The lack of the Celf2a splicing factor converts a Duchenne genotype into a Becker phenotype

Substitutions, deletions and duplications in the dystrophin gene lead to either the severe Duchenne muscular dystrophy (DMD) or mild Becker muscular dystrophy depending on whether out-of-frame or in-frame transcripts are produced. We identified a DMD case (GSΔ44) where the correlation between genotype and phenotype is not respected, even if carrying a typical Duchenne mutation (exon 44 deletion) a Becker-like phenotype was observed. Here we report that in this patient, partial restoration of an in-frame transcript occurs by natural skipping of exon 45 and that this is due to the lack of Celf2a, a splicing factor that interacts with exon 45 in the dystrophin pre-mRNA. Several experiments are presented that demonstrate the central role of Celf2a in controlling exon 45 splicing; our data point to this factor as a potential target for the improvement of those DMD therapeutic treatments, which requires exon 45 skipping

Silodosin in the management of lower urinary tract symptoms as a result of benign prostatic hyperplasia: who are the best candidates

Summary Background As the clinical effects of the available α1-adrenoceptors (ARs) blockers are usually considered comparable for treatment in patients suffering from lower urinary tract symptoms (LUTS) secondary to prostatic enlargement, officially recognised guidelines do not make specific recommendations regarding the choice of which agent should be considered according to the patient's characteristics. Aim To analyse data supporting the use of silodosin, a highly selective once-daily dosing α1-ARs blocker, in different daily clinical practice scenarios. Materials and methods A structured literature review was performed using data retrieved from articles assessing the role of silodosin in the management of LUTS secondary to benign prostatic hyperplasia (BPH). A literature search of English language publications was performed using MEDLINE® and Web of Science from 2000 to 2012 using the terms LUTS; BPH; silodosin; α1-ARs blockers. The papers with the highest level of evidence were identified and represent the basis of the present review. Results Available data coming from basic research analyses, randomised trials and prospective studies showed that silodosin is efficacious for the initial management of patients with LUTS. Clinical developmental safety data from patients receiving silodosin with concomitant antihypertensive therapy do not indicate an increase in risk of orthostatic hypotension. In this context, a recent study demonstrated that silodosin can be safely administered to patients who are consensually assuming phosphodiesterase type 5 inhibitors. A recent randomised crossover study comparing the efficacy of silodosin and tamsulosin in patients with LUTS showed that further significant improvement was observed after switching to silodosin treatment, while worsening or little improvement was observed after switching to tamsulosin treatment. Preliminary results seem to demonstrate a potential role of silodosin in the treatment of chronic prostatitis/chronic pelvic pain syndrome and to facilitate ureteral stone passage, as well. Discussion When considering the above cited pharmacological and clinical characteristics of the drug, silodosin can be considered in the following clinical scenario: patients suffering from moderate–severe nocturia, patients with low normal blood pressure levels and patients concomitantly treated with antihypertensive medications, patients concomitantly treated with phosphodiesterase type 5 inhibitors, patients not satisfied (for efficacy or tolerability) with previous treatment with other α1-ARs blockers. Conclusion Silodosin is efficacious for the initial management of patients with LUTS. Silodosin has a good cardiovascular safety profile and can be considered an option in patients with cardiovascular co-morbidities. It seems to be especially beneficial in patients with nocturia alone or presenting with the symptomatic trial nocturia-frequency-incomplete emptying. Patients on phosphodiesterase type 5 inhibitors treatment can be safely managed with silodosin

Bronchoalveolar lavage fluid cytological findings in healthy Amiata donkeys

Background: The approach to respiratory diseases in donkeys is similar to that for horses; nevertheless, Bronchoalveolar lavage fluid (BALF) and tracheal wash cytology in this species have been described only a few times in the literature. Aim: To describe BALF cytological findings in a cohort of 24 healthy Amiata donkeys. Methods: Bronchoalveolar lavage (BAL) was carried out via standing sedation with a large animal where the BAL catheter passed blindly through the nasal passage into the trachea. Results: The total nucleated cell count of the BALF was found similar to that already described in healthy horses and donkeys. No differences in the differential count were observed according to age and sex. A decreased macrophage percentage and an increased eosinophil percentage were observed in our donkey population when compared to the existing reference range for horses. Conclusion: The reference intervals for BAL cytology in donkeys may be significantly different for those referred for horses

