Manifolds with small Dirac eigenvalues are nilmanifolds

Consider the class of n-dimensional Riemannian spin manifolds with bounded sectional curvatures and diameter, and almost non-negative scalar curvature. Let r=1 if n=2,3 and r=2^{[n/2]-1}+1 if n\geq 4. We show that if the square of the Dirac operator on such a manifold has $r$ small eigenvalues, then the manifold is diffeomorphic to a nilmanifold and has trivial spin structure. Equivalently, if M is not a nilmanifold or if M is a nilmanifold with a non-trivial spin structure, then there exists a uniform lower bound on the r-th eigenvalue of the square of the Dirac operator. If a manifold with almost nonnegative scalar curvature has one small Dirac eigenvalue, and if the volume is not too small, then we show that the metric is close to a Ricci-flat metric on M with a parallel spinor. In dimension 4 this implies that M is either a torus or a K3-surface

Glucagon-like peptide-1 receptor activation reduces ischaemic brain damage following stroke in Type 2 diabetic rats

Diabetes is a strong risk factor for premature and severe stroke. The GLP-1R (glucagon-like peptide-1 receptor) agonist Ex-4 (exendin-4) is a drug for the treatment of T2D (Type 2 diabetes) that may also have neuroprotective effects. The aim of the present study was to determine the efficacy of Ex-4 against stroke in diabetes by using a diabetic animal model, a drug administration paradigm and a dose that mimics a diabetic patient on Ex-4 therapy. Furthermore, we investigated inflammation and neurogenesis as potential cellular mechanisms underlying the Ex-4 efficacy. A total of seven 9-month-old Type 2 diabetic Goto–Kakizaki rats were treated peripherally for 4 weeks with Ex-4 at 0.1, 1 or 5 μg/kg of body weight before inducing stroke by transient middle cerebral artery occlusion and for 2–4 weeks thereafter. The severity of ischaemic damage was measured by evaluation of stroke volume and by stereological counting of neurons in the striatum and cortex. We also quantitatively evaluated stroke-induced inflammation, stem cell proliferation and neurogenesis. We show a profound anti-stroke efficacy of the clinical dose of Ex-4 in diabetic rats, an arrested microglia infiltration and an increase of stroke-induced neural stem cell proliferation and neuroblast formation, while stroke-induced neurogenesis was not affected by Ex-4. The results show a pronounced anti-stroke, neuroprotective and anti-inflammatory effect of peripheral and chronic Ex-4 treatment in middle-aged diabetic animals in a preclinical setting that has the potential to mimic the clinical treatment. Our results should provide strong impetus to further investigate GLP-1R agonists for their neuroprotective action in diabetes, and for their possible use as anti-stroke medication in non-diabetic conditions

Transcriptomic alterations in the heart of non-obese type 2 diabetic Goto-Kakizaki rats

BACKGROUND: There is a spectacular rise in the global prevalence of type 2 diabetes mellitus (T2DM) due to the worldwide obesity epidemic. However, a significant proportion of T2DM patients are non-obese and they also have an increased risk of cardiovascular diseases. As the Goto-Kakizaki (GK) rat is a well-known model of non-obese T2DM, the goal of this study was to investigate the effect of non-obese T2DM on cardiac alterations of the transcriptome in GK rats. METHODS: Fasting blood glucose, serum insulin and cholesterol levels were measured at 7, 11, and 15 weeks of age in male GK and control rats. Oral glucose tolerance test and pancreatic insulin level measurements were performed at 11 weeks of age. At week 15, total RNA was isolated from the myocardium and assayed by rat oligonucleotide microarray for 41,012 genes, and then expression of selected genes was confirmed by qRT-PCR. Gene ontology and protein-protein network analyses were performed to demonstrate potentially characteristic gene alterations and key genes in non-obese T2DM. RESULTS: Fasting blood glucose, serum insulin and cholesterol levels were significantly increased, glucose tolerance and insulin sensitivity were significantly impaired in GK rats as compared to controls. In hearts of GK rats, 204 genes showed significant up-regulation and 303 genes showed down-regulation as compared to controls according to microarray analysis. Genes with significantly altered expression in the heart due to non-obese T2DM includes functional clusters of metabolism (e.g. Cyp2e1, Akr1b10), signal transduction (e.g. Dpp4, Stat3), receptors and ion channels (e.g. Sln, Chrng), membrane and structural proteins (e.g. Tnni1, Mylk2, Col8a1, Adam33), cell growth and differentiation (e.g. Gpc3, Jund), immune response (e.g. C3, C4a), and others (e.g. Lrp8, Msln, Klkc1, Epn3). Gene ontology analysis revealed several significantly enriched functional inter-relationships between genes influenced by non-obese T2DM. Protein-protein interaction analysis demonstrated that Stat is a potential key gene influenced by non-obese T2DM. CONCLUSIONS: Non-obese T2DM alters cardiac gene expression profile. The altered genes may be involved in the development of cardiac pathologies and could be potential therapeutic targets in non-obese T2DM

