Photooxidation of 2-(tert-Butyl)-3-Methyl-2,3,5,6,7,8-Hexahydroquinazolin-4(1H)-one, an Example of Singlet Oxygen ene Reaction.

Singlet oxygen ene reactions produce 2-(tert-butyl)-4a-hydroperoxy-3-methyl-2,4a, 5,6,7,8-hexahydroquinazolin-4(3H)-one quantitatively during diffusion crystallization of 2-(tert-butyl)-3-methyl-2,3,5,6,7,8-hexahydroquinazolin-4(1H)-one in n-hexane/CH2Cl2 solvent mixture. To confirm this photo-oxidation, a 1H-NMR study in CDCl3 was performed with exposure to ambient conditions (light and oxygen), with neither additional reactants nor catalysts. A theoretical study at the B3LyP/6311++G** level using the QST2 method of locating transition states suggests a two-step mechanism where the intermediate, which unexpectedly did not come from the peroxide intermediate, has a low activation energy.

Insights About the Neuroplasticity State on the Effect of Intramuscular Electrical Stimulation in Pain and Disability Associated With Chronic Myofascial Pain Syndrome (MPS): A Double-Blind, Randomized, Sham-Controlled Trial.

Background: There is limited evidence concerning the effect of intramuscular electrical stimulation (EIMS) on the neural mechanisms of pain and disability associated with chronic Myofascial Pain Syndrome (MPS). Objectives: To provide new insights into the EIMS long-term effect on pain and disability related to chronic MPS (primary outcomes). To assess if the neuroplasticity state at baseline could predict the long-term impact of EIMS on disability due to MPS we examined the relationship between the serum brain-derived-neurotrophic-factor (BDNF) and by motor evoked potential (MEP). Also, we evaluated if the EIMS could improve the descending pain modulatory system (DPMS) and the cortical excitability measured by transcranial magnetic stimulation (TMS) parameters. Methods: We included 24 right-handed female with chronic MPS, 19-65 years old. They were randomically allocated to receive ten sessions of EIMS, 2 Hz at the cervical paraspinal region or a sham intervention (n = 12). Results: A mixed model analysis of variance revealed that EIMS decreased daily pain scores by -73.02% [95% confidence interval (CI) = -95.28 to -52.30] and disability due to pain -43.19 (95%CI, -57.23 to -29.39) at 3 months of follow up. The relative risk for using analgesics was 2.95 (95% CI, 1.36 to 6.30) in the sham group. In the EIMS and sham, the change on the Numerical Pain Scale (NPS0-10) throughout CPM-task was -2.04 (0.79) vs. -0.94 (1.18), respectively, (P = 0.01). EIMS reduced the MEP -28.79 (-53.44 to -4.15), while improved DPMS and intracortical inhibition. The MEP amplitude before treatment [(Beta = -0.61, (-0.58 to -0.26)] and a more significant change from pre- to post-treatment on serum BDNF) (Beta = 0.67; CI95% = 0.07 to 1.26) were predictors to EIMS effect on pain and disability due to pain. Conclusion: These findings suggest that a bottom-up effect induced by the EIMS reduced the analgesic use, improved pain, and disability due to chronic MPS. This effect might be mediated by an enhancing of corticospinal inhibition as seen by an increase in IC and a decrease in MEP amplitude. Likewise, the MEP amplitude before treatment and the changes induced by the EIMS in the serum BDNF predicted it's long-term clinical impact on pain and disability due MPS. The trial is recorded in ClinicalTrials.gov: NCT02381171.

Neuro-Otological and Peripheral Nerve Involvement in Fabry Disease.

