Toxic and Metabolic Myelopathies

Myelopathy describes any neurologic deficit related to the spinal cord. It is most commonly caused by its compression by neoplasms, degenerative disc disease, trauma, or infection. Less common causes of myelopathy include spinal cord tumors, infection, inflammatory, neurodegenerative, vascular, toxic, and metabolic disorders. Conditions affecting the spinal cord must be recognized as early as possible to prevent progression that may lead to permanent disability. Biopsy is rarely performed, thus the diagnosis and management rely on patient׳s history, physical examination, laboratory results, and imaging findings. Here we review the clinical presentations, pathophysiological mechanisms, and magnetic resonance imaging findings of myelopathies related to metabolic or toxic etiologies.info:eu-repo/semantics/publishedVersio

Biogas production by co-ensiling catch crops and straw, effect of substrate blend and microbial communities

The combination of catch crop (CC) and barley straw(S) for biogas production was investigated in order to evaluate the ensiling process in batch assay and in continuous process. Based on two new agriculture strategies designed to produce energy and improve nutrient cycling in organic farming are being evaluated, one of them consisting on the harvest of straw and catch crop in different periods whereas the other strategy consists on harvesting them at the same time. Catch crops is promoted to reduce nutrient leaching during rainy season and straw that is not used for animal feeding or bedding is generally left in the field. Mixtures of CC and S provides several advantages: 1) Provides adequate TS for silage, 2) Absorbs the silage effluent, 3) Produces high LAB activity, and 4) Provides an optimal C/N for anaerobic digestion (AD). The effect of feeding compositions (straw or manurea ddition) on the microbial community structures were also investigated

Opicapone as Adjunct to Levodopa Therapy in Patients With Parkinson Disease and Motor Fluctuations: A Randomized Clinical Trial

Importance: Catechol O-methyltransferase (COMT) inhibitors are an established treatment for end-of-dose motor fluctuations associated with levodopa therapy in patients with Parkinson disease (PD). Current COMT inhibitors carry a high risk for toxic effects to hepatic cells or show moderate improvement. Opicapone was designed to be effective without the adverse effects. Objective: To evaluate the efficacy and safety of 25- and 50-mg/d dosages of opicapone compared with placebo as adjunct to levodopa therapy in patients with PD experiencing end-of-dose motor fluctuations. Design: This phase 3 international, multicenter outpatient study evaluated a 25- and a 50-mg/d dosage of opicapone in a randomized, double-blind, 14- to 15-week, placebo-controlled clinical trial, followed by a 1-year open-label phase during which all patients received active treatment with opicapone. Patients with PD who experienced signs of end-of-dose deterioration and had a mean total awake off-time (state of akinesia or decreased mobility) of at least 1.5 hours, not including morning akinesia, were enrolled. Data were collected from March 18, 2011, through June 25, 2013. Data from the evaluable population were analyzed from July 31, 2013, to July 31, 2014. Main Outcomes and Measures: The primary efficacy outcome of the double-blind phase was the change from baseline in absolute off-time vs placebo based on patient diaries. The open-label phase focused on maintenance of treatment effect in off-time. Results: A total of 427 patients (258 men [60.4%] and 169 women [39.6%]; mean [SD] age, 63.1 [8.8] years) were randomized to a 25-mg/d (n = 129) or a 50-mg/d (n = 154) dosage of opicapone or to placebo (n = 144). Of these, 376 patients completed the double-blind phase and entered the open-label phase, of whom 286 completed 1 year of open-label treatment. At the end of the double-blind phase, the least squares mean change (SE) in off-time was -64.5 (14.4) minutes for the placebo group, -101.7 (14.9) minutes for the 25-mg/d opicapone group, and -118.8 (13.8) minutes for the 50-mg/d opicapone group. The adjusted treatment difference vs placebo was significant for the 50-mg/d opicapone group (treatment effect, -54.3 [95% CI, -96.2 to -12.4] minutes; P = .008), but not for the 25-mg/d opicapone group (treatment effect, -37.2 [95% CI, -80.8 to 6.4] minutes; P = .11). The off-time reduction was sustained throughout the open-label phase (-126.3 minutes at 1-year open-label end point). The most common adverse events in the opicapone vs placebo groups were dyskinesia, constipation, and dry mouth. Fifty-one patients (11.9%) discontinued from the study during the double-blind phase. Conclusions and Relevance: Treatment with a 50-mg once-daily dose of opicapone was associated with a significant reduction in mean daily off-time in levodopa-treated patients with PD and motor fluctuations, and this effect is maintained for at least 1 year. Opicapone was safe and well tolerated. Trial Registration: clinicaltrials.gov Identifier: NCT01227655

Very special relativity as relativity of dark matter: the Elko connection

In the very special relativity (VSR) proposal by Cohen and Glashow, it was pointed out that invariance under HOM(2) is both necessary and sufficient to explain the null result of the Michelson-Morely experiment. It is the quantum field theoretic demand of locality, or the requirement of P, T, CP, or CT invariance, that makes invariance under the Lorentz group a necessity. Originally it was conjectured that VSR operates at the Planck scale; we propose that the natural arena for VSR is at energies similar to the standard model, but in the dark sector. To this end we provide an ab initio spinor representation invariant under the SIM(2) avatar of VSR and construct a mass dimension one fermionic quantum field of spin one half. This field turns out to be a very close sibling of Elko and it exhibits the same striking property of intrinsic darkness with respect to the standard model fields. In the new construct, the tension between Elko and Lorentz symmetries is fully resolved. We thus entertain the possibility that the symmetries underlying the standard model matter and gauge fields are those of Lorentz, while the event space underlying the dark matter and the dark gauge fields supports the algebraic structure underlying VSR.Comment: 19 pages. Section 5 is new. Published version (modulo a footnote, and a corrected typo

