Début juin 2020, plus de 6,400,000 cas de COVID-19 (maladie à coronavirus 2019) ont été diagnostiqués dans le monde et plus de 380,000 décès ont été reliés à cette maladie. De nombreux symptômes médicaux de cette infection virale ont été signalés. Nous nous concentrerons, ici, sur les impacts potentiels de COVID-19 sur la santé andrologique des hommes. Notre société (Société d'andrologie de langue Française, SALF) émet ici quelques recommandations dans la prise en charge andrologique des hommes infectés par le SRAS-CoV-2. Tout d'abord, compte tenu de la fièvre et de la présence potentielle du SRAS-CoV2 dans le sperme, la SALF recommande d'attendre 3 mois (durée d'un cycle de spermatogenèse et transit épididymaire) avant de recommencer les techniques d'assistance médicale à la procréation pour les hommes diagnostiqués COVID-19 positifs. Quelle que soit la nature des relations entre la testostérone et l'infection à SARS-CoV-2, nous recommandons un examen andrologique, un examen des paramètres du sperme et une évaluation hormonale au moment du diagnostic de l'infection, ainsi qu'à distance (3­6 mois plus tard). De plus, nous sommes préoccupés par la morbidité et la mortalité potentielles de l'infection COVID-19, qui touche principalement les hommes. Ce "biais andrologique", s'il est. prouvé, doit être réduit par un diagnostic andrologique spécifique et des mesures thérapeutiques et prophylactiques. La recherche dans ce sens doit être étayée et soutenue financièrement au cours des prochains mois (années).

[Do phosphodiesterase type 5 inhibitors generics enhance discontinuation due to price with patients suffering from erectile dysfunction?] / Les génériques d'inhibiteur de la 5 phosphodiestérase améliorent-ils l'observance au traitement en raison d'un coût moindre ?

INTRODUCTION: Phosphodiesterase type 5 inhibitors (PDE5i) are the first-line treatment of erectile dyfunction (ED). Cost of PDE5i is not covered by health insurance company in France. Few studies have examined the potential impact of the introduction of generic products of PDE5i on price non-compliance. The aim of the study was to compare the non-compliance rate because of price among patients treated for DE with generics of PDE5i and those treated with brand-name medications. METHOD: A multi-centre, cross-sectional, study that analyzed the answers to a questionnaire distributed to consultations in four hospitals for a period of twenty-eight months. Patients were included if they had DE treated for at least 3 months. The proportions between the two groups were compared with a non-inferiority test Wilcoxon-Mann-Whitney. RESULTS: One hundred and seventy-seven questionnaires were analyzed. Patients treated with generic PDE5i were significantly (α<0.05) as non-compliant because of price as patients treated with treated with brand-name PDE5i, respectively 34% (28/82) and 38% (36/95). The main causes of non-compliance were: high treatment costs, a lower than expected effect, lack of opportunity or sexual desire. The proportion of patients splitting the PDE5i tablet to achieve savings was 19% (33/177). To find the lowest price, 57% (101/177) of patients had consulted several pharmacies. These patients consulted 2.4±1.5 pharmacies. In the study population, 44% (78/177) of patients compared prices on commercial websites on the Internet. CONCLUSION: Patients treated with generic PDE5i are as unobservant as those treated with brand-name PDE5i. LEVEL OF EVIDENCE: 3.

[Treatment by stem cell therapy of erectile dysfunction of diabetic origin: State of the art]. / Traitement par les cellules souches de la dysfonction érectile d'origine diabétique : état des lieux.

PURPOSE: Review of various publications on stem cell therapy to treat erectile dysfunction of diabetic origin. MATERIAL AND METHODS: Bibliographic search in PUBMED performed using the keywords cell therapy strain/erectile dysfunction associated with diabetes. Among the 51 articles obtained from the PUBMED research, we selected 16 articles for their specificity of studying erectile dysfunction (DE) related to diabetes. RESULTS: Different types of stem cells have been studied: adipose derived mesenchymal stem cells/bone marrow derived mesenchymal stem cells as well as progenitor endothelial cells. The experimental protocols are quite similar from one study to the next with nevertheless some specifications concerning the studied cells and the monitoring of the latter. Intracavernous pressure (ICP) measured after the injection of stem cells into the corpus cavernosum was always significantly higher than the control populations. The addition of certain growth factors to stem cells by gene transfection improve the efficacy of the cells. No ideal tracking markers of the cells have been identified. CONCLUSION: The positive effect of the injection of stem cells on the ICP belongs to the cellular trans-differentiation effect but especially to the paracrine effects which have not yet been completely elucidated.

