Miracle-dz/UniFAR-FTUs huggingface dataset:
Mechanical, Biochemical, and Electromyographic Responses to Short-Term Eccentric–Concentric Knee Extensor Training in Humans

Váczi, M, Tihanyi, J, Hortobágyi, T, Rácz, L, Csende, Z, Costa, A, and Pucsok, J. Mechanical, biochemical, and electromyographic responses to short-term eccentric–concentric knee extensor training in humans. J Strength Cond Res 25(4): 922-932, 2011-This study examined the effects of short-term eccentric-concentric knee extensor training on mechanical and biochemical variables, myoelectric activity, and muscle soreness. Seventeen men were assigned to either experimental (E, n = 10) or control group (C, n = 7). Group E performed 90 maximal isokinetic eccentric-concentric knee extensor contractions on each of 3 consecutive days (Tr1-Tr3) followed by 1-day rest, and then on 4 more consecutive days (Tr4-Tr7). Peak eccentric torque of each contraction during the training was recorded and averaged for each session (MTr). Maximal isometric torque (M0), eccentric torque (Mecc), integrated electromyography (iEMG), plasma creatine kinase (CK), and lactate dehydrogenase (LDH) activities were measured before, immediately, 24, 48, and 72 hours after Tr1, at 1 and 3 days after Tr7. Group C did not train but performed all exercise tests; CK and LDH were measured at 3 time points only. Acutely, M0 and Mecc decreased and CK, LDH, and soreness increased more in E than in C 24 hours after Tr1. Chronically, MTr and M0 increased more in E than C by Tr7 and CK, LDH, and muscle soreness gradually decreased by Tr7 whereas iEMG increased more in E than in C after Tr3 through Tr7. High-intensity short-term eccentric-concentric knee extensor exercise training produced immediate reductions in maximal voluntary force. Most likely neural adaptations contributed to rapid recovery and strength adaptations because maximal voluntary force increased by the end of the training protocol in previously trained healthy adults.
Remarkable in vitro and in vivo activities of the hydroxynaphthoquinone 566C80 against tachyzoites and tissue cysts of Toxoplasma gondii

Compound 566C80, 2-[trans-4-(4-chlorophenyl)cyclohexyl]-3-hydroxy-1,4-naphthoquinone, was studied for its in vitro and in vivo activities against Toxoplasma gondii. Replication within human foreskin fibroblasts of tachyzoites of seven different strains, five of them isolated from AIDS patients, was inhibited by concentrations as low as 4.8 x 10(-9) M. In vivo, a dose of 100 mg/kg of body weight per day, administered by gavage for 10 days, protected 100% of mice against death due to infection with five different strains of T. gondii, including the highly virulent RH strain. A dose of 50 mg/kg/day protected at least 80% of mice infected with the same inoculum, and a dose as low as 9.3 mg/kg/day protected 40 to 60% of mice. Treatment with 50 mg/kg/day for 30 days completely eradicated parasites from mice infected with four of five strains of T. gondii. 566C80 was active in vitro against the cyst stage of T. gondii at concentrations of 50 to 100 micrograms/ml. In vivo activity against this form of T. gondii was examined in mice infected for 6 weeks with strain ME49 and then treated orally with 100 mg of 566C80 per kg per day for 8 weeks. Treated mice sacrificed at 2-week intervals revealed a steady decline in the numbers of cysts in their brains compared with untreated controls. In addition, mortality as well as clinical signs of brain infection was absent from treated mice, whereas control mice had a high mortality rate and showed clinical signs of central nervous system infection. These results reveal remarkable in vitro and in vivo activities of 566C80 against T. gondii.
Test ordering by GP trainees: Effects of an educational intervention on attitudes and intended practice.

