Taphonomical observations on the pygmy hippopotamus site in Aghia Napa, Cyprus.

Στην εργασία αυτή παρουσιάζονται τα αποτελέσματα ταφονομικής ανάλυσης της Άνω πλειστοκαινικής θέσης της Αγίας Νάπας στην Κύπρο. Η πανίδα της απολιθωματοφόρου θέσης κυριαρχείται από σκελετικό υλικό νάνων ιπποπόταμων του είδους Phanourios minor, και εντοπίζεται κάτω από ένα φυσικό στέγαστρο εντός των ασβεστολιθικών σχηματισμών της περιοχής. Η εμφάνιση εκτείνεται σε μια περιοχή περίπου 72 τ.μ. από την οποία έχει συλλεχθεί ιδιαίτερα μεγάλος αριθμός ευρημάτων που υποδεικνύει την ύπαρξη περισσότερων από 160 ιπποπόταμων στη θέση. Στόχο της μελέτης αποτελεί και η απόδοση της αυξημένης συσσώρευσης του οστεολογικού υλικού σε συγκεκριμένους μηχανισμούς, εστιάζοντας στους παλαιοπεριβαλλοντικούς παράγοντες που πιθανά έχουν επηρεάσει και την επιβίωση του. Η ανάλυση στηρίζεται και σε παραμέτρους που μας πληροφορούν σχετικά με την αντιπροσώπευση και άρα την επιβίωση των διαφόρων σκελετικών στοιχείων. Η μελέτη του υλικού ανέδειξε την ύπαρξη λείανσης, κατακερματισμού και σημαντικής θραύσης, φαινόμενα που σχετίζονται με τον τύπο, το μέγεθος και το σχήμα των σκελετικών στοιχείων. Η συσσώρευση του υπό μελέτη υλικού ερμηνεύεται ως αποτέλεσμα φυσικής μεταφοράς τους στη θέση από την γύρω περιοχή, ενώ ο ρόλος του ανθρώπου σε αυτήν είναι ακόμη υπό διερεύνηση. In this paper data concerning the taphonomy of the Upper Pleistocene site Aghia Napa in Cyprus is presented. The site is dominated by skeletal material belonging to the pygmy Hippopotamus species Phanourios minor, and consists a littoral rockshelter. The fossiliferous assemblage is spread in a total area of about 72 m2 and a significantly large number of specimens were collected, indicating the presence of more than 160 individuals at the site. In this paper, we attempt to identify the causes or mechanisms that led to the accumulation of the endemic hippopotamus remains, focusing also on the palaeo-environmental parameters that might had affected the survivorship of the fossils. The taphonomical analysis is also based on parameters, which provide information concerning skeletal element representation and thus survivorship. The study of the skeletal material shows signs of abrasion, cracking and significant fragmentation which are related to the type, size and shape of the skeletal elements. The bone assemblage is interpreted as a result of transportation of the skeletal material from longer or shorter distances in the surrounding area while the impact of man concerning their accumulation is still under discussion

Pain management of a mandibular fracture in an alpaca (Vicugna pacos) via epidural catheter placement in the mandibular foramen

A nine-year-old female alpaca with a history of a recurrent tooth root abscess presented for further investigation of a swelling of the left mandible and possible tooth extraction. During the manipulation of the mandible in surgery, the mandibular body fractured, and due to active infection it was left to heal by secondary intention. After surgery, the alpaca became dull and inappetent. Analgesic drugs included buprenorphine and meloxicam, which were ineffective according to the alpaca’s clinical appearance. An inferior alveolar nerve block was achieved by repeated administration of local anaesthetic (ropivacaine 0.75 per cent) every six hours via an epidural catheter placed in the mandibular foramen under CT guidance. Despite the adequate level of comfort achieved, discharge from surgical site resumed and the owner elected euthanasia. In conclusion, the placement of an epidural catheter in the mandibular canal, under CT guidance, was proven to successfully provide analgesia to an alpaca suffering from mandibular fractures

Gene editing restores dystrophin expression in a canine model of Duchenne muscular dystrophy

