TERNARY PHASE DIAGRAM OF KETAMINE ((R,S)-2-(2-CHLOROPHENYL)-2-METHYLAMINOCYCLOHEXANONE) IN ETHANOL AND PRELIMINARY STUDIES AIMING AT ENANTIOSELECTIVE CRYSTALLIZATION OF S-KETAMINE

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Crystallization is an important industrial-scale process for the purification of enantiomers that depends on a phase diagram. In this work, the ternary phase diagram of R- and S-ketamine in ethanol was determined. The eutectic point indicated that crystallization of pure enantiomers from solutions containing more than 75% of the desired enantiomer is feasible. Solubility studies showed the feasibility of using temperature control to conduct the process. Batch crystallization of ketamine (S/R:80/20) solutions at 25 degrees C provided the isolation of S-ketamine (purity of 100%) with a yield from 65 to 70% and a productivity of 6.5 g/(1h).262427434Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)UnicampFundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq

Lineage-specific serology confirms Brazilian Atlantic forest lion tamarins, Leontopithecus chrysomelas and Leontopithecus rosalia, as reservoir hosts of Trypanosoma cruzi II (TcII).

BACKGROUND: Trypanosoma cruzi, the agent of Chagas disease in humans, has a vast reservoir of mammalian hosts in the Americas, and is classified into six genetic lineages, TcI-TcVI, with a possible seventh, TcBat. Elucidating enzootic cycles of the different lineages is important for understanding the ecology of this parasite, the emergence of new outbreaks of Chagas disease and for guiding control strategies. Direct lineage identification by genotyping is hampered by limitations of parasite isolation and culture. An indirect method is to identify lineage-specific serological reactions in infected individuals; here we describe its application with sylvatic Brazilian primates. METHODS: Synthetic peptides representing lineage-specific epitopes of the T. cruzi surface protein TSSA were used in ELISA with sera from Atlantic Forest Leontopithecus chrysomelas (golden-headed lion tamarin), L. rosalia (golden lion tamarin), Amazonian Sapajus libidinosus (black-striped capuchin) and Alouatta belzebul (red-handed howler monkey). RESULTS: The epitope common to lineages TcII, TcV and TcVI was recognised by sera from 15 of 26 L. chrysomelas and 8 of 13 L. rosalia. For 12 of these serologically identified TcII infections, the identity of the lineage infection was confirmed by genotyping T. cruzi isolates. Of the TcII/TcV/TcVI positive sera 12 of the 15 L. chrysomelas and 2 of the 8 L. rosalia also reacted with the specific epitope restricted to TcV and TcVI. Sera from one of six S. libidinous recognised the TcIV/TcIII epitopes. CONCLUSIONS: This lineage-specific serological surveillance has verified that Atlantic Forest primates are reservoir hosts of at least TcII, and probably TcV and TcVI, commonly associated with severe Chagas disease in the southern cone region of South America. With appropriate reagents, this novel methodology is readily applicable to a wide range of mammal species and reservoir host discovery

Undifferentiated connective tissue disease: a seven-center cross-sectional study of 184 patients

The purpose of this study was to characterize the clinical and serological features of a large cohort of patients with antinuclear antibody (ANA) positive undifferentiated connective tissue disease (UCTD). Consecutive patients with UCTD, followed up at the Rheumatology Clinic of the participating centers, were included. Data from these patients were obtained by clinical evaluation and chart review. All patients were diagnosed as having UCTD on basis of the following criteria: positive ANA plus at least one clinical feature of connective tissue disease, but not fulfilling classification criteria for any differentiated connective tissue disease. One hundred eighty-four patients were studied (female patients-94.5%; mean age at time of evaluation-47 years). The most prevalent manifestations were arthralgia (66%), arthritis (32%), Raynaud's phenomenon (30%), sicca symptoms (30%), and leukopenia (19%). The prevalence of ANA was 100%, anti-SSA 20%, anti-dsDNA 14%, and anti-SSB 7%. Patients with anti-dsDNA/anti-Sm, anticentromere/anti-Scl70, or anti-SSA/anti-SSB antibodies more frequently presented a set of manifestations close to systemic lupus erythematosus (SLE), systemic sclerosis, or Sjögren syndrome, respectively. We analyze a large cohort of UCTD. Seventy-two percent of these UCTD patients present lupus-, scleroderma-, or Sjögren-like features but do not fulfill classification criteria and mostly present a mild disease

Characterization of the striatal extracellular matrix in a mouse model of Parkinson’s disease