Survey of culture and antibiogram in patients with impetigo

Background: Impetigo is a common infectious skin disease and most commonly occurs in children. Etiologic agents are Staphylococcus aureus or Beta-heamolytic Streptococcus group A or combination of these organisms. Adequacy of treatment is related on sensitivity of bacteria to common prescribed antibiotics.Methods: Study of the frequency of bacterial culture results from lesions and antibiograms for four systemic antibiotics cephalexin, erythromycin, cloxacillin and penicillin were assayed. Impetigo cases admitted to the dermatology clinic of Ghaem hospital in Mashhad for one year beginning from June 2001, were studied. These patients had no history of systemic or topical antimicrobial agents application. Results of antibiograms obtained from culture of skin lesions were analyzed with Chi-Square test.Findings: Twenty two (88%) patients were younger than 20 years. Twenty one cases (84%) had non bullous impetigo. In 17 (68%) cases lesions were localized on the face. Because of secondary contamination in 3 cases, statistical analysis was performed on 22 cases. The most common bacteria (95.5%) was Staphylococcus aureus. Antibiograms of S.aureus showed complete sensitivity to cephalxin in 85.3%, erythromycin in 63.6%, cloxacillin in 40.9%, and penicillin in 13.6% of cases. Conclusions: Staphylococcus aureus was the most common organism in 95.5% of cases and cephalexin was the first choice oral antibiotic followed by erythromycin

Influence of Ground Motion Duration on Responses of Concrete Gravity Dams

This study investigates the duration effect on the responses and damage of a dam–reservoir–foundation system. A group of 95 recorded accelerograms with a wide range of durations are adopted in the analyses. A novel global damage index that takes into consideration the consequences of damage at different locations on the overall dam safety is proposed. Nonlinear analysis results show that the duration is positively correlated with the accumulated damage of the dam system. An amplification coefficient that relates the response of the concrete gravity dam from short-duration and long-duration ground motions is proposed

Cystic Renal Cell Carcinoma: A Report on Outcomes of Surgery and Active Surveillance in Patients Retrospectively Identified on Pretreatment Imaging

PURPOSE We evaluated the outcomes of surgical intervention and active surveillance in patients diagnosed with cystic renal cell carcinoma at our hypothesized radiological cutoff of greater than 50% cystic. MATERIALS AND METHODS We identified all 430 patients with a pathologically confirmed cystic renal mass that fit our criteria from 2000 to 2015. The 292 patients with a lack of computerized tomography, tumors less than 50% cystic on imaging, multifocal tumors and prior renal cell carcinoma were excluded from study. Patients were stratified into benign or malignant subgroups, and radiological, clinicopathological and oncologic features were determined. Univariate and multivariate associations between clinicoradiological parameters in each group were analyzed. We similarly reviewed the records of a separate cohort of patients treated with active surveillance for cystic renal cell carcinoma. RESULTS Of the 138 identified cases of cystic renal cell carcinoma 102 (73.9%) were renal cell carcinoma and 36 (26.1%) were benign masses. Of the tumors 77.5% were Fuhrman grade 1-2, 83.4% were stage pT2 or less and 65.9% showed clear cell histology. On univariate analysis male gender, a solid component and increasing Bosniak classification were significant for malignancy. In a separate cohort we identified 38 patients on active surveillance. The growth rate was 1.0 mm per year overall and 2.3 mm per year for the solid component. At a median followup of more than 4 years in all cohorts there was no evidence of recurrence or metastasis of cystic renal cell carcinoma. CONCLUSIONS Patients with unifocal cystic renal cell carcinoma evaluated using a standardized radiological threshold of greater than 50% cystic had an excellent prognosis on active surveillance and after surgical resection