Mutations in the gene encoding dystrophin, a protein that maintains muscle integrity and function, cause Duchenne muscular dystrophy (DMD). The deltaE50-MD dog model of DMD harbors a mutation corresponding to a mutational “hotspot” in the human DMD gene. We used adeno-associated viruses to deliver CRISPR gene editing components to four dogs and examined dystrophin protein expression 6 weeks after intramuscular delivery (n = 2) or 8 weeks after systemic delivery (n = 2). After systemic delivery in skeletal muscle, dystrophin was restored to levels ranging from 3 to 90% of normal, depending on muscle type. In cardiac muscle, dystrophin levels in the dog receiving the highest dose reached 92% of normal. The treated dogs also showed improved muscle histology. These large-animal data support the concept that, with further development, gene editing approaches may prove clinically useful for the treatment of DMD

Electrode fabrication and interface optimization for imaging of evoked peripheral nervous system activity with electrical impedance tomography (EIT)

Objective. Non-invasive imaging techniques are undoubtedly the ideal methods for continuous monitoring of neural activity. One such method, fast neural electrical impedance tomography (EIT) has been developed over the past decade in order to image neural action potentials with non-penetrating electrode arrays. Approach. The goal of this study is two-fold. First, we present a detailed fabrication method for silicone-based multiple electrode arrays which can be used for epicortical or neural cuff applications. Secondly, we optimize electrode material coatings in order to achieve the best accuracy in EIT reconstructions. Main results. The testing of nanostructured electrode interface materials consisting of platinum, iridium oxide, and PEDOT:pTS in saline tank experiments demonstrated that the PEDOT:pTS coating used in this study leads to more accurate reconstruction dimensions along with reduced phase separation between recording channels. The PEDOT:pTS electrodes were then used in vivo to successfully image and localize the evoked activity of the recurrent laryngeal fascicle from within the cervical vagus nerve. Significance. These results alongside the simple fabrication method presented here position EIT as an effective method to image neural activity

Deleterious Effects of Cold Air Inhalation on Coronary Physiological Indices in Patients With Obstructive Coronary Artery Disease

Background Cold air inhalation during exercise increases cardiac mortality, but the pathophysiology is unclear. During cold and exercise, dual‐sensor intracoronary wires measured coronary microvascular resistance (MVR) and blood flow velocity (CBF), and cardiac magnetic resonance measured subendocardial perfusion. Methods and Results Forty‐two patients (62±9 years) undergoing cardiac catheterization, 32 with obstructive coronary stenoses and 10 without, performed either (1) 5 minutes of cold air inhalation (5°F) or (2) two 5‐minute supine‐cycling periods: 1 at room temperature and 1 during cold air inhalation (5°F) (randomized order). We compared rest and peak stress MVR, CBF, and subendocardial perfusion measurements. In patients with unobstructed coronary arteries (n=10), cold air inhalation at rest decreased MVR by 6% (P=0.41), increasing CBF by 20% (P<0.01). However, in patients with obstructive stenoses (n=10), cold air inhalation at rest increased MVR by 17% (P<0.01), reducing CBF by 3% (P=0.85). Consequently, in patients with obstructive stenoses undergoing the cardiac magnetic resonance protocol (n=10), cold air inhalation reduced subendocardial perfusion (P<0.05). Only patients with obstructive stenoses performed this protocol (n=12). Cycling at room temperature decreased MVR by 29% (P<0.001) and increased CBF by 61% (P<0.001). However, cold air inhalation during cycling blunted these adaptations in MVR (P=0.12) and CBF (P<0.05), an effect attributable to defective early diastolic CBF acceleration (P<0.05) and associated with greater ST‐segment depression (P<0.05). Conclusions In patients with obstructive coronary stenoses, cold air inhalation causes deleterious changes in MVR and CBF. These diminish or abolish the normal adaptations during exertion that ordinarily match myocardial blood supply to demand

