Role of aerobic physical training on cardiac autonomic and morphophysiological dysfunction in hypertensive rats subjected to ovarian hormone deprivation

Here we investigated the effects of physical training on cardiovascular autonomic control and cardiac morphofunctional parameters in spontaneously hypertensive rats (SHRs) subjected to ovarian hormone deprivation. Forty-eight 10-week-old SHRs were divided into two groups: ovariectomized (OVX, n=24) and sham (SHAM, n=24). Half of each group (n=12) was trained by swimming for 12 weeks (OVX-T and SHAM-T). Cardiac morphology and functionality were assessed using echocardiography, and autonomic parameters were assessed using double pharmacological autonomic block, baroreflex sensitivity (BRS), and analyses of heart rate variability (HRV) and blood pressure variability (BPV). Ovariectomy did not influence the cardiac autonomic tonus balance unlike physical training, which favored greater participation of the vagal autonomic tonus. Ovariectomy and aerobic physical training did not modify HRV and BRS, unlike BPV, for which both methods reduced low-frequency oscillations, suggesting a reduction in sympathetic vascular modulation. Untrained ovariectomized animals showed a reduced relative wall thickness (RWT) and increased diastolic and systolic volumes and left ventricular diameters, resulting in increased stroke volume. Trained ovariectomized animals presented reduced posterior wall thickness and RWT as well as increased final diastolic diameter, left ventricular mass, and stroke volume. Ovarian hormone deprivation in SHRs promoted morphofunctional adaptations but did not alter the evaluation of cardiac autonomic parameters. In turn, aerobic physical training contributed to a more favorable cardiac autonomic balance to the vagal autonomic component and promoted morphological adaptations but had little effect on cardiac functionality.

Prognosis of non-operative management of non-metastatic colorectal cancer in octa- and nonagenarians.

INTRODUCTION: The aim of the study was to establish the natural history of elderly patients with non-metastatic colorectal cancer who underwent non-operative management in comparison with those who underwent operative management. MATERIALS AND METHODS: A retrospective analysis of patients aged 80 years and above diagnosed with colorectal cancer between 2007 and 2015 in a tertiary care hospital in the Southwest of England was done. Patients were divided into non-operatively managed and operatively managed groups. Clinical demographics, Charlson Comorbidity Index, location of the tumour and overall survival between the two groups were compared. RESULTS: A total of 407 patients were studied; 132 were treated non-operatively and 275 operatively. The non-operative group included fewer right-sided colon cancers (28.7% vs 54.9%), but significantly more rectal cancers were managed non-operatively (43.9 vs 23.6%, respectively). The two and five year overall survival was 38.9% and 11.3% respectively in the non-operative group, significantly lower than patients in the operative group where the two and five year survival was 78.9% and 59.6% respectively (p = .0001). The median Charlson Comorbidity Index was 7.99 for the non-operative group and 7.49 in the operative group (p = 0.109). Patients treated non-operatively were deemed unfit without objective frailty assessment and only 43/132(32.6%) had formal anaesthetic assessment before being deemed unfit for surgery. CONCLUSION: The survival of octa- and nonagenarians with non-metastatic colorectal cancer managed conservatively is significantly less than counterparts managed operatively. Our present strategy of deciding and denying treatment of the elderly patient with colorectal cancer is arbitrary, highlighting the need for robust geriatric and frailty assessment.

The use of Endo-SPONGE® in rectal anastomotic leaks: a systematic review.

BACKGROUND: The aim of this study was to assess the efficacy of an endoluminal vacuum device (Endo-SPONGE®) in the treatment of rectal anastomotic leaks. METHODS: All studies looking at endoluminal vacuum therapy with Endo-SPONGE® in the treatment of rectal anastomotic leaks were included. A comprehensive search was conducted as per Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Primary outcome was defined as the rate of total anastomotic salvage, with secondary outcomes including rate of ileostomy closure, additional transrectal closures and functional outcomes RESULTS: Sixteen studies met the inclusion criteria. There was a significant publication bias (z = 3.53, p = 0.0004). Two hundred sixty-six patients were identified. The median treatment failure rate was 11.8% (range 0-44%), with random effects model of 0.17 (95% CI 0.11-0.22). There was improvement with early therapy start (OR 3.48) and negative correlation with neoadjuvant radiotherapy (OR 0.56). Fifty-one percent of all diverting stomas were closed at the end of treatment period and 12.8% of patients required an additional trans-rectal closure of the abscess cavity. CONCLUSIONS: Endo-SPONGE® seems to be a useful method of rectal anastomotic leak treatment in selected group of patients; however, the quality of available data is poor and it is impossible to draw a final conclusion. There is unexpected high rate of permanent ileostomy. There is a need for further assessment of this therapy with well-designed randomised or cohort studies.

