Effect of soya phosphatidylcholine and possible underlying mechanism on ischemia/reperfusion injury in isolated perfused rat heart: an experimental and computational study.

This study was designed to assess the effect of soya phosphatidylcholine (SPC) against ischemia/reperfusion (I/R) injury and the possible underlying mechanism using experimental and computational studies. I/R injury was induced by global ischemia for 30 min followed by reperfusion for 120 min. The perfusion of the SPC was performed for 10 min before inducing global ischemia. In the mechanistic study, the involvement of specific cellular pathways was identified using various inhibitors such as ATP-dependent potassium channel (KATP) inhibitor (glibenclamide), protein kinase C (PKC) inhibitor (chelerythrine), non-selective nitric oxide synthase inhibitor (L-NAME), and endothelium remover (Triton X-100). The computational study of various ligands was performed on toll-like receptor 4 (TLR4) protein using AutoDock version 4.0. SPC (100 µM) significantly decreased the levels of cardiac damage markers and %infarction compared with the vehicle control (VC). Furthermore, cardiodynamics (indices of left ventricular contraction (dp/dtmax), indices of left ventricular relaxation (dp/dtmin), coronary flow, and antioxidant enzyme levels were significantly improved as compared with VC. This protective effect was attenuated by glibenclamide, chelerythrine, and Triton X-100, but it was not attenuated by L-NAME. The computational study showed a significant bonding affinity of SPC to the TLR4-MD2 complex. Thus, SPC reduced myocardial I/R injury in isolated perfused rat hearts, which might be governed by the KATP channel, PKC, endothelium response, and TLR4-MyD88 signaling pathway.

How the Abstract Becomes Concrete: Irrational Numbers Are Understood Relative to Natural Numbers and Perfect Squares.

Mathematical cognition research has largely emphasized concepts that can be directly perceived or grounded in visuospatial referents. These include concrete number systems like natural numbers, integers, and rational numbers. Here, we investigate how a more abstract number system, the irrationals denoted by radical expressions like 2, is understood across three tasks. Performance on a magnitude comparison task suggests that people interpret irrational numbers (specifically, the radicands of radical expressions) as natural numbers. Strategy self-reports during a number line estimation task reveal that the spatial locations of irrationals are determined by referencing neighboring perfect squares. Finally, perfect squares facilitate the evaluation of arithmetic expressions. These converging results align with a constellation of related phenomena spanning tasks and number systems of varying complexity. Accordingly, we propose that the task-specific recruitment of more concrete representations to make sense of more abstract concepts (referential processing) is an important mechanism for teaching and learning mathematics.

Myelophthisic Anemia in a Patient with Lobular Breast Carcinoma Metastasized to the Bone Marrow.

Breast tumors have a predilection for metastasizing to the bone leading to cells being displaced by the cancer cells subsequently producing immature leukocytes and erythrocytes in the peripheral blood. We present a case of a 57-year-old female who was found to have myelophthisic anemia secondary to stage four lobular breast carcinoma metastasized to the bone marrow after being misdiagnosed as having thrombotic thrombocytopenia purpura. Diagnosis of myelophthisic anemia requires a thorough workup and treatment is based upon secondary management of the malignancy.

Cognitive control deficits during mecamylamine-precipitated withdrawal in mice: Possible links to frontostriatal BDNF imbalance.

Nicotine is a major psychoactive and addictive component of tobacco. Although cessation of tobacco use produces various somatic and affective symptoms, withdrawal-related cognitive deficits are considered to be a critical symptom that predict relapse. Therefore, delineating the cognitive mechanisms of nicotine withdrawal may likely provide gainful insights into the neurobiology of nicotine addiction. The present study was designed to examine the effects of nicotine withdrawal induced by mecamylamine, a non-specific nicotinic receptor (nAChR) antagonist, on cognitive control processes in mice using an operant strategy switching task. Brain-derived neurotrophic factor (BDNF) modulates synaptic transmission in frontostriatal circuits, and these circuits are critical for executive functions. Thus, we examined the effects of mecamylamine-precipitated nicotine withdrawal on prefrontal and striatal BDNF protein expression. Mice undergoing precipitated nicotine withdrawal required more trials to attain strategy switching criterion as compared to the controls. Error analysis indicated that impaired performance in these animals was mostly related to their inability to execute the new strategy. The striatal/prefrontal BDNF ratios robustly increased following precipitated nicotine withdrawal. Moreover, higher BDNF ratios were associated with longer task acquisition. Collectively, our findings illustrate that mecamylamine-induced nicotine withdrawal disrupts cognitive control processes and that these changes are possibly linked to perturbations in frontostriatal BDNF signaling.

Prevalence of organic disease at colonoscopy in patients with symptoms compatible with irritable bowel syndrome: cross-sectional survey.

