Dammhampton7020

Thalamic infusion of adeno-associated viral (AAV) vectors has been shown to have therapeutic effects in neuronopathic lysosomal storage diseases. Preclinical studies in sheep model of Tay-Sachs disease demonstrated that bilateral thalamic injections of AAV gene therapy are required for maximal benefit. read more Translation of thalamic injection to patients carries risks in that 1) it has never been done in humans, and 2) dosing scale-up based on brain weight from animals to humans requires injection of larger volumes. To increase the safety margin of this infusion, a flexible cannula was selected to enable simultaneous bilateral thalamic infusion in infants while monitoring by imaging and/or to enable awake infusions for injection of large volumes at low infusion rates. In this study, we tested various infusion volumes (200-800 µL) and rates (0.5-5 µL/min) to determine the maximum tolerated combination of injection parameters. Animals were followed for ~1 month post-injection with MRI performed at 14 and 28 days. T1-weighted MRI was used to quantify thalamic damage followed by histopathological assessment of the brain. Trends in data show that infusion volumes of 800 µL (2× the volume required in sheep based on thalamic size) resulted in larger lesions than lower volumes, where the long infusion times (between 13 to 26 hours) could have contributed to the generation of larger lesions. The target volume (400 µL, projected to be sufficient to cover most of the sheep thalamus) created the smallest lesion size. Cannula placement alone did result in damage, but this is likely associated with an inherent limitation of its use in a small brain due to the length of the distal rigid portion and lack of stable fixation. An injection rate of 5 µL/min at a volume approximately 1/3 of the thalamus (400µL-600µL) appears to be well tolerated in sheep both clinically and histopathologically.Objectives To investigate the occurrence of signs of altered psychomotor capacity (SAPC) associated with the violation of the dry law at the exits of nightclubs in the city of São Paulo, Brazil.Methods Data from drivers participating in the Balada com Ciência project were used. Alcohol dosages were measured with breathalyzer test. The use of other drugs was obtained by interviewees' self-report. SAPC (speech, walking, glazed eyes, and alcohol odor) were verified by the interviewers at the time of the interview and categorized as "no sign" or "at least one sign". All measurements were evaluated at the exit of the nightclubs. The population description considered the sample weighting. Logistic regression analysis evaluated the association between the occurrence of SAPC, alcohol and other drugs use, controlling for sociodemographic variables.Results At nightclubs, the SAPC among drivers are about 8 times higher when the breath alcohol concentration is above 0.05 mg/L if compared with those who did not drink alcohol, and about 30 times higher when the alcohol concentration was ≥ 0.34 mg/L in exhaled air. This finding is not generally verified in the literature for those who report the use of drugs inside nightclubs, which is interesting, since 20.4% of the interviewed population reported using drugs in the places surveyed.Conclusion This study suggests the potential of using the Perham (2007) physical test for alcohol intoxication in sobriety checkpoints at the exit of nightclubs. However, the verification of these signs is not enough for the identification of drug use by drivers.Introduction Oral nutritional supplementation (ONS) in cancer patients is justified by the low food intake caused by several factors. However, ONS can be affected by adverse events (AEs) correlated to treatment. This study aimed to compare the safety and efficacy of ONS (whey protein isolated, leucin, zinc-IMMAX®) during oncologic treatment.Methods Patients in chemo/chemoradiotherapy were randomly assigned to receive IMMAX®+nutritional counseling (NC) according to daily requirements (S arm) or NC alone (C arm) for 4 weeks. Body weight (BW), %fat-free mass (%FFM) and nutrition intake were assessed before and after. In S arm, calories from IMMAX met the energy requirements. AEs were classified according to CTC-AE-NCI.Results Eighty-five patients were included (51 females). After 4 weeks, the median of caloric intake, BW and %FFM were not statistically different in C arm. In S arm, median ONS intake was 81 g/332 kcal/day, protein intake was higher (pre 66.75 ± 31.57 g; post 88.57 ± 35.11 g; p  less then  0.01) and calories as well (pre 1,549 ± 596 kcal; post 1,756 ± 614 kcal; p = 0.02). The most common treatment related AEs were anemia, nausea/vomiting, not different between the arms. AEs supplement related were constipation and diarrhea (2 patients/4.6% each).Conclusion IMMAX was safe, well tolerated, it did not interfere with oncologic treatment and provided significant amount of protein intake in this patient population, with few related AEs.Phytochemical studies of methylene chloride soluble fraction from the 70% aqueous-alcoholic extract of Polyalthia longifolia (leaves) resulted in the isolation of two known clerodane diterpenes, namely 16α-hydroxycleroda-3,13(14)-dien-16,15-olide (1) and (4→2)-abeo-16-hydroxy-cleroda-2,13(14)-dien-15,16-olide-3-al (2). The isolated compounds were evaluated for their anti-histaminic and anti-Helicobacter pylori activities. Compound 1 was more potent than 2 with IC50 29.7 μg/mL and 189.2 μg/mL in the anti-histaminic assay and MIC equals to 31.25 μg/mL and 125 μg/mL in the anti-H. pylori assay, as compared with diclofenac (IC50 = 17.9 μg/mL) and clarithromycin (MIC = 1.95 μg/mL), respectively. The differences in their structures, as well as their activity results, indicated important characteristic features necessary for activity. It was suggested that the decalin moiety in 1 was important for both activities. On the other hand, the (4→2)-abeo migration