Polymorphism of human telomeric quadruplexes with drugs: a multi-technique biophysical study.

The human telomeric G-quadruplex structural motif of DNA has come to be known as a new and stimulating target for anticancer drug discovery. Small molecules that interact with G-quadruplex structures in a selective way have gained impressive interest in recent years as they may serve as potential therapeutic agents. Here, we show how circular dichroism, UV resonance Raman and small angle X-ray scattering spectroscopies can be effectively combined to provide insights into structural and molecular aspects of the interaction between human telomeric quadruplexes and ligands. This study focuses on the ability of berberine and palmatine to bind with human telomeric quadruplexes and provides analysis of the conformational landscape visited by the relevant complexes upon thermal unfolding. With increasing temperature, both free and bound G-quadruplexes undergo melting through a multi-state process, populating different intermediate states. Despite the structural similarity of the two ligands, valuable distinctive features characterising their interaction with the G-quadruplex emerged from our multi-technique approach.

VIABILITY, IN VITRO DIFFERENTIATION AND MOLECULAR CHARACTERIZATION OF EQUINE ADIPOSE TISSUE-DERIVED MESENCHYMAL STEM CELLS CRYOPRESERVED IN SERUM AND SERUM-FREE MEDIUM.

BACKGROUND: The effect of freezing-thawing equine adipose tissue-derived mesenchymal stem cells (eATMSCs) have been poorly investigated. OBJECTIVE: This study is to test the influence of cryopreservation solution and temperature when adding the cryoprotectant for freezing eATMSCs, and to investigate the effects of cryopreservation on their stemness features. MATERIALS AND METHODS: Four freezing protocols were evaluated. Viability and proliferation ability of cryopreserved cells were investigated by MTT assay. Fresh and frozen thawed eATMSCs were compared for morphology, phenotypic characteristics (flow cytometry), and differentiation potential. RESULTS: A higher value of viable cells for samples frozen in FBS and a positive effect of CPA equilibration at low temperature in samples frozen in medium were observed. Morphology was similar for fresh and cryopreserved cells, such as CD expression and differentiation potential. CONCLUSION: eATMSCs can be safely stored for clinical use. FBS is superior to medium for freezing, but CPA equilibration at low temperature is beneficial when freezing in serum- free medium.

[Liver abscess]. / Abcès hépatiques.

Liver abscess is a rare and severe infection. Incidence increases because of aging of population, advances in liver and biliary surgery including liver transplantation, and immunodeficiency factors. Diagnosis depends mainly on imaging and needle aspiration for microbiological identification. Treatment is based on antibiotics, percutaneous or surgical drainage, and control of the primary source.

PATHOLOGIC AND IMPENDING FRACTURES: BIOLOGICAL AND CLINICAL ASPECTS.

Bone metastases from carcinomas are epidemiologically rising because of the increased survival rate of oncologic patients, related to several factors such as improvement of primary and secondary screening, advancement of medical research and technology and the better understanding of mechanisms underlying bone metastases origination from primary tumor. Skeletal Related Events (SREs) can seriously affect quality of life in patients with metastatic disease. These events include the necessity of radiotherapy or bone surgery, malignant hypercalcemia, pathologic fractures and spinal cord compression. Among the SREs, pathologic fractures are the most disabling events and represent an emergency in these delicate patients. A pathologic fracture is defined as a fracture that occurs at the level of a pre-existing bone lesion (that is often a tumor), spontaneously or as the result of low-energy trauma (1). The pre-existence of the metastatic lesion in the bone, its evaluation and the assessment of progression can make these complications predictable and preventable. Pathologic fractures imply several severe consequences, including patient immobilization (in the case of fractures involving the lower limbs), loss of autonomy, anaemia, need of blood transfusion, discontinuation of medical therapies or radiotherapy and protracted hospitalization. Secondary effects of prolonged immobilization and loss of autonomy further lengthen this list of complications in patients who are already significantly limited in their activities. In the present paper, the authors present a review on the main aspects involved in bone metastastic disease: biology, quality of life, economic impact and survival.

Desensitization with plasmapheresis and anti-Cd20 for ABO incompatible kidney transplantation from living donor: experience of a single center in Italy.