OBJECTIVE To assess the effectiveness of an educational intervention on test-ordering attitudes and intended practice of GP trainees, and any associations between changes in test ordering and trainee characteristics. DESIGN Preworkshop and postworkshop survey of attitudes to test ordering, intended test-ordering practices for 3 clinical scenarios (fatigue, screening, and shoulder pain), and tolerance for uncertainty. SETTING Three Australian regional general practice training providers. PARTICIPANTS General practice trainees (N = 167). INTERVENTION A 2-hour workshop session and an online module. MAIN OUTCOME MEASURES Proportion of trainees who agreed with attitudinal statements before and after the workshop; proportion of trainees who would order tests, mean number of tests ordered, and number of appropriate and inappropriate tests ordered for each scenario before and after the workshop. RESULTS Of 167 trainees, 132 (79.0%) completed both the preworkshop and postworkshop questionnaires. A total of 122 trainees attended the workshop. At baseline, 88.6% thought that tests can harm patients, 84.8% believed overtesting was a problem, 72.0% felt pressured by patients, 52.3% believed that tests would reassure patients, and 50.8% thought that they were less likely to be sued if they ordered tests. There were desirable changes in all attitudes after the workshop. Before the workshop, the mean number of tests that trainees would have ordered was 4.4, 4.8, and 1.5 for the fatigue, screening, and shoulder pain scenarios, respectively. After the workshop there were decreases in the mean number of both appropriate tests (decrease of 0.94) and inappropriate tests (decrease of 0.24) in the fatigue scenario; there was no change in the mean number of appropriate tests and a decrease in inappropriate tests (decrease of 0.76) in the screening scenario; and there was an increase in the proportion of trainees who would appropriately not order tests in the shoulder pain scenario. There were no significant associations between changes in test ordering and trainee demographic characteristics or tolerance for uncertainty subscale scores. CONCLUSION General practice trainees have conflicting attitudes to test ordering and demonstrate nonrational test ordering in 3 common scenarios. A workshop on rational test ordering led to desirable changes in attitudes and more rational intended test ordering. Our findings inform the development of appropriate educational interventions that address nonrational testing in family medicine.
Macrophage α1 AMP-activated Protein Kinase (α1AMPK) Antagonizes Fatty Acid-induced Inflammation through SIRT1*

In this study, we aim to determine cellular mechanisms linking nutrient metabolism to the regulation of inflammation and insulin resistance. The nutrient sensors AMP-activated protein kinase (AMPK) and SIRT1 show striking similarities in nutrient sensing and regulation of metabolic pathways. We find that the expression, activity, and signaling of the major isoform α1AMPK in adipose tissue and macrophages are substantially down-regulated by inflammatory stimuli and in nutrient-rich conditions, such as exposure to lipopolysaccharide (LPS), free fatty acids (FFAs), and diet-induced obesity. Activating AMPK signaling in macrophages by 5-aminoimidazole-4-carboxamide-1-β4-ribofuranoside or constitutively active α1AMPK (CA-α1) significantly inhibits; although inhibiting α1AMPK by short hairpin RNA knock-down or dominant-negative α1AMPK (DN-α1) increases LPS- and FFA-induced tumor necrosis factor α expression. Chromatin immunoprecipitation and luciferase reporter assays show that activation of AMPK by CA-α1 in macrophages significantly inhibits LPS- or FFA-induced NF-κB signaling. More importantly, in a macrophage-adipocyte co-culture system, we find that inactivation of macrophage AMPK signaling inhibits adipocyte insulin signaling and glucose uptake. Activation of AMPK by CA-α1 increases the SIRT1 activator NAD+ content and SIRT1 expression in macrophages. Furthermore, α1AMPK activation mimics the effect of SIRT1 on deacetylating NF-κB, and the full capacity of AMPK to deacetylate NF-κB and inhibit its signaling requires SIRT1. In conclusion, AMPK negatively regulates lipid-induced inflammation, which acts through SIRT1, thereby contributing to the protection against obesity, inflammation, and insulin resistance. Our study defines a novel role for AMPK in bridging the signaling between nutrient metabolism and inflammation.
The plastic human brain.

PURPOSE In this review I summarize and discuss reported findings of structural and functional plasticity in the intact human brain. METHODS The main focus is placed on research that uses musicians as a model to study brain plasticity. I summarize therefore mostly studies dealing with musicians or with the effect of music practice. In the first section, structural plasticity is described on the basis of modern neuroanatomical studies using magnetic resonance imaging (MRI) techniques. In the second part, emphasis is given to studies reporting functional plasticity on the basis of changed neurophysiological activation patterns. These studies are discussed in the context of two approaches employed to study plasticity in the human brain: the cross-sectional and longitudinal approaches. RESULTS The reviewed studies altogether indicate that experience can shape brain anatomy and brain physiology. Brain plasticity as demonstrated here is related to changed grey and white mater densities (and volumes) but also to changed activation patterns in the brain areas involved in controlling the expertise task. CONCLUSIONS Taken together, all studies support the view that the human brain is much more plastic than had been anticipated 20 years ago.
ACAT1 gene ablation increases 24(S)-hydroxycholesterol content in the brain and ameliorates amyloid pathology in mice with AD