VEGF-related polymorphisms identified by GWAS and risk for major depression

La depresión es una enfermedad mental común, grave e incapacitante que afecta a millones de personas de todas las edades en todo el mundo. Varios estudios han demostrado que los factores neurotróficos / de crecimiento tienen un papel clave en la depresión y, más específicamente, el factor de crecimiento endotelial vascular (VEGF) está implicado en la patogénesis de la depresión. El propósito de este estudio fue investigar los posibles vínculos entre cuatro polimorfismos de un solo nucleótido (SNP) relacionados con VEGF, previamente identificados a través de un estudio de asociación de genoma completo (GWAS) y la depresión. Los efectos directos y las interacciones epistáticas de los cuatro SNP relacionados con VEGF (rs10738760, rs6921438, rs6993770 y rs4416670) sobre la depresión se investigaron a través de un estudio de casos y controles que incluyó a 437 personas diagnosticadas con depresión y 477 voluntarios sanos como controles. El sexo, la edad y la influencia del índice de masa corporal se analizaron adicionalmente. El SNP rs4416670 se asoció con un mayor riesgo de depresión (OR: 1.60, P: 0.010). Este resultado demuestra la existencia de relaciones entre los determinantes genéticos del VEGF y la depresión. Esta novedosa asociación revela nuevos mecanismos moleculares que sugieren el papel potencial del VEGF en el desarrollo de la depresión que podría ayudar a promover una predicción personalizada para esta enfermedad común grave.Depression is a common, severe, disabling mental disease that affects millions of people of all ages worldwide. Various studies have shown that neurotrophic/growth factors have a key role in depression and, more specifically, vascular endothelial growth factor (VEGF) is implicated in the pathogenesis of depression. The purpose of this study was to investigate the potential links between four VEGF-related single-nucleotide polymorphisms (SNPs), previously identified through a genome-wide association study (GWAS) and depression. The direct effects and epistatic interactions of the four VEGF-related SNPs (rs10738760, rs6921438, rs6993770 and rs4416670) on depression were investigated through a case–control study including 437 individuals diagnosed with depression and 477 healthy volunteers as controls. Gender, age and body mass index influence was additionally analyzed. The SNP rs4416670 was associated with increased risk for depression (OR: 1.60, P: 0.010). This result demonstrates the existence of relationships between VEGF genetic determinants and depression. This novel association reveals new molecular mechanisms suggesting the potential role of VEGF in depression development that could help to promote a personalized prediction for this severe common disease.• Région Lorraine y Fondo Social Europeo. Ayuda • Junta de Extremadura. Ayuda TE14002, para Áura Delgado Regalado • Instituto de Salud Carlos III. Programa Sara Borrell. Proyecto CD13/00348, para Fernando de Andrés SegurapeerReviewe

Gene expression profile of circulating tumor cells in breast cancer by RT-qPCR

<p>Abstract</p> <p>Background</p> <p>Circulating tumor cells (CTCs) have been associated with prognosis especially in breast cancer and have been proposed as a liquid biopsy for repeated follow up examinations. Molecular characterization of CTCs is difficult to address since they are very rare and the amount of available sample is very limited.</p> <p>Methods</p> <p>We quantified by RT-qPCR <it>CK-19, MAGE-A3, HER-2, TWIST1, hTERT α+β+</it>, and <it>mammaglobin </it>gene transcripts in immunomagnetically positively selected CTCs from 92 breast cancer patients, and 28 healthy individuals. We also compared our results with the CellSearch system in 33 of these patients with early breast cancer.</p> <p>Results</p> <p>RT-qPCR is highly sensitive and specific and can detect the expression of each individual gene at the one cell level. None of the genes tested was detected in the group of healthy donors. In 66 operable breast cancer patients, <it>CK-19 </it>was detected in 42.4%, <it>HER-2 </it>in 13.6%, <it>MAGE-A3 </it>in 21.2%, <it>hMAM </it>in 13.6%, <it>TWIST-1 </it>in 42.4%, and <it>hTERT α+β+ </it>in 10.2%. In 26 patients with verified metastasis, <it>CK-19 </it>was detected in 53.8%, <it>HER-2 </it>in 19.2%, <it>MAGE-A3 </it>in 15.4%, <it>hMAM </it>in 30.8%, <it>TWIST-1 </it>in 38.5% and <it>hTERT </it>α⁺β⁺in 19.2%. Our preliminary data on the comparison between RT-qPCR and CellSearch in 33 early breast cancer patients showed that RT-qPCR gives more positive results in respect to CellSearch.</p> <p>Conclusions</p> <p>Molecular characterization of CTCs has revealed a remarkable heterogeneity of gene expression between breast cancer patients. In a small percentage of patients, CTCs were positive for all six genes tested, while in some patients only one of these genes was expressed. The clinical significance of these findings in early breast cancer remains to be elucidated when the clinical outcome for these patients is known.</p