Mixtures of Regression Models for Time-Course Gene Expression Data: Evaluation of Initialization and Random Effects

Finite mixture models are routinely applied to time course microarray data. Due to the complexity and size of this type of data the choice of good starting values plays an important role. So far initialization strategies have only been investigated for data from a mixture of multivariate normal distributions. In this work several initialization procedures are evaluated for mixtures of regression models with and without random effects in an extensive simulation study on different artificial datasets. Finally these procedures are also applied to a real dataset from E. coli

Pregnancy outcomes in patients with autoimmune diseases and anti-Ro/SSA antibodies

Anti-Ro/SSA antibodies are associated with neonatal lupus (congenital heart block (CHB), neonatal transient skin rash, hematological and hepatic abnormalities), but do not negatively affects other gestational outcomes, and the general outcome of these pregnancies is now good, when followed by experienced multidisciplinary teams. The prevalence of CHB, defined as an atrioventricular block diagnosed in utero, at birth, or within the neonatal period (0-27 days after birth), in the offspring of an anti-Ro/SSA-positive women is 1-2%, of neonatal lupus rash around 10-20%, while laboratory abnormalities in asymptomatic babies can be detected in up to 27% of cases. The risk of recurrence of CHB is ten times higher. Most of the mothers are asymptomatic at delivery and are identified only by the birth of an affected child. Half of these asymptomatic women develop symptoms of a rheumatic disease, most commonly arthralgias and xerophtalmia, but few develop lupus nephritis. A standard therapy for CHB is still matter of investigation, although fluorinated corticosteroids have been reported to be effective for associated cardiomyopathy. Serial echocardiograms and obstetric sonograms, performed at least every 1-2 weeks starting from the 16th week of gestational age, are recommended in anti-Ro/SSA-positive pregnant women to detect early fetal abnormalities that might be a target of preventive therapy

Platelet-Rich Plasma combined with a sterile 3D polylactic acid scaffold for postoperative management of complete hoof wall resection for keratoma in four horses.

Keratoma is a non-malignant horse tumour that grows in the space between the horn of the hoof and the distal phalanx. Keratoma causes lameness in the horse, and surgical excision is the treatment of choice. Four horses underwent removal of a keratoma by complete hoof wall resection. The remaining wound was treated with Platelet-Rich Plasma (PRP) combined with a sterile 3D polylactic acid scaffold. The PRP was applied at 3, 6, 9, 12, 15 and 18 days postoperatively. The surgical site was cleaned with gauzes and swabs soaked in Ringer’s lactate solution before applying PRP and the foot bandage. Healthy granulation tissue developed at 6-21 days postoperatively. The hoof wall defect was completely filled with new hoof wall within 6-8 months after surgery. All horses returned to their previous exercise level and no recurrence of lameness was reported by the owner

Clinical Effects of the Extract of the Seeds of the Indian Celery-Apium Graveolens-In Horses Affected by Chronic Osteoarthritis.

The extract of the seeds from Indian celery, Apium greaveolens (CSE), tested in experimental animals (rodents), and in humans aected by chronic osteoarthritic diseases, exhibits anti-inflammatory eects that can be compared, to some degree, to those of non-steroid anti-inflammatory drugs (NSAID). In view of a potential use of CSE in the equine species, it was tested on horses aected by chronic articular pathologies. The trial was performed on 20 horses divided into three dierent groups, orally treated with 0 (controls), 7.0 or 30 g of CSE BID. Basic orthopedic examinations were conducted, vital signs were observed, and blood samples collected. Improvement was observed at the highest dosage tested (30 g of CSE BID), as reflected in the score values of three clinical parameters, (i) amplitude and (ii) sensitivity to passive flexion and (iii) flexion test. Since the improvement of these parameters can be correlated with a lower perception of the pain, the present data suggest that the CSE treatment can have an analgesic eect in horses aected by chronic osteoarthritic diseases