Compromiso organizacional y satisfacción laboral: un estudio exploratorio en unidades de salud familiar portuguesas

Explorou-se a relação entre compromisso organizacional e satisfação laboral nos colaboradores de unidades de saúde familiar. Participaram seis unidades de saúde familiar do norte de Portugal e 105 profissionais (médico, enfermeiros e secretários clínicos). Utilizaram-se as adaptações portuguesas da Escala do Compromisso Organizacional de Meyer & Allen (1997) e do Questionário de Satisfação com o Trabalho (Spector, 1985). Os resultados sugerem associação positiva entre compromisso organizacional e satisfação laboral. Os profissionais estão moderadamente satisfeitos e comprometidos com as unidades de saúde familiar, sendo a natureza do trabalho, a relação com os colegas e a comunicação os aspectos mais satisfatórios, e as recompensas o mais insatisfatório. A componente afetiva do compromisso evidencia-se, salientando o envolvimento e a identificação dos profissionais com o projeto unidades de saúde familiar. O modelo de regressão linear revelou-se significativo, o compromisso organizacional explica 22,7% da variância da satisfação com o trabalho. Para esta amostra, o compromisso organizacional prediz a satisfação com o trabalho.This study explored the relationship between organizational commitment and job satisfaction among workers in family health units. Six family health units in the North of Portugal participated, including 105 health professionals (physicians, nurses, and clinical secretaries). The study used the Portuguese adaptations of the Organizational Commitment Scale by Meyer & Allen (1997) and the Job Satisfaction Survey (Spector, 1985). The results suggest a positive association between organizational commitment and job satisfaction. The professionals are moderately satisfied and committed to the family health units; the most satisfactory aspects are the nature of the work, relationship to coworkers, and communication, while pay is the most unsatisfactory. The affective component of the commitment appears, highlighting the professionals' involvement in (and identification with) the family health units project. The linear regression model proved significant, and organizational commitment explains 22.7% of the variance in job satisfaction. For this sample, organizational commitment predicts job satisfaction.Instituto Nacional de Saúde Dr Ricardo Jorgeinfo:eu-repo/semantics/publishedVersio

Comparative genomics of prevaccination and modern Bordetella pertussis strains

Contains fulltext : 89571.pdf (publisher's version ) (Open Access)BACKGROUND: Despite vaccination since the 1950s, pertussis has persisted and resurged. It remains a major cause of infant death worldwide and is the most prevalent vaccine-preventable disease in developed countries. The resurgence of pertussis has been associated with the expansion of Bordetella pertussis strains with a novel allele for the pertussis toxin (Ptx) promoter, ptxP3, which have replaced resident ptxP1 strains. Compared to ptxP1 strains, ptxP3 produce more Ptx resulting in increased virulence and immune suppression. To elucidate how B. pertussis has adapted to vaccination, we compared genome sequences of two ptxP3 strains with four strains isolated before and after the introduction vaccination. RESULTS: The distribution of SNPs in regions involved in transcription and translation suggested that changes in gene regulation play an important role in adaptation. No evidence was found for acquisition of novel genes. Modern strains differed significantly from prevaccination strains, both phylogenetically and with respect to particular alleles. The ptxP3 strains were found to have diverged recently from modern ptxP1 strains. Differences between ptxP3 and modern ptxP1 strains included SNPs in a number of pathogenicity-associated genes. Further, both gene inactivation and reactivation was observed in ptxP3 strains relative to modern ptxP1 strains. CONCLUSIONS: Our work suggests that B. pertussis adapted by successive accumulation of SNPs and by gene (in)activation. In particular changes in gene regulation may have played a role in adaptation

Identification of a Novel Response Regulator, Crr1, That Is Required for Hydrogen Peroxide Resistance in Candida albicans

Candida albicans colonises numerous niches within humans and thus its success as a pathogen is dependent on its ability to adapt to diverse growth environments within the host. Two component signal transduction is a common mechanism by which bacteria respond to environmental stimuli and, although less common, two component-related pathways have also been characterised in fungi. Here we report the identification and characterisation of a novel two component response regulator protein in C. albicans which we have named CRR1 (Candida Response Regulator 1). Crr1 contains a receiver domain characteristic of response regulator proteins, including the conserved aspartate that receives phosphate from an upstream histidine kinase. Significantly, orthologues of CRR1 are present only in fungi belonging to the Candida CTG clade. Deletion of the C. albicans CRR1 gene, or mutation of the predicted phospho-aspartate, causes increased sensitivity of cells to the oxidising agent hydrogen peroxide. Crr1 is present in both the cytoplasm and nucleus, and this localisation is unaffected by oxidative stress or mutation of the predicted phospho-aspartate. Furthermore, unlike the Ssk1 response regulator, Crr1 is not required for the hydrogen peroxide-induced activation of the Hog1 stress-activated protein kinase pathway, or for the virulence of C. albicans in a mouse model of systemic disease. Taken together, our data suggest that Crr1, a novel response regulator restricted to the Candida CTG clade, regulates the response of C. albicans cells to hydrogen peroxide in a Hog1-independent manner that requires the function of the conserved phospho-aspartate