Cholesterol metabolism has been implicated in the pathogenesis of several neurodegenerative diseases, including the abnormal accumulation of amyloid-β, one of the pathological hallmarks of Alzheimer disease (AD). Acyl-CoA:cholesterol acyltransferases (ACAT1 and ACAT2) are two enzymes that convert free cholesterol to cholesteryl esters. ACAT inhibitors have recently emerged as promising drug candidates for AD therapy. However, how ACAT inhibitors act in the brain has so far remained unclear. Here we show that ACAT1 is the major functional isoenzyme in the mouse brain. ACAT1 gene ablation (A1−) in triple transgenic (i.e., 3XTg-AD) mice leads to more than 60% reduction in full-length human APPswe as well as its proteolytic fragments, and ameliorates cognitive deficits. At 4 months of age, A1− causes a 32% content increase in 24-hydroxycholesterol (24SOH), the major oxysterol in the brain. It also causes a 65% protein content decrease in HMG-CoA reductase (HMGR) and a 28% decrease in sterol synthesis rate in AD mouse brains. In hippocampal neurons, A1− causes an increase in the 24SOH synthesis rate; treating hippocampal neuronal cells with 24SOH causes rapid declines in hAPP and in HMGR protein levels. A model is provided to explain our findings: in neurons, A1− causes increases in cholesterol and 24SOH contents in the endoplasmic reticulum, which cause reductions in hAPP and HMGR protein contents and lead to amelioration of amyloid pathology. Our study supports the potential of ACAT1 as a therapeutic target for treating certain forms of AD.
Trends in number of consultations and antibiotic prescriptions for respiratory tract infections between 1999 and 2005 in primary healthcare in Kalmar County, Southern Sweden

Background. Respiratory tract infections (RTIs) comprise the most common indication for consulting a general practitioner and obtaining an antibiotic prescription. Objective. To study changes in the number of visits, diagnoses, and antibiotic prescriptions for RTI in primary healthcare during the period 1999–2005. Design. A retrospective, descriptive, population-based study of electronic patient records. Setting. County of Kalmar in southeastern Sweden. Patients. Patients visiting primary healthcare units in Kalmar County for an RTI between 1 July 1999 and 31 December 2005. Main outcome measures. RTI diagnoses, antibiotic prescriptions, age groups. Results. A total of 240 447 visits for RTI made between 1999 and 2005 were analysed. The yearly consultation rates for the diagnoses acute tonsillitis and AOM decreased by 12% and 10%, respectively (p = 0.001). Of all patients consulting for an RTI diagnosis, 45% received antibiotics. Of all prescribed antibiotics, 60% were for phenoxymethylpenicillin (PcV) and 18% doxycycline. Amoxicillin or amoxicillin + clavulanic acid was prescribed to a lesser extent. The proportion of patients obtaining an antibiotic prescription was almost constant over time (44–46%). The prescriptions of doxycycline showed increasing values (NS). The prescriptions of remaining antibiotics decreased significantly especially for patients up to middle age. Conclusion. This large population study, comprising more than six years of observations, showed the number of primary healthcare patients receiving an RTI diagnosis decreased during the period 1999–2005, but the proportion of patients receiving an antibiotic prescription remained the same. The large seasonal variations indicate a need for further interventions to decrease antibiotic use for RTIs.
A subset of membrane-associated proteins is ubiquitinated in response to mutations in the endoplasmic reticulum degradation machinery

Ubiquitination of membrane-associated proteins can direct their proteasome-mediated degradation or activation at the endoplasmic reticulum (ER), as well as their endocytosis and intracellular sorting. However, the full spectrum of ubiquitinated membrane proteins has not been determined. Here we combined proteomic analysis with yeast genetics to identify 211 ubiquitinated membrane-associated proteins in Saccharomyces cerevisiae and map >30 precise sites of ubiquitination. Major classes of identified ubiquitinated proteins include ER-resident membrane proteins, plasma membrane-localized permeases, receptors, and enzymes, and surprisingly, components of the actin cytoskeleton. By determining the differential abundance of ubiquitinated proteins in yeast mutated for NPL4 and UBC7, which are major components of ER-associated degradation (ERAD), we furthermore were able to classify 83 of these identified ubiquitinated membrane proteins as potential endogenous substrates of the ERAD pathway. These substrates are highly enriched for proteins that localize to or transit through the ER. Interestingly, we also identified novel membrane-bound transcription factors that may be subject to ubiquitin/proteasome-mediated cleavage and activation at the ER membrane.
HCI usability techniques in agile development