Parkinson’s disease’s etiology is unknown, although evidence suggests the involvement of oxidative modifications of intracellular components in disease pathobiology. Despite the known involvement of the extracellular matrix in physiology and disease, the influence of oxidative stress on the matrix has been neglected. The chemical modifications that might accumulate in matrix components due to their long half-live and the low amount of extracellular antioxidants could also contribute to the disease and explain ineffective cellular therapies. The enriched striatal extracellular matrix from a mouse model of Parkinson’s disease was characterized by Raman spectroscopy. We found a matrix fingerprint of increased oxalate content and oxidative modifications. To uncover the effects of these changes on brain cells, we morphologically characterized the primary microglia used to repopulate this matrix and further quantified the effects on cellular mechanical stress by an intracellular fluorescence resonance energy transfer (FRET)-mechanosensor using the U-2 OS cell line. Our data suggest changes in microglia survival and morphology, and a decrease in cytoskeletal tension in response to the modified matrix from both hemispheres of 6-hydroxydopamine (6-OHDA)-lesioned animals. Collectively, these data suggest that the extracellular matrix is modified, and underscore the need for its thorough investigation, which may reveal new ways to improve therapies or may even reveal new therapies.This research was funded by FEDER (Fundo Europeu de Desenvolvimento Regional) funds through the COMPETE 2020 Operational Program for Competitiveness and Internationalization (POCI), Portugal 2020, and Portuguese funds through FCT (ID/BIM/04293/2020), UnIC (UID/IC/00051/2019), iBiMED (UID/BIM/04501/2020 and POCI-01-0145-FEDER-007628), and LAQV/REQUIMTE (UIDB/50006/2020) research units as well as RV’s Fellowship Grant (IF/00286/2015). Ana Freitas acknowledges FCT for her PhD scholarship (SFRH/BD/111423/2015), Miguel Aroso is hired through the Scientific Employment Stimulus from FCT (CEECIND/03415/2017), and M.L. has an FCT RJEC Id 3762 contract.The authors thank Eduardo D Martín Montiel for his support, fruitful discussions, suggestions, and technical and scientific help. The authors also thank Sofia Lamas and all the i3S Animal facility personnel for their support with the animals throughout the study. Raman spectroscopy, together with wide field and confocal microscopy, were performed at the i3S Scientific Platform Bioimaging, member of the PPBI (Plataforma Portuguesa de Bioimagem, POCI-01-0145-FEDER-022122)

Saúde mental na atenção básica: prática da equipe de saúde da família

A inclusão das ações de saúde mental no contexto do Sistema Único de Saúde (SUS) contribuiu para a consolidação da Reforma Psiquiátrica Brasileira bem como demanda a reorientação da prática das equipes de saúde da família junto aos usuários com necessidades do campo da saúde mental. Este estudo tem por objetivo identificar e analisar na produção científica as ações realizadas pelos profissionais da equipe de saúde da família na atenção à saúde mental. Mediante análise sistemática emergiram os seguintes temas: visita domiciliar ao doente mental e seus familiares; vínculo e acolhimento; encaminhamento; oficinas terapêuticas. Concluiu-se que as ações de saúde mental desenvolvidas na atenção básica não apresentam uniformidade em sua execução e ficam na dependência do profissional ou da decisão política do gestor indicando que os profissionais devem apropriar-se de novas práticas para desenvolverem uma assitência integral e, portanto, há necessidade de investimentos para qualificação dos profissionais

Mode of Delivery and Asthma at School Age in 9 European Birth Cohorts

Evidence on the association between mode of delivery and asthma at school age is inconclusive. We assessed the associations between specific modes of delivery and asthma in children from 9 European birth cohorts that enrolled participants between 1996 and 2006. Cohort-specific crude and adjusted risk ratios for asthma at ages 5–9 years were calculated using Poisson regression models and pooled. A sensitivity analysis was carried out in children born at term to reduce confounding due to perinatal factors. The study included 67,613 participants. Cohortspecific rates of cesarean delivery varied from 9.4% to 37.5%. Cesarean delivery, as opposed to vaginal delivery, was associated with an increased risk of asthma (adjusted risk ratio (aRR) = 1.22, 95% confidence interval (CI): 1.02, 1.46). Compared with spontaneous vaginal delivery, the adjusted risk ratio was 1.33 (95% CI: 1.02, 1.75) for elective cesarean delivery, 1.07 (95% CI: 0.94, 1.22) for emergency cesarean delivery, and 0.97 (95% CI: 0.84, 1.12) for operative vaginal delivery. In children born at term, the associations were strengthened only for elective cesarean delivery (aRR = 1.49, 95% CI: 1.13, 1.97). The large sample size allowed analysis of the associations between specific modes of delivery and asthma at school age. The increased risk of asthma associated with elective cesarean delivery, especially among children born at term, is relevant in counteracting the increasing use of this procedure, which is often performed without a clear medical indication.This work was supported by the European Community’s Seventh Framework Programme (FP7/2009–2013) under a grant agreement (grant 241604) and by the University of Turin and the San Paolo Foundation (Turin, Italy). Data collection was funded and the study teams of all participating birth cohorts were supported by local and/or national research organizations

Testing quantum mechanics in non-Minkowski space-time with high power lasers and 4th generation light sources

A common misperception of quantum gravity is that it requires accessing energies up to the Planck scale of 1019 GeV, which is unattainable from any conceivable particle collider. Thanks to the development of ultra-high intensity optical lasers, very large accelerations can be now the reached at their focal spot, thus mimicking, by virtue of the equivalence principle, a non Minkowski space-time. Here we derive a semiclassical extension of quantum mechanics that applies to different metrics, but under the assumption of weak gravity. We use our results to show that Thomson scattering of photons by uniformly accelerated electrons predicts an observable effect depending upon acceleration and local metric. In the laboratory frame, a broadening of the Thomson scattered x ray light from a fourth generation light source can be used to detect the modification of the metric associated to electrons accelerated in the field of a high power optical laser