Fabry disease (FD) is an X-linked lysosomal storage disease, with multisystemic glycosphingolipids deposits. Neuro-otological involvement leading to hearing loss and vestibular dysfunctions has been described, but there is limited information about the frequency, site of lesion, or the relationship with peripheral neuropathy. The aim was to evaluate the presence of auditory and vestibular symptoms, and assess neurophysiological involvement of the VIII cranial nerve, correlating these findings with clinical and neurophysiological features of peripheral neuropathy. We studied 36 patients with FD with a complete neurological and neuro-otological evaluation including nerve conduction studies, quantitative sensory testing (to evaluate small fiber by warm and cold threshold detection and cold and heat pain), vestibular evoked myogenic potentials, videonistagmography, audiometry and brainstem auditory evoked potentials. Neuro-otologic symptoms included hearing loss (22.2%), vertigo (27.8%) or both (25%). An involvement of either cochlear or vestibular function was identified in most patients (75%). In 70% of our patients the involvement of both cochlear and vestibular function could not be explained by a neural or vascular mechanism. Small fiber neuropathy was identified in 77.7%. There were no significant associations between neuro-otological and QST abnormalities. Neuro-otologic involvement is frequent and most likely under-recognized in patients with FD. It lacks a specific neural or vascular pattern, suggesting multi-systemic, end organ damage. Small fiber neuropathy is an earlier manifestation of FD, but there is no correlation between the development of neuropathy and neuro-otological abnormalities.

Evidence for adaptive divergence of thermal responses among Bemisia tabaci populations from tropical Colombia following a recent invasion.

There is an increasing evidence that populations of ectotherms can diverge genetically in response to different climatic conditions, both within their native range and (in the case of invasive species) in their new range. Here, we test for such divergence in invasive whitefly Bemisia tabaci populations in tropical Colombia, by considering heritable variation within and between populations in survival and fecundity under temperature stress, and by comparing population differences with patterns established from putatively neutral microsatellite markers. We detected significant differences among populations linked to mean temperature (for survival) and temperature variation (for fecundity) in local environments. A QST  - FST analysis indicated that phenotypic divergence was often larger than neutral expectations (QST  > FST ). Particularly, for survival after a sublethal heat shock, this divergence remained linked to the local mean temperature after controlling for neutral divergence. These findings point to rapid adaptation in invasive whitefly likely to contribute to its success as a pest species. Ongoing evolutionary divergence also provides challenges in predicting the likely impact of Bemisia in invaded regions.

Construção e validação de questionário simplificado para triagem de pacientes com disfunção temporomandibular (QST/DTM) / Construction and validation of a simplified questionnaire for screening of patients with temporomandibular disorders (QST / TMD)

As disfunções temporomandibulares (DTM) representam a maior causa de dor não dentária da região orofacial. Dada sua alta prevalência na população em geral e a existência de inúmeros instrumentos diagnósticos não padronizados, buscou-se elaborar e validar um questionário simples, de acessibilidade ampla e aplicação prática, com vistas a contribuir para o diagnóstico e o estudo epidemiológico das mesmas. A estratégia utilizada na montagem do instrumento foi estabelecida com base na avaliação criteriosa de questionários já existentes na literatura, validação de expertos na área de DTM, validação fatorial, de face (na primeira fase do estudo) e, frente ao padrão ouro (RDC/TMD), na segunda fase do estudo. Na primeira fase, participaram 160 indivíduos. A consistência interna resultou num Coeficiente Alfa de Cronbach de 0,752 para o questionário com sete itens; enquanto que para o questionário com cinco itens, este resultado foi de 0,694, não sendo o mesmo, considerado baixo por avaliar apenas cinco questões e ainda, em razão do tema central da pesquisa ser bastante subjetivo. A análise fatorial confirmatória apontou para uma variância total dos fatores extraídos do questionário com sete itens, de 58,2 % e do questionário com cinco itens de 70,04%. Portanto, o questionário com cinco questões, apresentou resultados estatísticos superiores ao de sete questões. Na validação frente ao padrão ouro (RDC/TMD), foram avaliados 99 indivíduos tendo sido testados os dois questionários, com sete e com cinco questões. Na estrutura com sete questões, ao se categorizar as mesmas por totais de pontos obtidos, em quatro condições, obteve-se o melhor resultado quando se considerou com DTM a faixa entre 10 e 21 pontos, sendo 85,1% positivos também no RDC/TMD, com acurácia de 90,1% e Kappa 0,817. Nesta condição, a sensibilidade encontrada foi de 95% (IC 95%, 91 a 99), especificidade de 87% (IC 95%, 81 a 93), VPP 85%, VPN 96%, LR+ 7,3 e LR- 17,4. Quando os dados foram avaliados para o questionário com cinco questões (QST/DTM), pode-se observar que o melhor ponto de corte foi quando se considerou como portadores de DTM, os indivíduos na faixa entre 7 e 15 pontos, com acurácia de 85,8% e Kappa 0,817. Nesta condição, a sensibilidade foi 88% (IC 95%, 81,6 a 94,4), especificidade 84% (IC 95%, 76,8 a 91,2), VPP 80%, VPN 90,5%, LR+ 5,5 e LR- 7,0. A simplicidade do presente questionário (QST/DTM) com apenas cinco questões, possibilita seu uso como elemento de triagem inicial na área da dor orofacial em disfunção temporomandibular, com boa compreensibilidade, confiabilidade, reprodutibilidade e possibilidade de aplicação em pesquisas epidemiológicas. Concluiu-se que o questionário aqui validado, permite sua aplicação de forma simples tanto por profissionais e pesquisadores da Odontologia como de outras áreas da saúde. (AU)