in 2 reduced both activities. The potent activities of 1 suggest its potential application as an anti-histaminic and antimicrobial agent.This study was about a 70-year-old man with progressive dysphagia. Esophagogastroduodenoscopy showed a 1.2-cm circumferential ulcerative mass at the level of 23 cm from the upper incisors in the upper esophagus. The mass was first diagnosed as a poorly differentiated squamous cell carcinoma. McKeown esophagogastrectomy was performed with intention to treat the lesion. The pathological examination showed an esophageal neuroendocrine carcinoma that was mixed with squamous cell carcinoma component. In this report, we present a unique case of the extremely rare esophageal neoplasm, an esophageal neuroendocrine carcinoma with squamous cell carcinoma component.Objective To evaluate and compare the ability of the Guy's stone score (GSS), the S.T.O.N.E. nephrolithometry, and the Clinical Research Office of the Endourology Society (CROES) nomogram to predict the outcome of mini-percutaneous nephrolithotomy (MPNL) in children, and to identify which of the predictors involved in these scoring systems can separately affect this outcome. Patients and methods All children below 14 years who had MPNL in our center over a period of three years were included prospectively. Bivariate analyses were done to evaluate the associations of the three scoring systems and the predictors composing them with single-session stone clearance and complications. Receiver operator characteristic (ROC) curve analyses of the three scoring systems were conducted to evaluate and compare their abilities to predict the outcomes. Decision curve analyses for the three scoring systems were conducted to evaluate the clinical benefit of using each of them to predict stone clearance. Results We consecutively enrolled 92 renal units in 89 children with a median age of 9.5 years. Single-session stone clearance was achieved in 76 (82.6%) renal units. Complications occurred with 19 (20.7%) procedures. Stone multiplicity (p=0.043), staghorn stone (p=0.007), prior stone treatment (p less then 0.001), number of calyces involved (p=0.006), stone burden (p=0.003), GSS (p less then 0.001), S.T.O.N.E. nephrolithometry (p=0.012), and CROES nomogram (p less then 0.001) had significant associations with stone clearance. Only stone attenuation was significantly associated with complications (p=0.031). For prediction of stone clearance, CROES nomogram demonstrated the greatest area under the ROC curve and the greatest net benefit on decision curve analyses. Conclusions For children undergoing MPNL, CROES nomogram is the best to predict stone clearance. However, none of the studied scoring systems predicted complications efficiently.This article proposes a dynamical system modeling approach for the analysis of longitudinal data of self-regulated homeostatic systems experiencing multiple excitations. It focuses on the evolution of a signal (e.g., heart rate) before, during, and after excitations taking the system out of its equilibrium (e.g., physical effort during cardiac stress testing). Such approach can be applied to a broad range of outcomes such as physiological processes in medicine and psychosocial processes in social sciences, and it allows to extract simple characteristics of the signal studied. The model is based on a first order linear differential equation with constant coefficients defined by three main parameters corresponding to the initial equilibrium value, the dynamic characteristic time, and the reaction to the excitation. Assuming the presence of interindividual variability (random effects) on these three parameters, we propose a two-step procedure to estimate them. We then compare the results of this analysis to several other estimation procedures in a simulation study that clarifies under which conditions parameters are accurately estimated. Finally, applications of this model are illustrated using cardiology data recorded during effort tests.This study aimed to evaluate the in vitro activity of extracts of two marine sponge species, occurring in the shallows of the Yucatan peninsula coast, on two cancer and one normal mammalian cell lines. Hexane, dichloromethane, ethyl acetate and methanol extracts of Halichondria magniconulosa and Halichondria melanadocia were screened for their cytotoxic activity against hormone-dependent breast cancer (MCF-7) and human cervix cancer (SiHa) cell lines. The ethyl acetate extract of H. magniconulosa exhibited significant cytotoxicity against MCF-7 cells to a CC50 of 0.8 µg/mL, as well as high selectivity (SI = 24.5). On the other hand, SiHa cells were moderately sensitive to the dichloromethane and ethyl acetate extracts of the same species. (CC50 = 34.9 and 31.5 µg/mL, respectively). None of the extracts of H. melanadocia were considered active due their CC50's were ranged from 59.0 to 94.5 µg/mL.INTRODUCTION The pelvis rotates simultaneously around both hips along sagittal, frontal and transversal planes and its kinematics change in patients after total hip arthroplasty (THA). Consequently, it is reasonable to expect different pelvic kinematic profiles in bilateral or unilateral THA. Therefore, the aim of this study was to compare pelvic kinematics in patients with bilateral or unilateral THA. METHODS 40 patients undergoing bilateral (n = 20) or unilateral (n = 20) THA were evaluated for pelvic kinematics during standing and walking tasks using an optoelectronic system. Mean pelvic orientation was assessed during standing, whereas the Gait Variable Score (GVS), maximum and minimum peaks, range and values of pelvic tilt, obliquity and rotation during Heel-Strike and Toe-Off phases of gait cycle were calculated during walking. Data were collected the day before and at seven days after surgery. RESULTS At baseline, no between-group differences were found. At 7 days, GVS for pelvic tilt (p = 0.029) and rotation (p = 0.