An analysis of risk factors for arterial hypertension in adolescent students

The objective of the study was to evaluate some risk factors for increases in systemic arterial blood pressure. This transversal study was carried out with 145 individuals from 12 to18 years of age at two state schools in the city of Pico in the state of Piauí in Brazil. The majority were female (62.8%). The median age was 14.8 years (±3.19). It was ascertained that 13 of the subjects (9.0%) were overweight [CI% 73.0-86.0]. Elevations in waist circumference were found in 31 (21.4%) and 76 (52.4%) had elevated arterial blood levels. There was no statistically-significant association between the above-cited risk factors and gender (p=0.088; 0.999; 0.204, respectively). However, 44.8% of the adolescents had at least one risk factor associated with arterial hypertension; 15.9% had two, and 2.1% had three. The study confirms the influence of the risk factors on arterial pressure values among adolescents. Being aware of these factors means that nurses can intervene with health education measures.El objetivo fue evaluar de los algunos factores de riesgo para aumento de los niveles de presión arterial sistémica. Estudio transversal con 145 personas de 12 a 18 años de dos escuelas públicas de la ciudad de Picos-PI. La mayoría eran mujeres (62,8%). La edad media fue de 14,8 años (±3.19). Se encontró 13 (9,0%) tenían exceso de peso [IC% 73,0 a 86,0]. Elevaciones de la circunferencia de cintura se encontraron en 31 (21,4%) y 76 (52,4%) con niveles elevados de presión arterial. No hubo asociación estadísticamente significativa de los factores de riesgo mencionados anteriormente investigado con el sexo (p=0,088, 0,999, 0,204, respectivamente). Sin embargo, 44,8% de los jóvenes tenían al menos un factor; 15,9% dos y 2,1% tres factores relacionados con la hipertensión. Confirma la influencia de factores de riesgo en los valores de presión arterial en la juventud. Delante del conocimiento de estos factores, la enfermería podrá intervenir con medidas de educación en salud.O objetivo do estudo foi avaliar alguns fatores de risco para aumento dos níveis de pressão arterial sistêmica. Trata-se de estudo transversal, desenvolvido com 145 indivíduos de 12 a 18 anos, de duas escolas públicas da cidade de Picos, PI. A maioria era composta por mulheres (62,8%). A média de idade foi de 14,8 anos (±3,19). Verificou-se que 13 (9,0%) apresentavam excesso de peso [IC% 73,0-86,0]. Elevações da circunferência abdominal foram encontradas em 31 (21,4%), e 76 (52,4%) tinham elevação nos níveis de pressão arterial. Não houve associação estatisticamente significante dos fatores de risco investigados citados anteriormente com o sexo (p=0,088; 0,999; 0,204, respectivamente). No entanto, 44,8% dos adolescentes tinham pelo menos um fator, 15,9% dois e 2,1%, três fatores associados indicativos de hipertensão arterial. Confirma-se a influência de fatores de risco sobre os valores da pressão arterial em adolescentes. Diante do conhecimento desses fatores, a enfermagem poderá intervir com medidas de educação em saúde

The influence of health expenditures on household impoverishment in Brazil

OBJECTIVE To analyze the variation in the proportion of households living below the poverty line in Brazil and the factors associated with their impoverishment. METHODS Income and expenditure data from the Household Budget Survey, which was conducted in Brazil between 2002-2003 (n = 48,470 households) and 2008-2009 (n = 55,970 households) with a national sample, were analyzed. Two cutoff points were used to define poverty. The first cutoff is a per capita monthly income below R$100.00 in 2002-2003 and R$140.00 in 2008-2009, as recommended by the Bolsa Família Program. The second, which is proposed by the World Bank and is adjusted for purchasing power parity, defines poverty as per capita income below US$2.34 and US$3.54 per day in 2002-2003 and 2008-2009, respectively. Logistic regression was used to identify the sociodemographic factors associated with the impoverishment of households. RESULTS After subtracting health expenditures, there was an increase in households living below the poverty line in Brazil. Using the World Bank poverty line, the increase in 2002-2003 and 2008-2009 was 2.6 percentage points (6.8%) and 2.3 percentage points (11.6%), respectively. Using the Bolsa Família Program poverty line, the increase was 1.6 (11.9%) and 1.3 (17.3%) percentage points, respectively. Expenditure on prescription drugs primarily contributed to the increase in poor households. According to the World Bank poverty line, the factors associated with impoverishment include a worse-off financial situation, a household headed by an individual with low education, the presence of children, and the absence of older adults. Using the Bolsa Família Program poverty line, the factors associated with impoverishment include a worse-off financial situation and the presence of children. CONCLUSIONS Health expenditures play an important role in the impoverishment of segments of the Brazilian population, especially among the most disadvantaged