OBJECTIVE: Guidelines for the management of irritable bowel syndrome (IBS) encourage a positive diagnosis, but some evidence suggests organic disease may be missed unless investigations are performed. We examined yield of colonoscopy in a cohort of secondary care patients meeting criteria for IBS. MATERIALS AND METHODS: Demographic data, symptoms and findings at colonoscopy were recorded prospectively in consecutive, unselected adults with gastrointestinal (GI) symptoms compatible with IBS according to the Rome III criteria. Prevalence of organic GI disease was compared between those meeting criteria for IBS, according to the presence or absence of co-existent alarm features, and by IBS subtype. RESULTS: A total of 559 patients met Rome III criteria for IBS, of whom 423 reported ≥1 alarm feature and 136 none. There was a significantly higher prevalence of organic GI disease among those reporting alarm features (117 [27.7%]), compared with those without (21 [15.4%]) (p = 0.002). In the latter group of 136 patients, Crohn's disease was the commonest finding (10 [7.4%] subjects), followed by coeliac disease (4 [2.9%] subjects), and microscopic colitis (3 [2.2%] subjects). Regardless of presence or absence of alarm features, patients with constipation-predominant IBS were less likely to exhibit organic GI disease than those with diarrhea-predominant or mixed IBS (12.7% vs. 32.1% and 23.8%, p = 0.006). CONCLUSIONS: One in six patients with symptoms compatible with IBS without alarm features in this selected group exhibited organic GI disease following investigation. Assessment of alarm features in a comprehensive history is vital to reduce diagnostic uncertainty that can surround IBS.

Effect of smoking on kidney transplant outcomes: analysis of the United States Renal Data System.

BACKGROUND: We investigated the effect of smoking on postkidney transplant outcomes in the United States Renal Data System. METHODS: In a retrospective cohort of 41,705 adult Medicare primary renal transplant recipients in the United States Renal Data System database transplanted from January 1, 2000, to June 30, 2006, and followed through October 31, 2006, we assessed Medicare claims for smoking. The association between renal allograft loss and death and smoking as a time-dependent variable was assessed with Cox nonproportional hazards regression. RESULTS: Of 41,705 Medicare primary adult renal transplant patients, there were 9.9% patients who had evidence of prior smoking and 4.6% patients with new claims for smoking after transplant. Incident smoking (new onset smokers) occurred at a mean of 1.29±0.88 years after transplant. In the adjusted analysis, factors associated with new smoking included male gender, history of drug or alcohol use, history of chronic obstructive pulmonary disease, and later year of transplant. Compared with never smokers, incident smoking after transplant was associated with increased risk of death-censored allograft loss (adjusted hazard ratio [AHR] 1.46 [95% confidence interval {CI}: 1.19-1.79]; P<0.001) and death (AHR 2.32 [95% CI: 1.98-2.72]; P<0.001). In a sensitivity analysis excluding patients with history of chronic obstructive pulmonary disease, similar results were obtained with increased risk of death-censored allograft loss (AHR 1.43 [95% CI: 1.16-1.76]; P=0.001) and death (AHR 2.26 [95% CI: 1.91-2.66]; P<0.001). DISCUSSION: Incident smoking was detrimental to graft and patient survival. Transplant programs should screen those at risk during transplant follow-up and have smoking cessation programs.

Poor outcomes associated with neutropenia after kidney transplantation: analysis of United States Renal Data System.

BACKGROUND: Posttransplant neutropenia (PTN) is relatively common after kidney transplantation, and may result in a reduction of immunosuppression, which may precipitate acute rejection. Granulocyte colony-stimulating factors (GCSF) have been used to treat PTN, although outcomes associated with use of this medication in this population are unknown. METHODS: In a retrospective cohort of 41,705 adult Medicare primary patients transplanted from January 2001 to June 2006, we assessed Medicare claims for neutropenia, leukopenia, and GCSF use, respectively. Outcomes included allograft loss and death. RESULTS: There were 6043 (14.5%) patients with claims for PTN. Factors associated with PTN included female gender, Caucasian ethnicity, ischemic heart disease, donor cytomegalovirus positive, deceased donor, expanded donor criteria, delayed graft function, elevated panel reactive antibody, higher human leukocyte antigen mismatch, and later year of transplant. Thymoglobulin induction, tacrolimus, and mycophenolate mofetil were also associated. PTN was less frequent among patients with congestive heart failure, recipient cytomegalovirus positive, and interleukin-2 induction. PTN was associated with increased risk of allograft loss (adjusted hazard ratio, 1.59; 95% confidence interval, 1.43-1.76; P<0.001) and death (adjusted hazard ratio, 1.74; 95% confidence interval, 1.59-1.90; P<0.001). Of the 6043 patients with PTN, 740 (12.2%) received GCSF. Patients who received GCSF had a lower risk of death on unadjusted analysis, but this only trended towards significance after adjustment. CONCLUSIONS: Neutropenia after renal transplantation is common and is associated with an increased risk of allograft loss and death. GCSF was used in 12% of cases and did not increase risk of allograft loss. Strategies to avoid PTN and greater use of GCSF may be indicated to prevent graft loss and death.

Transcerebellar stereotactic biopsy for brainstem lesions in children.

Brain stem lesions are pathologically heterogeneous. Pre-operative radiological diagnoses prove to be wrong in 10 to 20% of cases. It is therefore imperative to have a tissue diagnosis for appropriate therapeutic measures. We report a series of 24 patients (14 males, ten females, age range: 6-17 years) CT guided stereotactic biopsy for brain stem lesions approached via the suboccipital transcerebellar route in semi sitting position with principle used to violate only one pial plane with the biopsy probe not entering the ventral surface of the cerebellum. The inclusion and exclusion criteria with detailed material and method are discussed. Histological diagnosis was established in 23 patients (96%) with no procedure-related mortality. Our results indicate that stereotaxic approach to brain-stem lesions provides a high yield of positive histological diagnoses with a low incidence of morbidity. Awake CT-guided stereotactic biopsy via the suboccipital transcerebellar route in a semi-sitting position is a safe, reliable, and effective method for brainstem lesions that can obtain adequate tissue for histological diagnosis, thus providing each patient with the best available treatment.