Guiding nipple-areola complex reconstruction.Lliterature review and proposal of a new decision-making algorithm

Background: Nipple-areola complex reconstruction (NAR) most commonly represents the finishing touch to breast reconstruction (BR). Nipple presence is particularly relevant to the patient’s psyche, beyond any shadow of doubt. Many reconstructive options have been described in time. Surgery is easy, but final result is often disappointing on the long run. Methods: The goal of this manuscript is to analyze and classify knowledge concerning NAR techniques and the factors that influence success, and then to elaborate a practical evidence-based algorithm. Out of the 3136 available articles as of August 8th, 2020, we selected 172 manuscripts that met inclusion criteria, which we subdivided into 5 main topics of discussion, being the various NAR techniques; patient factors (including patient selection, timing and ideal position); dressings; potential complications and finally, outcomes/patient satisfaction. Results: We found 92 articles describing NAR techniques, 41 addressing patient factors (out of which 17 discussed patient selection, 14 described ideal NAC location, 10 described appropriate timing), 10 comparing dressings, 7 studying NAR complications, and 22 addressing outcomes and patient satisfaction. We elaborated a comprehensive decision-making algorithm to help narrow down the choice among NAR techniques, and choose the correct strategy according to the various scenarios, and particularly the BR technique and skin envelope. Conclusions: No single NAR technique provides definitive results, which is why we believe there is no “end-all be-all solution”. NAR must be approached as a case-by-case situation. Furthermore, despite NAR being such a widely discussed topic in scientific literature, we still found a lack of clinical trials to allow for more thorough recommendations to be elaborated. Level of Evidence III: This journal requires that authors assign a level of evidence to each submission to which Evidence-Based Medicine rankings are applicable. This excludes Review Articles, Book Reviews, and manuscripts that concern Basic Science, Animal Studies, Cadaver Studies, and Experimental Studies. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/0026

Evaluation of echocardiographic parameters during increasing infusion rates of dobutamine in isofluorane-anesthetized horses.

Aim. to evaluate changes in echocardiographic parameters during increasing infusion rates of dobutamine in anesthetized horses and to compare our results with previous studies. Materials and Methods. Six Standardbred female horses were included. All the animals were anesthetized and infused with different rates of dobutamine. MAP, HR, and some echocardiographic measurements were recorded. Statistical analysis was applied. Results. At basal conditions, HR ranged was 32-42 bpm, MAP 39-63 mmHg. MAP increased significantly in a dose-dependent manner, while CPO, HR and CO increased significantly at the higher dosage. EF, LVDs and LVVols decreased significantly in a dose-dependent manner, while IVSs increased. Arrhythmias were diagnosed 5/6 horses. Discussion. The increase of MAP was in line with literature. The HR and MAP values at T0 are comparable to previous results obtained both in anesthetized and conscious horses, while after dobutamine infusion HR and MAP values are similar to those reported in anaesthetized horses. IVSs increased and LVDs decreased with the increment of dobutamine infusion rates. These findings suggest that dobutamine, even at low infusion rates, induces an enhancement in cardiac systolic function. The dose-dependent increase of IVSs and decrease of LVDs measurements are in line with those reported for dobutamine administered in conscious horses, but with lower values. The LVVols dose-dependent reduction is in line with others. The increment of CO might be due mainly to the enhanced HR than to the weak changes of SV. CPO increased from the 5 mcg/kg/min dosage in a dose-dependent manner, as reported by other

Impact of a dexmedetomidine intravenous infusion in septic dogs: preliminary study

Sepsis represents an increasing health emergency both in human and veterinary medicine Dexmedetomidine is an alpha-2 agonist drug with sedative and analgesic properties recently used critically ill patient in human ICU. The purpose of this work was to evaluate hemodynamics effects of a continuous infusion of dexmedetomidine in septic dogs

Apoptosis as a Driver of Therapy-Induced Cancer Repopulation and Acquired Cell-Resistance (CRAC): A Simple In Vitro Model of Phoenix Rising in Prostate Cancer