Temporomandibular disorders (TMD) represent the biggest cause of non-dental pain in the orofacial region. In reason of its high prevalence in the general population and the existence of numerous non-standardized diagnostic tools, it was sought to develop and validate a simple questionnaire, with wide accessibility and practical application, in order to contribute to the diagnosis and epidemiological study of the same. The strategy used in the assembly of the instrument was based on careful evaluation of existing questionnaires in the literature, validation of experts in the field of TMD, face and factorial validity (at the first moment of the study) and validation against the gold standard (RDC/TMD), at the second moment of the study. At the first stage, participated 160 individuals. The internal consistency resulted in a Cronbach alpha of 0,752 for the questionnaire with seven items, while for the questionnaire with five items, this result was 0,694, not being the same considered a low value since it evaluated only five questions and yet, in reason of the subjectivity of the main theme of the research. Confirmatory factor analysis indicated a total variance of the factors extracted from the questionnaire with seven items of 58,2% and for the questionnaire with five items of 70,04%. Therefore, the questionnaire with five questions presented better statistical results them the one with seven questions. In the validation against the gold standard (RDC/TMD), 99 individuals were evaluated, being tested both questionnaires, with five and seven questions. In the structure with seven issues, when categorizing them by total points earned, on four conditions, we obtained the best result when considering with TMD the range between 10 and 21 points, being 85,1% positive also in the RDC/TMD, with an accuracy of 90,1% and Kappa 0,817. In this condition, the sensitivity was 95% (CI 95%, 91 to 99), specificity of 87% (CI 95%, 81 to 93), PPV 85%, NPV 96%, LR+ 7,3 and LR- 17,4. When the data were evaluated for the questionnaire with five questions (QST/DTM), one can observe that the best cutoff point was when considered as with TMD the individuals aged between 7 and 15 points, with an accuracy of 85,8% and 0,817 Kappa. In this condition, the sensitivity was 88% (CI 95%, 81,6 to 94,4), specificity 84% (CI, 95%, 76,8 to 91,2), PPV 80%, NPV 90,5%, LR+ 5,5 and LR- 7,0. The simplicity of this questionnaire (QST/DTM) with only five issues permits its use as an initial screening in the area of orofacial pain in temporomandibular disorders, with good responsiveness, reliability, reproducibility and possibility of application in epidemiologic researches. It was concluded that the questionnaire here validated, enables its application in a simple manner by both practitioners and researchers of Dentistry as in other areas of health. (AU)