Activation of acetylcholinesterase after U-74389G administration in a porcine model of intracerebral hemorrhage

Spontaneous intracerebral hemorrhage (ICH) accounts for 10–15% of all strokes. Despite high incidence, morbidity and mortality, the precise pathophysiology of spontaneous ICH is not fully understood, while there is little data concerning the mechanisms that follow the primary insult of the hematoma formation. The cholinergic system, apart from its colossal importance as a neurotransmission system, seems to also play an important role in brain injury recovery. It has been recently suggested that the brain possesses a cholinergic anti-inflammatory pathway that counteracts the inflammatory responses after ICH, thereby limiting damage to the brain itself. We, herein, report the findings of our study concerning the role of acetylcholinesterase (AChE; a crucial membrane-bound enzyme involved in cholinergic neurotransmission) in a porcine model of spontaneous ICH, with a focus on the first 4 and 24 h following the lesion’s induction, in combination with a study of the effectiveness of the lazaroid antioxidant U-74389G administration. Our study demonstrates the activation of AChE activity following U-74389G administration. The lazaroid U-74389G seems to be an established neuroprotectant and this is the first report of its supporting role in the enhancement of cholinergic response to the induction of ICH.     

Role of genetics in the diagnosis and prognosis of Crohn's disease

Considering epidemiological, genetic and immunological data, we can conclude that the inflammatory bowel diseases are heterogeneous disorders of multifactorial etiology in which hereditability and environment interact to produce the disease. It is probable that patients have a genetic predisposition for the development of the disease coupled with disturbances in immunoregulation. Several genes have been so far related to the diagnosis of Crohn's disease. Those genes are related to innate pattern recognition receptors, to epithelial barrier homeostasis and maintenance of epithelial barrier integrity, to autophagy and to lymphocyte differentiation. So far, the most strong and replicated associations with Crohn's disease have been done with NOD2, IL23R and ATG16L1 genes. Many genes have so far been implicated in prognosis of Crohn's disease and many attempts have been made to classify genetic profiles in Crohn's disease. CARD15 seems not only a susceptibility gene, but also a disease-modifier gene for Crohn's disease. Enriching our understanding on Crohn's disease genetics is important but when combining genetic data with functional data the outcome could be of major importance to clinicians.     

Prognostic value of C-reactive protein in parapneumonic effusions

Background and objective: Parapneumonic effusions (PPE) that require drainage are referred to as complicated parapneumonic effusions (CPPE). Following resolution of these effusions, residual pleural thickening (RPT) may persist. We hypothesize that the concentrations of CRP in pleural fluid (CRP_pf) and serum (CRP_ser) can be used to identify CPPE and to predict RPT. Methods: All patients with non‐purulent PPE, who were admitted to two tertiary hospitals during a 30‐month period, were enrolled in the study. Baseline CRP_pf and CRP_ser levels were compared between patients with complicated or uncomplicated PPE, as well as between patients with or without RPT of >10 mm, 6 months after discharge from hospital. Cut‐off values for identification of CPPE and prediction of RPT were determined by receiver operating characteristic curve analysis. Logistic regression analysis was performed to assess the association between CRP levels and RPT. Results: Fifty‐four patients were included in the study. Patients with CPPE (n = 23) had significantly higher levels of both CRP_pf and CRP_ser than those with uncomplicated PPE. For identification of CPPE, a CRP_pf level >78.5 mg/L and a CRP_ser level >83 mg/L gave 84% and 47% sensitivity, with 65% and 87% specificity, respectively. Classical criteria (pleural fluid pH <7.20, LDH >1000 IU/L, glucose <600 mg/L) were superior for this purpose. A combination of classical biomarkers with CRP levels using an ‘AND’ or ‘OR’ rule improved the positive and negative predictive values, respectively. CRP_ser was an independent predictor for development of RPT (adjusted OR 1.18). A CRP_ser level >150 mg/L had 91% specificity and 61% sensitivity for prediction of RPT. Conclusions: This study demonstrated the value of CRP_ser for prediction of RPT in patients with PPE. Moreover, when used in combination with classical biomarkers, CRP levels may be a useful adjunct for decision‐making in relation to treatment of patients with non‐purulent PPE.     

