Bruton's tyrosine kinase (BTK) is essential for B-cell proliferation/differentiation and it is generally believed that its expression and function are limited to bone marrow-derived cells. Here, we report the identification and characterization of p65BTK, a novel isoform abundantly expressed in colon carcinoma cell lines and tumour tissue samples. p65BTK protein is expressed, through heterogeneous nuclear ribonucleoprotein K (hnRNPK)-dependent and internal ribosome entry site-driven translation, from a transcript containing an alternative first exon in the 5′-untranslated region, and is post-transcriptionally regulated, via hnRNPK, by the mitogen-activated protein kinase (MAPK) pathway. p65BTK is endowed with strong transforming activity that depends on active signal-regulated protein kinases-1/2 (ERK1/2) and its inhibition abolishes RAS transforming activity. Accordingly, p65BTK overexpression in colon cancer tissues correlates with ERK1/2 activation. Moreover, p65BTK inhibition affects growth and survival of colon cancer cells. Our data reveal that BTK, via p65BTK expression, is a novel and powerful oncogene acting downstream of the RAS/MAPK pathway and suggest that its targeting may be a promising therapeutic approach.

The greater amberjack, (Risso, 1810), is a promising candidate for the diversification of European aquaculture production, but inconsistent reproduction in captivity prevents commercial production. Recent studies showed that greater amberjack confined in sea cages exhibited scarce gonad development and early interruption of gametogenic activity during the reproductive season. The aim of the present study was to improve our understanding of the observed impairment of spermatogenesis. Adult wild and captive-reared males were sampled during 3 different phases of the reproductive cycle: early gametogenesis (EARLY; late April to early May), advanced gametogenesis (ADVANCED; late May to early June), and spawning (SPAWNING; late June to July). Spermatogonial stem cells and proliferating germ cells were identified through the immunohistochemical localization of and proliferating cell nuclear antigen, respectively. Apoptotic germ cells were identified throughout the terminal deoxynucleotidyl transferase-mediated 2'-deoxyuridine 5'-triphosphate nick end labeling method. Sperm quality of captive-reared fish was evaluated using computer-assisted sperm analysis. Captive-reared males exhibited seminiferous lobules of a smaller diameter, a precocious and progressive decrease of spermatogonial mitosis, and a high level of apoptosis at the beginning of the reproductive season, concomitant with a many-fold higher 17β-estradiol plasma concentration. The motile spermatozoa percentage of captive greater amberjack was lower than in other teleosts, and a drastic decrease of spermatozoa motility duration, velocity, and ATP content occurred along the reproductive season. An abnormal increase of sperm concentration as well as an increase of dead spermatozoa occurred during the SPAWNING phase, probably because of lack of sperm hydration and ejaculation and consequent sperm ageing. The present study demonstrates the extreme susceptibility of greater amberjack to rearing stress and underscores the need for improvement of the rearing and handling procedures to ameliorate gametogenesis dysfunctions in commercial aquaculture production.

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Objectives: The present study aimed to demonstrate the efficacy of splash block using lidocaine to provide additional analgesia during ovariectomy in bitches. To identify an acute intraoperative nociceptive response, three clinical parameters were used: increased blood pressure, heart rate and respiratory rate.Material and Methods: Forty healthy bitches were randomly assigned to receive 2% lidocaine (L group) topical application (splash block) on both ovaries (2 mg/kg each), or an equal volume of NaCl 0.9% at the same sites (C group). A fentanyl bolus (2 µg/kg) was administered intraoperatively in response to an increase in blood pressure, heart rate or respiratory rate during surgery (> 30% compared with the pre-incisional values). Results:Local lidocaine administration significantly reduced the need for supplementary fentanyl. Dogs in the L group showed greater intraoperative hemodynamic stability and lower surgical pain than those in the C group. In addition to the routine anaesthetic protocol, the local anaesthesia used in the present study was safe and caused no cardiopulmonary suppression. In addition, it significantly reduced the need for mandatory systemic or rescue analgesia.Clinical Significance: Ovariectomy is a common surgical procedure in bitches. Analgesia during this procedure is important because intraoperative pain can cause negative effects that prevent patient recovery. This study aimed to demonstrate the analgesic efficacy of lidocaine splash block in video-assisted ovariectomy in dogs. The results showed that splash block improved surgical analgesia during canine laparoscopic ovariectomy. Considering its relative simplicity, low cost, and safety, splash block could be used in daily clinical practice.

Orchiectomy is a common surgical procedure performed on small animals, and it requires postoperative pain management despite its relative simplicity. This study aimed to evaluate the hemodynamic stability, intraoperative administration of additional hypnotic and/or analgesic drugs, and postoperative pain scores following the combination of ultrasound-guided injection of ropivacaine hydrochloride into the spermatic cord and infiltration by the same anaesthetic of the incisional prescrotal line (ROP) or general anaesthesia. Dogs in the ROP group showed greater intraoperative hemodynamic stability and lower pain scores than the control group. The locoregional approach used in this study proved effective in minimising the responses to the surgical stimulus and ensured adequate analgesia intra- and postoperatively. This method, called ultrasound-guided funicular block, allows orchiectomy to be performed under deep sedation without general anaesthesia.

Unilateral mastectomy is a common surgical procedure in feline species and requires postoperative pain management. Our study aimed to evaluate the analgesic efficacy of subarachnoid anaesthesia combined with an intercostal nerve block, in comparison with the use of sufentanyl citrate administered as a constant-rate infusion (CRI). Twenty cats were randomly divided into two groups (n = 10/group) based on the analgesic protocol used: the first received loco-regional anaesthesia with levobupivacaine (LR group), and the second received a CRI of sufentanyl (SUF group). The evaluation criteria during surgery were the need for a bolus of fentanyl in the event of an increased heart rate or increased blood pressure. In the postoperative period, the levels of comfort/discomfort and pain were used to obtain a score according to the UNESP-Botucatu multimodal scale. Subjects who scored above seven received analgesic drug supplementation. Intraoperative analgesia was satisfactory, with good haemodynamic stability in both groups. Four patients in the LR group required an extra dose of methadone after they achieved the sternal decubitus position, whereas those in the SUF group required many more doses. The analgesia achieved in the LR group was more satisfactory than that in the SUF group.

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Objectives The purpose of the present study was to evaluate the postoperative analgesic efficacy of fentanyl patches versus subcutaneous tramadol after canine ovariectomy, with and without unilateral mastectomy. Materials and methods A total of 40 female dogs were included in the present study, all of which were domesticated, healthy and 4–12 years of age. The animals were divided into four groups (n = 10 per group) based on the surgery and the analgesic protocol used: the TO group only underwent ovariectomy, and received postoperative tramadol; the TM group underwent both ovariectomy and mastectomy, and received postoperative tramadol; the FO group only underwent ovariectomy, and received fentanyl patches; and the FM group underwent both ovariectomy and mastectomy, and received fentanyl patches. Postoperative pain was evaluated every 4 h for 24 h using a numeric analogue scale (NAS) and a modified Glasgow Composite Measure Pain Scale Short Form (CMPS‐SF). Results The results of the present study showed that patients in all four groups tolerated postoperative surgical stress well. Analysis of variance for repeated measures did not show significant differences in the NAS scores and in Glasgow CMPS‐SF between groups in terms of pain scores or rescue analgesia. Clinical significance These results indicated that the analgesic effect of the fentanyl patch was similar to that of subcutaneous (SC) tramadol in female dogs after ovariectomy, with and without unilateral mastectomy, suggesting that the fentanyl patch may represent a valid supplementary tool for the control of postoperative pain in animals after surgery.