No abstract

Parkinson's disease (PD) is most commonly a sporadic illness, and is characterized by degeneration of substantia nigra dopamine (DA) neurons and abnormal cytoplasmic aggregates of ␣-synuclein. Rarely, PD may be caused by missense mutations in ␣-synuclein. MPTP, a neurotoxin that inhibits mitochondrial complex I, is a prototype for an environmental cause of PD because it produces a pattern of DA neurodegeneration that closely resembles the neuropathology of PD. Here we show that ␣-synuclein null mice display striking resistance to MPTP-induced degeneration of DA neurons and DA release, and this resistance appears to result from an inability of the toxin to inhibit complex I. Contrary to predictions from in vitro data, this resistance is not due to abnormalities of the DA transporter, which appears to function normally in ␣-synuclein null mice. Our results suggest that some genetic and environmental factors that increase susceptibility to PD may interact with a common molecular pathway, and represent the first demonstration that normal ␣-synuclein function may be important to DA neuron viability.T he concept of genetic predisposition to disease suggests that one's genes influence susceptibility to environmental insult. However, the relationship between genetic and environmental factors is poorly understood; most models of disease focus on single genes or toxins. A major challenge of postgenomic biology will be to link the molecular pathways modified by diseaseassociated alleles to the environmental factors implicated in disease susceptibility.There is increasing evidence for genetic susceptibility to Parkinson's disease (PD) (1-3). Additionally, dysfunction of a common molecular pathway has been implicated in the familial and sporadic forms of PD. Mutations in the gene that encodes ␣-synuclein cause a rare form of dominantly inherited PD, and ␣-synuclein is an abundant protein in Lewy bodies, the proteinaceous neuronal inclusions that are the pathological hallmark of sporadic PD (4-6). The ␣-synuclein pathway is also implicated in an autosomal recessive form of PD caused by mutations in the gene encoding parkin (7,8). Epidemiological and twin studies suggest that environmental factors alter susceptibility to PD (9). The fact that exposure of humans to the environmental toxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) causes a syndrome that mimics the core neurological symptoms and relatively selective dopamine (DA) neuron degeneration of PD lends support to this concept (10, 11).We asked whether a model neurotoxin for an environmental cause of PD might act on a molecular pathway implicated in genetic and sporadic forms of the disease by generating ␣-synuclein null mice, and testing whether they display altered sensitivity to MPTP-induced degeneration of substantia nigra (SN) DA neurons. MethodsAnimal Generation. A 5.7-kb EcoRV mouse ␣-synuclein fragment (Fig. 1A) was used to generate the targeting construct. A DNA fragment containing, in order, LoxP-phosphoglycerate kinaseNeomycin-transcription blocking '...

No abstract

The data of the present study suggest no adjunctive benefit of AZM in the treatment of generalized ChP.

Among critically ill patients, dalteparin was not superior to unfractionated heparin in decreasing the incidence of proximal deep-vein thrombosis. (Funded by the Canadian Institutes of Health Research and others; PROTECT ClinicalTrials.gov number, NCT00182143.).

No abstract

S U M M A R YIntraplate seismicity has generally poor correlation with surface geological patterns. Except for major extensional features, such as aborted continental rifts, which may act as weak zones, it is usually difficult to find simple geology based models to explain differences in seismic activity in stable continental regions. Seismicity in Brazil is clearly not uniform and a few areas of higher activity have been identified. However, the seismic areas show almost no correlation with the main geological provinces, which is typical of other intraplate settings. A recent uppermantle tomography study in SE and central Brazil, using approximately 8500 P-wave and 2000 PKP-wave arrivals recorded in 59 sites since 1992, has mapped P-wave velocity anomalies from lithospheric depths down to 1300 km. In this region, higher seismic activity occurs preferentially in areas with low P-wave velocities at 150-250 km depth. The low P-wave velocities are interpreted as shallower asthenosphere. In such areas, a hotter geotherm will reduce the strength of the lithospheric upper mantle causing most of the intraplate forces to be concentrated in the brittle upper crust. The low-velocity anomalies coincide with Late Cretaceous provinces of alkaline intrusions. The proposed ponding of the Trindade plume head beneath lithospheric thin spots is consistent with our tomography results, suggesting that plume effects may have helped to preserve lithosphere/asthenosphere topography. Although other factors are also important, the present data show that stress concentrations resulting from lithosphere/asthenosphere topography should play an important role in explaining the intraplate seismicity in the Brazilian platform.

IntroductionAcute appendicitis is significantly common. Despite the increased use of computed tomography, the number of perforated cases has been stable in the past three decades. Between 2% and 6% of patients with acute appendicitis present appendiceal mass, often described as inflammatory phlegmon or abscess. Malignant tumors are confirmed by pathological analysis in 0.9–1.4% of all appendectomies performed to treat acute appendicitis. However, recent series demonstrate an elevated incidence of malignancies, ranging from 5.9 to 12%, in patients with inflammatory appendiceal mass.MethodsThe analysis was based on a systematic review of the literature. The articles were searched in PubMed for the period from 1987 to 2016. Articles presenting the incidence of the hidden malignancy among patients with appendiceal inflammatory mass were selected. Variables as age, interval appendectomy rate, the incidence of neoplasm, time to surgery, minimally invasive assessment, histology, right colectomy rate and morbidity were analyzed.ResultsA total of 13.244 patients were described as presenting acute appendicitis. Appendiceal tumor is present in approximately 1% of the appendectomies, while the rate of neoplasm varies from 10 to 29% in patients presenting appendiceal inflammatory mass. Interval appendectomies, despite been the minority of the procedures, disregard the higher morbidity associated with right sided colectomies. The review of literature also describes oncologic, histologic and clinical aspects of patients presenting appendiceal neoplasm, describing the most frequent histologic subtypes of this illness.ConclusionHidden appendiceal neoplasm in acute appendicitis are rare, fortunately. However, its incidence is much higher in patients presenting appendiceal inflammatory mass. Hence, interval appendectomy should be considered in this subgroup of patients.