Apoptotic cells stimulate compensatory proliferation through the caspase-3-cPLA-2-COX-2-PGE-2-STAT3 Phoenix Rising pathway as a healing process in normal tissues. Phoenix Rising is however usurped in cancer, potentially nullifying pro-apoptotic therapies. Cytotoxic therapies also promote cancer cell plasticity through epigenetic reprogramming, leading to epithelial-to-mesenchymal-transition (EMT), chemo-resistance and tumor progression. We explored the rela-tionship between such scenarios, setting-up an innovative, straightforward one-pot in vitro model of therapy-induced prostate cancer repopulation. Cancer (castration-resistant PC3 and androgen-sensitive LNCaP), or normal (RWPE-1) prostate cells, are treated with etoposide and left recovering for 18 days. After a robust apoptotic phase, PC3 setup a coordinate tissue-like response, repopulating and acquiring EMT and chemo-resistance; repopulation occurs via Phoenix Rising, being dependent on high PGE-2 levels achieved through caspase-3-promoted signaling; epigenetic inhibitors interrupt Phoenix Rising after PGE-2, preventing repopulation. Instead, RWPE-1 repopulate via Phoenix Rising without reprogramming, EMT or chemo-resistance, indicating that only cancer cells require reprogramming to complete Phoenix Rising. Intriguingly, LNCaP stop Phoenix-Rising after PGE-2, failing repopulating, suggesting that the propensity to engage/complete Phoenix Rising may influence the outcome of pro-apoptotic therapies. Concluding, we established a reliable system where to study prostate cancer repopulation, showing that epigenetic reprogramming assists Phoenix Rising to promote post-therapy cancer repopulation and acquired cell-resistance (CRAC)

Errors in neuroradiology

Approximately 4 % of radiologic interpretation in daily practice contains errors and discrepancies that should occur in 2-20 % of reports. Fortunately, most of them are minor degree errors, or if serious, are found and corrected with sufficient promptness; obviously, diagnostic errors become critical when misinterpretation or misidentification should significantly delay medical or surgical treatments. Errors can be summarized into four main categories: observer errors, errors in interpretation, failure to suggest the next appropriate procedure, failure to communicate in a timely and a clinically appropriate manner. Misdiagnosis/misinterpretation percentage should rise up in emergency setting and in the first moments of the learning curve, as in residency. Para-physiological and pathological pitfalls in neuroradiology include calcification and brain stones, pseudofractures, and enlargement of subarachnoid or epidural spaces, ventricular system abnormalities, vascular system abnormalities, intracranial lesions or pseudolesions, and finally neuroradiological emergencies. In order to minimize the possibility of error, it is important to be aware of various presentations of pathology, obtain clinical information, know current practice guidelines, review after interpreting a diagnostic study, suggest follow-up studies when appropriate, communicate significant abnormal findings appropriately and in a timely fashion directly with the treatment team

Evaluation of a questionnaire to detect the risk of developing ESGD or EGGD in horses

Equine gastric ulcer syndrome (EGUS) affects various categories of horses worldwide. This syndrome is now divided into two different diseases, based on the presence of lesions on either the squamous (Equine Squamous Gastric Disease, ESGD) or the glandular (Equine Glandular Gastric Disease, EGGD) mucosa. Diagnosis is based on the evaluation of the presence of gastric lesions with gastroscopic examination. As a gastroscopy can be considered expensive by clients, therapy is started often on the basis of clinical signs only. The aim of this study was to validate a questionnaire to detect the risk of developing ESGD or EGGD. The owners of 418 horses that were submitted to gastroscopic evaluation were asked to answer a questionnaire on risk factors for ESGD and EGGD. Horses were divided into three groups based on the results of the questionnaire and their risk of developing gastric lesions. In our population the survey was not useful to detect the presence and the severity of the lesions detected during gastroscopic examination, however answers to some of the questions did correlate with the development of gastric lesions. The questionnaire could therefore be a useful tool to evaluate the risk of ESGD or EGGD. Having owners periodically complete the survey could also make them more aware of changes in the conditions of the horses that could lead to gastric lesions. This could then help them seek advice from veterinarians on how to manage this potential ris