Background: Interest in the integration of the agile software development process (ASDP) and user-centred design (UCD) has grown over the last decade. However, there are not many papers that study this issue holistically and uncover the current state of this integration. Objective: This study sets out to answer the following research question: What is the current state of integration between agile processes and usability techniques? Method: We conduct a systematic mapping study (SMS). A SMS is a form of systematic literature review that aims to identify and classify the research papers published about a specified issue. Results: We retrieved a total of 31 primary studies, suggesting that the agile development community is starting to adopt some usability techniques in its development projects. Most of the human-computer interaction (HCI) techniques that the ASDP is adopting are techniques related to requirements engineering, especially techniques for requirements elicitation and analysis. Judging by the increase in the number of publications over the last decade, the integration of HCI activities and techniques into the ASDP is an issue of notable interest. Conclusions: There are few papers that study the literature holistically and report the current state of usability in the ASDP. Additionally, the literature does not contain a general, formal and systematic proposal to help agile development teams adopt usability techniques in their development projects.
Comparison of intracellular pH transients in single ventricular myocytes and isolated ventricular muscle of guinea‐pig.

1. Intracellular pH was recorded (double‐barrelled pH‐selective microelectrodes) in single ventricular myocytes and whole papillary muscles isolated from guinea‐pig heart. Both preparations were acid‐loaded by various manoeuvres (addition and removal of external NH4Cl or CO2) in order that a comparison could be made of the size and speed of intracellular pH changes and hence of the apparent intracellular buffering power (beta). 2. For the same acid‐loading procedure, the size of intracellular pH (pHi) changes was about threefold larger in the isolated myocyte than in whole papillary muscle. The rate of initial acid loading as well as the subsequent rate of pHi recovery (caused by acid extrusion from the cell) were also threefold faster in the myocyte. Estimates of apparent intrinsic (non‐CO2) buffering power, based upon the size of pHi changes during acid loading, were 15‐20 mmol l‐1 for the myocyte and about 70 mmol l‐1 for whole muscle. This latter value is similar to previous estimates of beta in heart. 3. When acid extrusion was reduced by applying a high dose of amiloride (1 mmol l‐1), then the size of the pHi change during acid loading increased greatly in papillary muscle but changed much less in the myocyte; beta now appeared to be about 30 mmol l‐1 in whole muscle but remained essentially unchanged in the myocyte. 4. We conclude that previous values for beta in cardiac muscle have been greatly overestimated because of the presence of sarcolemmal acid extrusion. Paradoxically, this error in estimating beta is far less evident in the isolated myocyte. We suggest that this is because a much more rapid acid loading is achievable in the myocyte so that acid loading will be blunted less by acid extrusion than in whole muscle. We present a simple mathematical model that demonstrates this phenomenon. We conclude that beta in ventricular muscle is likely to resemble that measured in the isolated myocyte, i.e. 15‐20 mmol l‐1. 5. Slow acid loading in whole ventricular muscle will also affect the kinetics of pHi changes. The model indicates that the rate of pHi recovery from an acid load in papillary muscle does not reflect the pHi dependence of acid extrusion. Instead, it is heavily influenced by the slow rate of acid loading. This emphasises that great care should be taken when interpreting the kinetics of pHi changes in multicellular ventricular preparations.
Inhibition of interleukin-6 receptor directly blocks osteoclast formation in vitro and in vivo.

