Miracle-dz/UniFAR-FTUs huggingface dataset:
Cerebellothalamocortical and pallidothalamocortical projections to the primary and supplementary motor cortical areas: A multiple tracing study in macaque monkeys

The goal of the present study was to clarify whether the primary motor cortex (Ml) and the supplementary motor cortex (SMA) both receive, via the motor thalamus, input from cerebellar and basal ganglia output nuclei. This is the first investigation that explores the problem by direct comparison, in the same animal, of thalamic zones that (1) project to M1 and SMA and (2) receive cerebellar‐nuclear (CN) and pallidal (GP) afferents. These four zones were mapped in two monkeys by means of two retrograde tracers for M1 and SMA injections and of two anterograde tracers for CN and GP injections. All injections were performed under electrophysiological control (microstimulation and multiunit recordings). Injections in cortical areas were restricted to the hand/arm representation; in the SMA, the tracer deposit was within the “SMA‐proper” (or “area F3”) and did not include its rostral extension (“pre‐SMA” or “area F6”). It was found that zones of all four types formed a number of highly complex patches of labeling that were usually not confined to one cytoarchitectonically defined thalamic nucleus. The overlap of clusters of labeled terminals and perikarya was evaluated morphometrically (area measurements) on a number of coronal sections along the anteroposterior extent of the motor thalamus. In line with previous studies, the thalamic territories innervated by CN and GP afferents rarely overlapped. However, zones projecting to M1 and/or to SMA included thalamic regions receiving CN as well as GP projections, providing the first evidence of such overlap from individual animals. The present observations support the previous conclusion from this laboratory (based on transsynaptic labeling) that the SMA receives, apart from its strong pallidal transthalamic input, a CN transthalamic input. These present findings that both M1 and SMA are recipients of transthalamic inputs from GP and CN thus support the concept that a mixed subcortical input consisting of weighted contributions from cerebellum, basal ganglia, substantia nigra, and spinothalamic tract is directed to each functional component of the sensorimotor cortex. © 1994 Wiley‐Liss, Inc.
Comparison of Goldmann Tonometry and Dynamic Contour Tonometry in Normal and Descemet Stripping Endothelial Keratoplasty Eyes

PurposeThis study aimed to compare intraocular pressures (IOP) measured by dynamic contour tonometry (DCT) with Goldmann tonometry (GAT) in Descemet stripping endothelial keratoplasty (DSEK) eyes. The agreeability between the 2 established methods and their relation to central corneal thickness (CCT) was also studied. DesignA comparative case series. MethodsForty-six eyes of DSEK were enrolled at least 3 months after the procedure. Thirty-five other eyes of the same patient cohort served as control. Intraocular pressures were measured by DCT and GAT by 2 different examiners in a randomized manner. Central corneal thickness was measured by ultrasonic pachymetry. Statistical analysis was used for the calculation of means, SD, coefficient of determination, linear regression, and Bland and Altman plot. Statistical significance was considered as P < 0.05. ResultsMean CCT was 624.49 &mgr;m and 518.41 &mgr;m in DSEK and control eyes, respectively. Mean IOP by GAT and DCT, respectively, was 19.4 and 21.5 mm Hg in DSEK eyes and 15.12 and 17.6 mm Hg in controls. Descemet stripping endothelial keratoplasty eyes showed universally higher IOP by either method in comparison with normal controls. Dynamic contour tonometry reading was significantly higher than GAT in both (P < 0.05) groups. The correlation between IOP and CCT was not significant in DSEK eyes (P > 0.05). ConclusionsA higher baseline IOP is to be expected in DSEK eyes, which is independent of corneal thickness. Both GAT and DCT can be used as a standard method to measure IOP in DSEK eyes, but their readings cannot be used interchangeably.
Promoting MΦ transepithelial migration by stimulating the epithelial cell P2Y2 receptor