On simulating sustained isometric muscle fatigue: a phenomenological model considering different fiber metabolisms.

The present study shows a new computational FEM technique to simulate the evolution of the mechanical response of 3D muscle models subjected to fatigue. In an attempt to obtain very realistic models, parameters needed to adjust the mathematical formulation were obtained from in vivo experimental tests. The fatigue contractile properties of three different rat muscles (Tibialis Anterior, Extensor Digitorium Longus and Soleus) subjected to sustained maximal isometric contraction were determined. Experiments were conducted on three groups [Formula: see text] of male Wistar rats [Formula: see text] using a protocol previously developed by the authors for short tetanic contractions. The muscles were subjected to an electrical stimulus to achieve tetanic contraction during 10 s. The parameters obtained for each muscle were incorporated into a finite strain formulation for simulating active and passive behavior of muscles with different fiber metabolisms. The results show the potential of the model to predict muscle fatigue under high-frequency stimulation and the 3D distribution of mechanical variables such as stresses and strains.

Genetic diversity and differentiation of five Cuban cattle breeds using 30 microsatellite loci.

Conservation and improvement strategies in farm animals should be based on a combination of genetic and phenotypic characteristics. Genotype data from 30 microsatellites were used to assess the genetic diversity and relationships among five Cuban cattle breeds (Siboney de Cuba, Criollo Cubano, Cebú Cubano, Mambí de Cuba and Taíno de Cuba). All microsatellite markers were highly polymorphic in all the breeds. The expected heterozygosity ranged from 0.67 ± 0.02 in the Taíno de Cuba breed to 0.75 ± 0.02 in the Mambí de Cuba breed, and the observed heterozygosity ranged from 0.66 ± 0.03 in the Cebú Cubano breed to 0.73 ± 0.02 in the Siboney de Cuba breed. The genetic differentiation between the breeds was significant (p < 0.01) based on the infinitesimal model (F(ST)). The exact test for Hardy-Weinberg equilibrium within breeds showed a significant deviation in each breed (p < 0.0003) for one or more loci. The genetic distance and structure analysis showed that a significant amount of genetic variation is maintained in the local cattle population and that all breeds studied could be considered genetically distinct. The Siboney de Cuba and Mambí de Cuba breeds seem to be the most genetically related among the studied five breeds.

Stochastic cellular automata model of cell migration, proliferation and differentiation: validation with in vitro cultures of muscle satellite cells.

Cell migration and proliferation has been modelled in the literature as a process similar to diffusion. However, using diffusion models to simulate the proliferation and migration of cells tends to create a homogeneous distribution in the cell density that does not correlate to empirical observations. In fact, the mechanism of cell dispersal is not diffusion. Cells disperse by crawling or proliferation, or are transported in a moving fluid. The use of cellular automata, particle models or cell-based models can overcome this limitation. This paper presents a stochastic cellular automata model to simulate the proliferation, migration and differentiation of cells. These processes are considered as completely stochastic as well as discrete. The model developed was applied to predict the behaviour of in vitro cell cultures performed with adult muscle satellite cells. Moreover, non homogeneous distribution of cells has been observed inside the culture well and, using the above mentioned stochastic cellular automata model, we have been able to predict this heterogeneous cell distribution and compute accurate quantitative results. Differentiation was also incorporated into the computational simulation. The results predicted the myotube formation that typically occurs with adult muscle satellite cells. In conclusion, we have shown how a stochastic cellular automata model can be implemented and is capable of reproducing the in vitro behaviour of adult muscle satellite cells.

Comparative study of equine bone marrow and adipose tissue-derived mesenchymal stromal cells.