Nanoplastics impair in vitro swine granulosa cell functions

Soil, water and air pollution by plastic represents an issue of great concern since the particles produced by degradation of plastic materials can be ingested by animals and humans, with still uncertain health consequences. As a contribution on this crucial subject, the present work reports an investigation on the in vitro effects of different concentrations of polystyrene nanoplastics (5, 25 and 75 μg/mL) on swine granulosa cells, a model of endocrine reproductive cells. In particular, cell growth (BrDU incorporation and ATP production), steroidogenesis (17-β estradiol and progesterone secretion) and redox status (superoxide and nitric oxide production, enzymatic and non-enzymatic scavenging activity) were studied. Nanoplastics, at the highest concentration, stimulated cell proliferation (P < 0.05), while cell viability resulted unaffected. Steroidogenesis were disrupted (P < 0.05). Both enzymatic and non-enzymatic scavenging activity were increased after exposure at the highest nanoplastic dose (P < 0.05, P < 0.001). Nitric oxide secretion was increased by 25 and 75 μg/mL (P < 0.05) while superoxide generation was stimulated (P < 0.001) only by the highest concentration tested. Taken together, main features of cultured swine granulosa cells resulted affected by exposure to nanoplastics. These results raise concerns since environment nanoplastic contamination can represents a serious threat to animal and human health

Nearctic Pleistocene ungulates from the Pampean region (Argentina) in the historical collections of Santiago Roth in Switzerland: an overview

Nearctic ungulates such as artiodactyls, perissodactyls, and proboscideans arrived in South America during the Great American Biotic Interchange. Among them are camelids, cervids, tayassuids, equids, tapirids and gomphotherids. A historical collection of Nearctic ungulates from Pleistocene deposits of the Pampean region in Argentina is here studied and described. The collection consists of specimens collected by Santiago Roth in the nineteenth century and brought to Europe, where they are housed in the paleontological collections of the University of Zurich and the Natural History Museum of Geneva. Among the taxa reported here are Notiomastodon platensis,Lama guanicoe, Hemiauchenia paradoxa, Tayassu pecari, Morenelaphus sp., Hippidion cf. H. principale, Equus cf. E. neogeus, and other indeterminate gomphotherids, camelids, tayassuids, cervids, and equids. The exact stratigraphic position of these fossils collected more than 130 years ago is in many cases uncertain. The historical collection is still relevant for taxonomic studies and for offering new insights into palaeobiogeography and palaeobiology of mammalian fauna of the region during the Pleistocene

Passively acquired anti-SSA/Ro antibodies are required for congenital heart block following ovodonation but maternal genes are not

Anti-SSA/Ro antibodies are necessary but not sufficient to provoke autoimmune-associated congenital heart block (CHB). Genetic factors are likely contributory. Accordingly, HLA-related candidates and single-nucleotide polymorphisms in the promoter region of tumor necrosis factor alpha and codon 10 in transforming growth factor beta 1 (TGF beta 1) were evaluated in a unique family: the surrogate mother (anti-SSA/Ro positive), the biologic father, and the CHB-affected child (product of ovodonation). There was an HLA mismatch between the affected child and the surrogate mother. However, both the biologic and the surrogate mothers shared DQ2 and the profibrosing leucine polymorphism at codon 10 of TGF beta. In conclusion, we observed that CHB can develop in a genetically unrelated child exposed in utero to anti-SSA/Ro antibodies. Testing for anti-SSA/Ro antibodies might be considered in women undergoing artificial fertilization. It is possible that there is no direct association of maternal genes beyond a contributory role in generating the autoantibody

Canine mesenchymal cell lyosecretome production and safety evaluation after allogenic intraarticular injection in osteoarthritic dogs

In recent years, mesenchymal stromal cells (MSCs) have shown promise as a therapy in treating musculoskeletal diseases, and it is currently believed that their therapeutic effect is mainly related to the release of proteins and extracellular vesicles (EVs), known as secretome. In this work, three batches of canine MSC-secretome were prepared by standardized processes according to the current standard ISO9001 and formulated as a freeze-dried powder named Lyosecretome. The final products were char-acterized in protein and lipid content, EV size distribution and tested to ensure the microbiological safety required for intraarticular injection. Lyosecretome induced the proliferation of adipose tissue-derived canine MSCs, tenocytes, and chondrocytes in a dose-dependent manner and showed anti-elastase activ-ity, reaching 85% of inhibitory activity at a 20 mg/mL concentration. Finally, to evaluate the safety of the preparation, three patients affected by bilateral knee or elbow osteoarthritis were treated with two intraarticular injections (t = 0 and t = 40 days) of the allogeneic Lyosecretome (20 mg corresponding 2 × 106 cell equivalents) resuspended in hyaluronic acid in one joint and placebo (mannitol resuspended in hyalu-ronic acid) in the other joint. To establish the safety of the treatment, the follow-up included a questionnaire addressed to the owner and orthopaedic examinations to assess lameness grade, pain score, func-tional disability score and range of motion up to day 80 post-treatment. Overall, the collected data suggest that intra-articular injection of allogeneic Lyosecretome is safe and does not induce a clinically significant local or systemic adverse response