In intestine, neutrophils are recruited in response to bacterial infiltration and their anti‐cellular activities contribute to inflammatory bowel diseases. In contrast, little is known regarding the recruitment of MΦ to the intestinal epithelium. Extracellular adenosine and uridine 5′‐triphosphate (ATP and UTP) can function as leukocyte chemoattractants. We investigated the effects of these nucleotides on the ability of intestinal epithelial cells (IEC) to promote MΦ transepithelial migration and adhesion. ATP and UTP promoted the migration of neutrophil‐like PLB‐985 cells and MΦ across a Caco‐2 monolayer. The MΦ‐like U‐937 cells adhered to nucleotide‐stimulated IEC monolayers. In mice with intestinal inflammation, there were infiltrating CD68+ MΦ in the colonic epithelium and CD68+ MΦ present at the apical surface of colonocytes. We determined that ATP and UTP activated the P2Y2 receptor P (P2Y2R) to increase ICAM‐1 expression, which mediated the adhesion of MΦ to the apical surface of IEC. Intriguingly, stimulation of IEC with nucleotides did not increase the adhesion of neutrophils. However, in the presence of adherent MΦ, there was adhesion of neutrophils, suggesting that MΦ may serve as anchors for neutrophil adhesion. These studies provide insight into the inflammatory mechanisms that contribute to inflammatory bowel diseases and identify potential therapeutic targets for the treatment of gastrointestinal disorders.
Cross-cultural adaptation of Jefferson scale of empathy-health professions students version: An experience with developing the Tamil translation

Background: Empathy is a key cognitive attribute among healthcare professionals that fosters better patient– healthcare provider relationships. The Jefferson scale of empathy (JSE) measures self-rated empathy among various groups of healthcare professionals–health professionals, medical students and health professions students (HPS). The authors present the experience in translating the JSE-HPS version into an Indian regional language with insights into the issues faced in every step. Methods: With official permission from the Thomas Jefferson University, the authors embarked on the translation proceeding through forward translation (three rounds of modification), back translation (two independent translates), and synthesis of a final translated version. While targeting literary accuracy, the simplicity and comprehensibility of the instrument by the study population were also ensured. Variations in regional dialects and accents across the population were considered. Results: The back-translated version was evaluated for semantic, content, cultural, and technical equivalence. It was then pretested on ten students followed by a group discussion with them to ensure the comprehensibility of the tool and the differences between written and spoken language were addressed through necessary modifications. Discussion: The Tamil translation of the HPS version of JSE is now approved by and officially available with the Thomas Jefferson University.
Patupilone-Induced Apoptosis Is Mediated by Mitochondrial Reactive Oxygen Species through Bim Relocalization to Mitochondria

Among the new microtubule-targeted agents, the epothilone family of molecules has shown promising anticancer potential, and clinical trials are currently underway for patupilone (epothilone B) in various cancer indications. In this study, we characterized novel aspects of patupilone's cellular action that may underlie its potent cytotoxicity in human neuroblastoma cells. Patupilone induced mitochondrial membrane potential collapse, mitochondrial morphological changes, and cytochrome c release, leading to apoptosis. Within the first 2 h, patupilone increased the generation of reactive oxygen species (ROS; i.e., superoxides and hydrogen peroxide, 33 ± 6 and 51 ± 3% increase, respectively), specifically from mitochondria. ROS scavengers and mitochondrial DNA depletion [ρ(-) cells] significantly protected cells against patupilone cytotoxicity, indicating that ROS generation is a key event in the initial phase of apoptosis. Although the Bim expression level was not modified by patupilone, this proapoptotic protein accumulated in the mitochondrial compartment (2.4-fold increase at IC70) after only a 6-h treatment. In contrast, Bax and Bcl-2 mitochondrial levels were not changed during treatment. It is noteworthy that ROS inhibition prevented Bim relocalization to mitochondria and mitochondrial membrane changes induced by patupilone. Altogether, our data reveal that patupilone-mediated ROS production by mitochondria initiates the intrinsic signaling cascade by inducing Bim accumulation in mitochondria. These results might explain the superior activity of patupilone in tumor cells compared with paclitaxel that is, until now, the clinical reference among microtubule-stabilizing agents. Furthermore, our data highlight the importance of mitochondria that simultaneously assume the role of activator and integrator of apoptotic signals triggered by patupilone.
Walking During the Postprandial Period Decreases Alimentary Lipaemia