REASONS FOR PERFORMING STUDY: Mesenchymal stromal cells (MSCs) represent an attractive source for regenerative medicine. However, prior to their application, fundamental questions regarding molecular characterisation, growth and differentiation of MSCs must be resolved. OBJECTIVES: To compare and better understand the behaviour of equine MSCs obtained from bone marrow (BM) and adipose tissue (AT) in culture. METHODS: Five horses were included in this study. Proliferation rate was measured using MTT assay and cell viability; apoptosis, necrosis and late apoptosis and necrosis were evaluated by flow cytometry. The mRNA expression levels of 7 surface marker genes were quantified using RT-qPCR and CD90 was also analysed by flow cytometry. Differentiation was evaluated using specific staining, measurement of alkaline phosphatase activity and analysis of the mRNA expression. RESULTS: High interindividual differences were observed in proliferation in both cell types, particularly during the final days. Statistically significant differences in viability and early apoptosis of cultured AT- and BM-MSCs were found. The highest values of early apoptosis were observed during the first days of culture, while the highest percentage of necrosis and late apoptosis and lowest viability was observed in the last days. Surface marker expression pattern observed is in accordance to other studies in horse and other species. Osteogenic differentiation was evident after 7 days, with an increasing of ALP activity and mRNA expression of osteogenic markers. Adipogenic differentiation was achieved in BM-MSCs from 2 donors with one of the 16 media tested. Chondrogenic differentiation was also observed. CONCLUSIONS: Proliferation ability is different in AT-MSCs and BM-MSCs. Differences in viability and early apoptosis were observed between both sources and CD34 was only found in AT-MSCs. Differences in their osteogenic and adipogenic potential were detected by staining and quantification of specific tissue markers. POTENTIAL RELEVANCE: To provide data to better understand AT-MSCs and BM-MSCs behaviour in vitro.

A 3D active-passive numerical skeletal muscle model incorporating initial tissue strains. Validation with experimental results on rat tibialis anterior muscle.

This paper presents a three-dimensional finite element model of skeletal muscle and its validation incorporating inital tissue strains. A constitutive relation was determined by using a convex free strain energy function (SEF) where active and passive response contributions were obtained fitting experimental data from the rat tibialis anterior (TA) muscle. The passive and active finite strains response was modelled within the framework of continuum mechanics by a quasi-incompressible transversely isotropic material formulation. Magnetic resonance images (MRI) were obtained to reconstruct the external geometry of the TA. This geometry includes initial strains also taken into account in the numerical model. The numerical results show excellent agreement with the experimental results when comparing reaction force-extension curves both in passive and active tests. The proposed constitutive model for the muscle is implemented in a subroutine in the commercial finite element software package ABAQUS.

Active response of skeletal muscle: in vivo experimental results and model formulation.

The contractile properties of the tibial anterior (TA) of Wistar rats were measured by means of a multipurpose testing machine. The muscle was isolated from the connective tissues, preserving the proximal insertion. The distal tendon was transected and fixed to the machine actuator. The leg was inmobilised using a pin drilled through the femoral condyle. In this way the force response was studied in vivo at different constant lengths for some voltages and frequencies. Mathematical functions are proposed for adjusting the force-length, force-frequency and force-time relations. The model includes a novel formulation for the depression response during muscle tetanisation.

Passive nonlinear elastic behaviour of skeletal muscle: experimental results and model formulation.

The goal of this study was to characterize the passive elastic behaviour of muscle and tendon tissues of rat tibialis anterior. For that purpose, tissue samples from 3 month old female Wistar rats (210+/-11g) were mechanically tested in vitro. Moreover, an in vivo device was developed to measure the muscle-tendon unit response to increasing load. Mechanical tests, consisting of uniaxial loading along the longitudinal axis of tendon and muscle strips, revealed the nonlinear mechanical behaviour of these tissues. A material model was formulated and its parameters fit to the experimental data using the Levenberg-Marquardt optimization algorithm. The fit goodness was assessed and R(2) values close to 1 and very low epsilon values were obtained. The passive behaviour of a future finite element model of a muscle-tendon unit will be validated against the in vivo passive extension tests by comparing the reaction force-extension curves.

A genetic fusion GDNF-C fragment of tetanus toxin prolongs survival in a symptomatic mouse ALS model.