OBJECTIVE: Blood group incompatibility in kidney transplants from a living donor can be successfully overcome by using various desensitization protocols: intravenous immunoglobulin, plasmapheresis (PP), immunoadsorption, and double filtration PP. PATIENTS AND METHODS: From July 2010 to October 2013, we performed 10 ABO incompatible kidney transplantation (KT) procedures from a living donor. The desensitization protocol was based on rituximab and PP+cytomegalovirus immune globulin. All patients received induction with basiliximab, except 1 case treated with Thymoglobuline® (ATG) for the simultaneous presence of donor-specific antibody. Tacrolimus and mycophenolate mofetil were initiated at the time of desensitization and continued after the transplant. RESULTS: After a mean follow-up of 11.6±10.4 months, all patients are alive with a functioning graft. The mean serum creatinine concentration at 1 month, 3 months, 6 months, and 1 year was 1.48±0.29, 1.47±0.18, 1.47±0.27, and 1.5±0.27 mg/dl. Three episodes of acute cellular rejection occurred in 2 patients. There was only 1 case of BK virus infection, treated with reduction of immunosuppressive therapy. The protocol biopsy specimens at 1, 3, and 6 months were C4d positive in the absence of acute rejection. CONCLUSIONS: Desensitization with rituximab, PP, and anti-cytomegalovirus immune globulin allowed us to perform transplants from living donors to ABO incompatible recipients with excellent results and reduced costs.

Jaw cysts diagnosed in an Italian population over a 20-year period.

BACKGROUND: Cysts of the jaws (JCs) are an important topic of oral pathology, but few epidemiological data are present in the literature, in particular about the potential of recurrence. The aim of this study was to describe a case series of JCs from a single institution, evaluating the frequency, the site, the age distribution, and the percentage of recurrence of all types of JCs. METHODS: All JCs present in the histological records of the Section of Anatomic Pathology of the University of Bologna at Bellaria Hospital from 1992 to 2012 were retrieved. RESULTS: A total of 1136 jaws cysts were obtained, of which 1117 (98.3%) were odontogenic and 19 (1.7%) were nonodontogenic. About odontogenic cysts (OCs), the most frequent was the radicular cyst (538 cases), followed by parakeratinized keratocystic odontogenic tumor (pKOT, 193 cases) and dentigerous cyst (120 cases). Among pKOT, 21 out of 193 cases (10.89%) showed a recurrence after a mean time of 4.5 years (range, 1-12 years). During follow-up (mean 11 years, range 1-19 years), all 3 cases of botrioid cysts, 12 out of 46 cases of unicystic ameloblastoma (26.09%), 2 out of 20 cases of calcifying OCs (10%) and 2 out of 538 cases of radicular cyst (0.37%) showed a recurrence. CONCLUSION: Our study confirms that the distribution pattern of JCs in Italy is relatively similar to other studies worldwide and emphasizes the importance of recognizing the different histological types of JCs for their potential local aggressive behavior.

Isolation and in vitro characterization of bovine amniotic fluid derived stem cells at different trimesters of pregnancy.

Amniotic fluid (AF) is a source of multipotent mesenchymal stem cells (MSCs), very promising cells for tissue engineering in clinical application. The aim of this work was to isolate and characterize cells isolated from bovine AF as alternative sources of primitive multipotent stem cells in a species that could be a large-animal model for biomedical and biotechnology researches. Samples were recovered, at slaughterhouse, from 39 pregnant cows at different trimesters of pregnancy and cells were cultured in vitro. At passages (P) 3 and 7 differentiation towards chondrogenic, osteogenic and adipogenic lineages was induced. Flow cytometry analysis for CD90, CD105, CD73, CD44, CD34, CD45 and CD14 was performed, immunocytochemistry (ICC) for Oct4, SSEA4, α-SMA, Vimentin, N- and E- Cadherin and CK and qPCR analysis for OCT4, NANOG and SOX2 were carried out. The cell yield was significantly higher in the first trimester compared to the second and the third one (P < 0.05). Cells were isolated from 25/39 samples and cell population appeared heterogeneous. Two main cell types were identified in samples from all trimesters: round- (RS) and spindle-shaped (SS) cells. 17/25 samples showed both populations (mixed, MX). Both cell types showed MSC-markers and differentiation capability with some variability related to the passages. The SS-population also expressed low levels of stemness markers such as NANOG and SSEA4 but not OCT4. Bovine AF shows a heterogeneous cell population containing also MSCs, multipotent cells that represent an intermediate stage between embryonic stem cells and adult ones.

Prompt laparoscopic cholecystectomy would reduce morbidity and save hospital resources.

INTRODUCTION: Limited resources and organisational problems often result in significant waiting times for patients presenting with an indication for cholecystectomy. This study investigated the potential false economy of such practice. METHODS: Retrospective analysis of all patients on a waiting list for cholecystectomy between July 2007 and October 2010 was performed. The hospital computer document management system and patients' notes were used to collect data. RESULTS: A total of 1,021 patients were included in the study; 701 were listed from clinic and 320 were listed following an emergency admission. The median time on a waiting list before surgery was 96 days (range: 5-381 days). Eighty-seven patients (8.5%) had an emergency admission with a gallstone related problem while on a waiting list. This resulted in 488 cumulative inpatient days. There was a significant correlation between increased time spent on the waiting list and increased chance of an emergency admission (p=0.01). Patients added to the waiting list from emergency admissions were more likely to be admitted with complications than those listed from clinic (15.3% vs 5.4%, p<0.01). There was no association between age (p=0.53) or sex (p=0.23) and likelihood of emergency admission while on a waiting list. CONCLUSIONS: Prompt elective surgery and same-admission emergency laparoscopic cholecystectomy can reduce waiting list patient morbidity and is likely to save resources in the long term.