Background: The magnitude and duration of the serum triacylglycerol response to a fatty meal may be predictive of coronary artery disease. Exercise can modify this aspect of cardiovascular risk but the effective intensity, duration and timing of exercise is uncertain. Methods: The influence of a single period of walking on the lipaemic response to a high-fat test meal (1.2g fat and 71 kj per kilogram body mass) was examined in 12 normolipidaemic young adults (aged 21–33 years, six men and six women). The meal was ingested on two different occasions in a balanced, crossover design. In the control phase, participants rested for 6 h after consuming the meal; in the exercise phase, they walked on a treadmill for 1.5 h at 40% of their maximal oxygen uptake, starting 1.5 h after the meal, and then rested for a further 3 h. Lipid and lipoprotein levels were measured in venous blood taken during the fasted state and at intervals for 6 h after the meal. Results: The area under the triacylglycerol–time curve was 24 ± 11 % lower during the exercise phase (P < 0.05) than during the control phase because serum triacylglycerol concentrations were lower during recovery from exercise, 3–6 h after the meal. Conclusion: Prolonged walking starting 1.5 h after the consumption of a fatty meal attenuates postprandial lipaemia in normolipidaemic young adults.
Evolution of Regulation (EU) No 540/2011 since its entry into force

Regulation (EC) No 1107/2009 concerning the placing of plant protection products (agrochemicals) entered into force in 2011. Implementing Regulation (EU) No 540/2011, in turn, manages the list of approved active substances in the European Union. This implementing regulation is divided into five parts: Part A (initial active substances dating from 2011), Part B (renewed and newly approved active substances), Part C (basic substances), Part D (low-risk active substances), and Part E (candidates for substitution) that have emerged over the years. These parts have evolved over time, with an unavoidable decline of Part A and a logical increase of the other parts. Less harmful substances for the environment have been favored by this regulation (Parts C and D); however, some candidates for substitution (Part E) will remain allowed in the coming years, despite their problematic status. This study has also examined the postponement of the final date of approval, which has resulted in one half of the active substances being affected by an extension of their approval periods.https://doi.org/10.21423/jrs-v07robin
Efficient Functional Pseudotyping of Oncoretroviral and Lentiviral Vectors by Venezuelan Equine Encephalitis Virus Envelope Proteins

ABSTRACT Murine oncoretroviruses and lentiviruses pseudotyped with envelope proteins of alphaviruses have shown great potential in providing broad-host-range, stable vectors for gene therapy. Unlike vesicular stomatitis virus G protein-pseudotyped vectors, they are not neutralized by complement and do not appear to cause significant tissue damage. Here we report the production of murine oncoretroviral and lentiviral vectors pseudotyped with the envelope proteins of Venezuelan equine encephalitis virus (VEEV). When optimized, these pseudotypes achieve titers of 106 CFU/ml, which is 5- to 10-fold higher than for previous vectors pseudotyped with envelope proteins from other alphaviruses. They can also be concentrated or stored frozen without significant loss of infectivity. Consistent with the tropism of the envelope donor, they transduce a broad array of human cell types, including lung epithelial cells, neuronal cells, lymphocytes, and fibroblasts. Infection is blocked by agents that inhibit endosomal acidification and by neutralizing antibodies against VEEV. These observations indicate that the pseudotypes present native epitopes on their surface and enter through a VEEV envelope-dependent, pH-sensitive mechanism. The fact that the pseudotypes are unaffected by sera reactive to other alphaviruses indicates that they may be useful when successive gene therapies are required in the presence of an active immune response. In this case, having an array of alphavirus-based vectors with similar cell tropisms would be highly advantageous. These vectors may also be useful in diagnostic assays in which infectious VEEV is undesirable but immune reactivity to native epitopes is required.
Results of the CONTROL trial: efficacy and safety of recombinant activated Factor VII in the management of refractory traumatic hemorrhage.