PURPOSE: Amyotrophic Lateral Sclerosis (ALS) is a paralyzing disorder that kills individuals within three to five years of onset without any possibility for effective treatment. One proposed therapy has been the use of neurotrophic factors to inhibit the apoptosis of motorneurones. At the present, one way to deliver neurotrophic factors after intramuscular injection to the motor neurones is through the use of adenoviral vectors. An alternative strategy is the use of the atoxic C fragment of tetanus toxin (TTC) as a neurotrophic factor carrier for motorneurones. METHODS: We have produced the recombinant protein fusion Glial Derived Neurotrophic Factor and C fragment of tetanus toxin (GDNF-TTC) and we have tested its antiapoptotic activity in degeneration culture cells and in the symptomatic SOD;{G93A} transgenic animal model for ALS. RESULTS: We demonstrated that GDNF-TTC induces the neuronal survival Akt kinase pathway in mouse cortical culture neurons and~maintains its antiapoptotic neuronal activity in Neuro2A cells. Moreover, we have found that genetic fusion is able to increase survival by 9 days and improves life quality in symptomatic ALS animal models. CONCLUSION: These results suggest that recombinant GDNF-TTC fusion protein intramuscular injections provide a potential therapy for ALS treatment.

An experimental study of the mouse skin behaviour: damage and inelastic aspects.

Samples of male and female mice skin were tested under monotonic and cyclic loading to mechanically characterize the tissue for large deformations. Cyclic tests have shown a typical Mullins effect widely known for elastomers and other soft tissues. No statistical difference was found in the maximum stretch of the sample after the fifth loading cycle for male (1.26 +/- 0.035) and female (1.18 +/- 0.083). However, larger dispersion was obtained for the maximum stress for both genders, 0.61 +/- 0.16 MPa for male and 0.78 +/- 0.32 MPa for female. Results show the presence of inelastic strain and stress softening in the skin at large deformations. They also have shown how stress softening and residual strain change with the magnitude of the applied load. Good correlation was observed between the residual strain and the maximum strain previously attained by the sample during loading for all samples. However, the correlation was different between genders.

Technical note: A quick and more sensitive method to identify pork in processed and unprocessed food by PCR amplification of a new specific DNA fragment.

We developed and evaluated a PCR procedure to detect pork in heated and unheated meat, sausages, canned food, cured products, and pâtés using a faster, more specific, and more sensitive method than others previously described. Isolation of a new DNA-specific porcine repetitive element was performed by nonspecific PCR amplification. After analyzing this repetitive sequence, a pair of primers were synthesized. To confirm the effectiveness and specificity of this fragment, 55 pig blood DNA samples (from differents breeds) were tested and positive results were obtained. With 200 samples tested from other species, the specific pork amplification was not detected. Using this method, we can partially quantify degree of contamination, depending on the PCR amplification cycles, detecting up to 0.005% pork in beef and 1% pork in duck pâté using 30 and 20 PCR amplification cycles, respectively. The amount of porcine DNA detected in cattle DNA was 1.25 and 250 pg when using 30 and 20 amplification cycles, respectively. Pork has been identified in both heated and unheated meat products, sausages, canned food, hamburgers, and pâtés. In conclusion, specific PCR amplification of a repetitive DNA element seems to be a powerful technique for the identification of pork in processed and unprocessed food, because of its simplicity, specificity, and sensitivity (with 30 amplification cycles we can detect 0.005% pork). Furthermore, it is a very fast method, because 1% pork contamination can be detected with 20 PCR cycles. The procedure is also much cheaper than other methods based on RFLP-PCR, immunodiffusion, or other techniques that need expensive equipment.

Random amplified polymorphic DNA fingerprints for identification of species in poultry pâté.

Because some fraudulent or unintentional mislabeling occurs that can be undetected, resulting in lower quality pâté, and because some population groups, for philosophical or religious reasons, do not wish to eat meat from certain species, a new procedure was developed and evaluated to detect pâté species composition by randomly amplified polymorphic DNA (RAPD). The RAPD method was used to generate fingerprint patterns for pork, chicken, duck, turkey, and goose meats. Ten DNA samples from pork, chicken, turkey, and duck meats were tested to confirm the effectiveness and specificity. Specific results for each species were obtained by the RAPD method. Sensitivity of the method was studied by DNA dilution in each species, detecting as little as 250 pg of DNA. Isolations of DNA from 30 pâtés (tinned and untinned) were carried out, and an optimal DNA was obtained for using as template DNA in polymerase chain reaction (PCR). The RAPD-PCR pattern was useful to identify species composition of pork, duck, duck-pork, goose, and poultry pâtés. This study demonstrates the usefulness of RAPD fingerprinting to distinguish between species in pâtés.