Treatment of port wine stains with pulsed dye laser and topical timolol: a multicenter randomized controlled trial.

BACKGROUND: Neoangiogenesis occurs within days following laser treatment of port wine stains (PWS), and plays a central role in treatment failures. Topical use of timolol can significantly reduce the production of vascular endothelial growth factor in vitro, and in animal models. OBJECTIVES: The aim of this study was to assess the efficacy of topical timolol in combination with pulsed dye laser (PDL) treatment, compared with PDL alone, for treating PWS. METHODS: This was a prospective multicenter controlled trial performed in children with PWS of the face who had not previously received laser treatment. After randomization, one group was treated with PDL alone, and the other with PDL followed by twice daily applications of timolol gel. Three laser sessions were performed at 1-month intervals with fixed parameters. The evaluation was performed on standardized pictures by two independent physicians blinded to the treatment received. The primary endpoint was marked or complete improvement of the PWS [Investigator Global Assessment (IGA) 3 or 4] 1 month after the third session. RESULTS: Twenty-two children were included. Two patients were lost to follow-up. There was no difference in the success rate between the two groups (IGA 3 or 4 observed in one of 10 patients and two of 12 patients, for PDL alone, and for PDL associated with topical timolol, respectively; P = 1·0). No side-effect related to the application of topical timolol was observed. CONCLUSIONS: The addition of timolol gel for preventing neoangiogenesis failed to significantly improve the efficacy of PDL treatment of PWS.

Clinical predictors of vertebral osteoporotic fractures in post-menopausal women: a cross-sectional analysis.

BACKGROUND: Osteoporosis is a very common bone disorder and accounts for 1.4 million vertebral compression fractures (VCFs) per year, mostly in post-menopausal women. AIM: The aim of this study was to develop a risk scoring system to identify and gauge the risk of osteoporotic VCFs in post-menopausal women. MATERIALS AND METHODS: We conducted a retrospective cross-sectional study on 477 post-menopausal women consecutively visited at our institution. We studied 15 different clinical variables, i.e. age, body mass index (BMI), weight, L1-L4 lumbar T-Score, L1-L4 lumbar Z-Score, L1-L4 lumbar bone mineral density (BMD), femoral neck T-Score, femoral neck Z-Score, femoral neck BMD, smoking habit, alcohol consumption, 25-OH-vitamin D, total alkaline phosphatase, bone alkaline phosphatase, and L4 vertebral volume. Study population was split in a derivation and a validation cohort. A logistic regression model was used to develop a predictive score of osteoporotic VCFs in the derivation cohort, finally the performance of the score was tested in the validation cohort. RESULTS: Age, L1-L4 lumbar T-Score, femoral neck T-Score, L4 vertebral volume, and smoking habit were found to be predictors of VCFs. To each variable a score from 0 to +12 was assigned to the magnitude of regression coefficient. A score ≥ 22 identified VCFs with a sensitivity of 87%/89% and a specificity of 87%/90% in the derivation and validation cohorts, respectively. CONCLUSIONS: Our findings indicate that a simple score derived from clinical history and routine diagnostic workout can be usefully employed to gauge the risk of fragility VCFs in post-menopausal women.

Epidemiological and clinical features of pyogenic spondylodiscitis.

Pyogenic spondylodiscitis (PS) is an uncommon but important infection, that represents 3-5% of all cases of osteomyelitis. The annual incidence in Europe has been estimated to be from 0.4 to 2.4/100,000. A has been reported, with peaks at age less than 20 years and in the group aged 50-70 years. The incidence of PS seems to be increasing in the last years as a result of the higher life expectancy of older patients with chronic debilitating diseases, the rise in the prevalence of immunosuppressed patients, intravenous drug abuse, and the increase in spinal instrumentation and surgery. PS is in most cases a hematogenous infection. Staphylococcus aureus is the most frequent causative microorganism, accounting for about one half of the cases of PS. Gram-negative rods are causative agents in 7-33% of PS cases. Coagulase-negative staphylococci (CoNS) have been reported in 5-16% of cases. Staphylococcus epidermidis is often related to post-operative infections and intracardiac device-related bacteremia. Unremitting back pain, characteristically worsening during the night, is the most common presenting symptom, followed by fever that is present in about one half of the cases. The mortality of PS ranges from 0 to 11%. In a significant number of cases, recrudescence, residual neurological defects or persistent pain may occur.