BACKGROUND Traumatic coagulopathy contributes to early death by exsanguination and late death in multiple organ failure. Recombinant Factor VIIa (rFVIIa, NovoSeven) is a procoagulant that might limit bleeding and improve trauma outcomes. METHODS We performed a phase 3 randomized clinical trial evaluating efficacy and safety of rFVIIa as an adjunct to direct hemostasis in major trauma. We studied 573 patients (481 blunt and 92 penetrating) who bled 4 to 8 red blood cell (RBC) units within 12 hours of injury and were still bleeding despite strict damage control resuscitation and operative management. Patients were assigned to rFVIIa (200 μg/kg initially; 100 μg/kg at 1 hour and 3 hours) or placebo. Intensive care unit management was standardized using evidence-based trauma "bundles" with formal oversight of compliance. Primary outcome was 30-day mortality. Predefined secondary outcomes included blood products used. Safety was assessed through 90 days. Study powering was based on prior randomized controlled trials and large trauma center databases. RESULTS Enrollment was terminated at 573 of 1502 planned patients because of unexpected low mortality prompted by futility analysis (10.8% vs. 27.5% planned/predicted) and difficulties consenting and enrolling sicker patients. Mortality was 11.0% (rFVIIa) versus 10.7% (placebo) (p = 0.93, blunt) and 18.2% (rFVIIa) versus 13.2% (placebo) (p = 0.40, penetrating). Blunt trauma rFVIIa patients received (mean ± SD) 7.8 ± 10.6 RBC units and 19.0 ± 27.1 total allogeneic units through 48 hours, and placebo patients received 9.1 ± 11.3 RBC units (p = 0.04) and 23.5 ± 28.0 total allogeneic units (p = 0.04). Thrombotic adverse events were similar across study cohorts. CONCLUSIONS rFVIIa reduced blood product use but did not affect mortality compared with placebo. Modern evidence-based trauma lowers mortality, paradoxically making outcomes studies increasingly difficult.
The Impact of Egg Limitations on Coronary Heart Disease Risk: Do the Numbers Add Up?

For over 25 years eggs have been the icon for the fat, cholesterol and caloric excesses in the American diet, and the message to limit eggs to lower heart disease risk has been widely circulated. The “dietary cholesterol equals blood cholesterol” view is a standard of dietary recommendations, yet few consider whether the evidence justifies such restrictions. Over 50 years of cholesterol-feeding studies show that dietary cholesterol does have a small effect on plasma cholesterol concentrations. The 167 cholesterol feeding studies in over 3,500 subjects in the literature indicate that a 100 mg change in dietary cholesterol changes plasma total cholesterol by 2.2 mg/dL. Today we recognize that dietary effects on plasma cholesterol must be viewed from effects on the atherogenic LDL cholesterol as well as anti-atherogenic HDL cholesterol since the ratio of LDL:HDL cholesterol is a major determinant of heart disease risk. Cholesterol feeding studies demonstrate that dietary cholesterol increases both LDL and HDL cholesterol with little change in the LDL:HDL ratio. Addition of 100 mg cholesterol per day to the diet increases total cholesterol with a 1.9 mg/dL increase in LDL cholesterol and a 0.4 mg/dL increase in HDL cholesterol. On average, the LDL:HDL ratio change per 100 mg/day change in dietary cholesterol is from 2.60 to 2.61, which would be predicted to have little effect on heart disease risk. These data help explain the epidemiological studies showing that dietary cholesterol is not related to coronary heart disease incidence or mortality across or within populations.
Experimental pain responses in children with chronic pain and in healthy children: how do they differ?

BACKGROUND Extant research comparing laboratory pain responses of children with chronic pain with healthy controls is mixed, with some studies indicating lower pain responsivity for controls and others showing no differences. Few studies have included different pain modalities or assessment protocols. OBJECTIVES To compare pain responses among 26 children (18 girls) with chronic pain and matched controls (mean age 14.8 years), to laboratory tasks involving thermal heat, pressure and cold pain. Responses to cold pain were assessed using two different protocols: an initial trial of unspecified duration and a second trial of specified duration. METHODS Four trials of pressure pain and of thermal heat pain stimuli, all of unspecified duration, were administered, as well as the two cold pain trials. Heart rate and blood pressure were assessed at baseline and after completion of the pain tasks. RESULTS Pain tolerance and pain intensity did not differ between children with chronic pain and controls for the unspecified trials. For the specified cold pressor trial, 92% of children with chronic pain completed the entire trial compared with only 61.5% of controls. Children with chronic pain exhibited a trend toward higher baseline and postsession heart rate and reported more anxiety and depression symptoms compared with control children. CONCLUSIONS Contextual factors related to the fixed trial may have exerted a greater influence on pain tolerance in children with chronic pain relative to controls. Children with chronic pain demonstrated a tendency toward increased arousal in anticipation of and following pain induction compared with controls.
Effects of the Angiotensin II Type 1 Receptor Antagonist Valsartan on the Expression of Superoxide Dismutase in Hypertensive Patients