Thalidomide for Treatment of Bleeding Angiodysplasias during Hemodialysis

Renal transplant patients are more prone to tuberculosis infection due to the underlying intense immunosuppression, with an incidence 20–74 times higher than that in the general population. It is associated with graft dysfunction and increased mortality rates. It can be frequently pulmonary but extra-pulmonary involvement is not rare, and in the latter case, it may be misinterpreted as genital malignancies. In this case report, we discuss a renal transplant patient with pelvic pain and fever, who was later diagnosed as having abdominopelvic tuberculosis.     

Neoadjuvant Radiotherapy for Rectal Cancer: Meta-analysis of Randomized Controlled Trials

Background

Although neoadjuvant radiotherapy may improve local control of rectal cancer, its clinical value requires further evaluation as a result of potential side effects and advances in surgical technique. A meta-analysis was performed to assess effectiveness and safety of neoadjuvant radiotherapy in the management of rectal cancer.

Methods

The following databases were searched: the Cochrane Library, Biosis, Web of Science, Embase, ASCO Abstracts and WHO International Clinical Trials Registry Platform. Randomized controlled trials on the following comparisons were included: (1) neoadjuvant therapy versus surgery alone and (2) neoadjuvant chemoradiotherapy versus neoadjuvant radiotherapy.

Results

We identified 17 and 5 relevant trials that enrolled 8,568 and 2,393 patients, respectively. Neoadjuvant radiotherapy improved local control (hazard ratio 0.59; 95 % confidence interval 0.48–0.72) compared to surgery alone even after total mesorectal excision, whereas its benefit in overall survival just failed to reach statistical significance (0.93; 0.85–1.00). However, it was associated with increased perioperative mortality (1.48; 1.08–2.03), in particular if a dose of 5 Gy per fraction was administered (1.85; 1.23–2.78). Chemoradiotherapy improved local control as opposed to radiotherapy (0.53; 0.39–0.72), with no impact on perioperative outcome and long-term survival.

Conclusions

Neoadjuvant radiotherapy improves local control in patients with rectal cancer, particularly when chemoradiotherapy is administered. The question if the use of more effective chemotherapy protocols improves overall survival warrants further investigation.     

Impact of excessive occlusal load on successfully‐osseointegrated dental implants: a literature review

The aim of the present study was to review the available evidence on the response of the peri‐implant bone when subjected to excessive occlusal forces. The search strategy included papers published in English in the Medline database and the Wiley Online Library from January 1991 to December 2011. Experimental or review papers reporting the conditions of the peri‐implant bone of dental implants submitted to excessive occlusal loading in the presence of a controlled oral hygiene regime were eligible for inclusion. The knowledge regarding the response of the peri‐implant bone when the dental implant is excessively loaded is limited, and the level of evidence is poor. With animal experimental studies showing conflicting results, it is unclear whether occlusal overload might cause marginal bone loss or total loss of osseointegration to already osseointegrated dental implants when the applied load exceeds the biologically‐acceptable limit. This biological limit is also unknown. Furthermore, higher remodeling activity of the peri‐implant bone is found around implants subjected to high loading forces.     

Brain volume dynamics in multiple sclerosis. A case-control study

ABSTRACT

Objectives: In this study, we aimed to explore the extent and clinical relevance of brain volume dynamics in relapsing remitting multiple sclerosis (RRMS).

Methods: Sixty-three patients with RRMS with a disease duration of about 5 years (36 women, mean age 39.9 ± 9.4 years; mean EDSS1.4 ± 1.2, mean relapse rate 0.98 ± 1.17) and 50 healthy control individuals (24 women, mean age 39.1 ± 10.2 years) were recruited and imaged on a MRI scanner by using post-gadolinium high-resolution3D T1W sequences. Cross-sectional and longitudinal volumetric data were obtained by using SIENA(X) and FIRST software.

Results: Patients showed significantly lower subcortical volumes compared to healthy controls. Interestingly, the educational level predicted the rate of right thalamus atrophy. The mean annualized percentage of brain volume change (aPBVC) was ?0.92% (±1.64%) and was presented in higher rates during the first five years after MS diagnosis.

Conclusion: Brain atrophy mainly involved subcortical grey matter structures and was more conspicuous during the first years of MS diagnosis. The buffering role of education in atrophy was also corroborated by this study.