The role of oxidative stress in the pathogenesis of vascular diseases such as hypertension has been well recognized. Angiotensin (Ang) II is regarded as a pro‐oxidant because it can stimulate the production of reactive oxygen species. The purpose of this study was to evaluate whether treatment with the Ang II type 1 (AT1) receptor antagonist valsartan has an antioxidant effect in patients with mild to moderate hypertension. A randomized, double‐blind, placebo‐controlled study was conducted in 48 stage I and II hypertensive subjects. Patients were followed every 4 weeks for 12 weeks after randomization to valsartan titrated to 80 to 160 mg once or twice daily or matching placebo. The erythrocyte superoxide dismutase (SOD) activity and expression of SOD–mRNA in polymorphonuclear leukocytes were measured before and after treatment. Valsartan showed concentration‐dependent inhibition of reactive oxygen species generation in polymorphonuclear leukocytes from hypertensive patients. The erythrocyte superoxide dismutase activity before treatment was more than 2 times higher in hypertensive subjects compared to normal controls. Superoxide dismutase activity decreased significantly after 12 weeks of treatment with valsartan but did not change with placebo. The amount of SOD‐mRNA in the polymorphonuclear leukocytes decreased progressively over 3 months in the hypertensive subjects receiving valsartan treatment but did not change in the placebo group. The production of reactive oxygen species is increased in hypertension, and superoxide dismutase activity is increased, presumably as a compensatory mechanism. Treatment with valsartan but not placebo resulted in a progressive down‐regulation of SOD‐mRNA expression and a reduction in superoxide dismutase activity, suggesting antioxidant activity and a reduction of reactive oxygen species generation. These findings imply that AT1 receptor antagonists may provide benefits to hypertensive patients beyond blood pressure reduction.
High rates of clinical and subclinical tuberculosis among HIV-infected ambulatory subjects in Tanzania.

BACKGROUND We sought to determine the prevalence of active tuberculosis among ambulatory HIV-infected persons in Tanzania with CD4 cell counts of > or =200 cells/mm3 and a bacille Calmette-Guerin vaccination scar. METHODS Subjects who volunteered for a tuberculosis booster vaccine trial were screened for active tuberculosis by obtainment of a history, physical examination, chest radiography, sputum culture and acid fast bacillus (AFB) stain, and blood culture. All subjects underwent a tuberculin skin test (TST) and lymphocyte proliferation assays (LPAs) for detection of responses to mycobacterial antigens. RESULTS Active tuberculosis was identified at baseline in 14 (15%) of the first 93 subjects who were enrolled: 10 (71%) had clinical tuberculosis (symptoms or chest radiograph findings), and 4 (29%) had subclinical tuberculosis (positive sputum AFB stain or culture results but no symptoms or chest radiograph findings). An additional 6 subjects with subclinical tuberculosis were identified subsequently. The 10 subjects with subclinical tuberculosis included 3 with positive sputum AFB stains results and 7 who were only identified by a positive sputum culture result. Compared with subjects who did not have tuberculosis, the 10 subjects with subclinical tuberculosis were more likely to have peripheral lymphadenopathy, positive TST results, and elevated LPA responses to early secreted antigenic target-6 (ESAT). Eight of 10 patients had received isoniazid because of a positive TST result before active tuberculosis was recognized. CONCLUSIONS Clinical and subclinical tuberculosis are common among ambulatory HIV-infected persons, and some cases can only be identified by sputum culture. World Health Organization guidelines for screening for latent tuberculosis before treatment do not recommend sputum culture and, therefore, may fail to identify a substantial number of HIV-infected persons with subclinical, active tuberculosis.