OBJECTIVE To investigate the efficacy of a murine anti-interleukin-6 receptor (anti-IL-6R) antibody in directly blocking tumor necrosis factor (TNF)- and RANKL-mediated osteoclastogenesis in vitro and in vivo. METHODS The efficacy of a murine antibody against IL-6R in blocking osteoclast differentiation of mononuclear cells stimulated with RANKL was tested. In addition, arthritic human TNFalpha-transgenic mice were treated with anti-IL-6R antibody, and osteoclast formation and bone erosion were assessed in arthritic paws. RESULTS Blockade of IL-6R dose dependently reduced osteoclast differentiation and bone resorption in monocyte cultures stimulated with RANKL or RANKL plus TNF. In human TNFalpha-transgenic mice, IL-6R blockade did not inhibit joint inflammation, but it strongly reduced osteoclast formation in inflamed joints as well as bone erosion in vivo. Neither the cell influx into joints nor the synovial expression of IL-6 and RANKL changed with IL-6R blockade, while the synovial expression of IL-1 was significantly reduced. In contrast, TNF-mediated systemic bone loss was not inhibited by IL-6R blockade. CONCLUSION These data suggest that blockade of IL-6R directly affects osteoclast formation in vitro and in vivo, suggesting a direct and specific effect of anti-IL-6R therapy on osteoclasts independently of its antiinflammatory effects. This effect adds significantly to the structure-sparing potential of pharmacologic blockade of IL-6R in arthritis.
Proton magnetic resonance spectroscopic imaging of cerebral gliomas: correlation of metabolite ratios with histopathologic grading.

BACKGROUND Magnetic resonance spectroscopic imaging (MRSI) can provide spatially encoded metabolite information and improve tissue specificity in human brains. The major goal of this study was to evaluate the correlation of metabolite ratios measured by MRSI with histopathological grading of cerebral gliomas. METHODS Twenty-seven patients with cerebral gliomas were referred consecutively for pre-surgical evaluation. The lesions included 10 grade II, 5 grade III, and 12 grade IV gliomas. MRSI data were acquired during the same session of conventional magnetic resonance imaging and analyzed in terms of N-acetylaspartate (NAA), creatine-phosphocreatine (Cr), choline-containing compounds (Cho), and lactate. RESULTS There were significantly lower NAA/Cr and higher Cho/Cr, Cho/NAA and (Cho+Cr)/NAA ratios (ps < 0.001) in gliomas than in normal tissues. There were significantly lower NAA/Cr and higher Cho/NAA and (Cho+Cr)/NAA ratios (ps < or = 0.05) in World Health Organization (WHO) grade III or IV gliomas than in grade II gliomas. A significant correlation was identified between the (Cho+Cr)/NAA ratio and WHO grade (p < 0.05). There was no significant metabolite difference between grade III and grade IV tumors (ps > 0.1), or significant difference in lactate occurrence rates among different grades (p = 0.26). CONCLUSIONS Proton MRSI can provide in vivo information about the metabolic status of cerebral gliomas, and the (Cho+Cr)/NAA ratio can discriminate different grades better than other metabolite ratios. However, substantial overlap of metabolite ratios among different severities of malignancy makes it impossible to confirm the WHO grade of a specific cerebral glioma by using clinical MRSI.
Le feu, la brousse et la savane. Modélisation spatiale de la dynamique des paysages soudaniens (Burkina Faso)

Dans les paysages soudaniens, embrases lors de la saison seche, les importantes mutations engendrees par l'intensification agricole recomposent les espaces et les modes de gestion associes. Dans ce contexte, le feu, symbole passe de la degradation des forets devient un outil d'ingenierie ecologique aux services des savanes desormais menacees. Afin d'analyser ces bouleversements complexes des paysages-objets et des representations associees aux enjeux modernes qui se tissent, une caracterisation spatiale fine du feu a ete entreprise. Ce travail, central dans la recherche menee, permet alors d'apprehender l'evolution des modes de gestion et les trajectoires paysageres. Contrairement aux observations releguant les pratiques du feu comme anecdotiques ou anarchiques en saison seche, nous montrons que la dynamique complexe des feux de brousse est principalement structuree par la combinaison locale d'une pratique reguliere et de facteurs pedoclimatiques. L'interaction locale entre le moment de la mise a feu et la combustibilite de la vegetation est le critere determinant des regimes de feux observes a l'echelle regionale. Les dernieres pluies correspondent ainsi a l'eclosion des premiers feux sur les sols squelettiques, puis petit a petit, les feux parcourent des milieux aux sols plus profonds ou la vegetation reste humide plus longtemps. Le recours a l'analyse et a la simulation spatiale a permis de faciliter les echanges entre observations de terrain et cartes regionales, pour ainsi explorer les interactions locales entre mise a feu et dynamique saisonniere des espaces. Cependant si cette dynamique saisonniere est confirmee, elle devoile au-dela-des variables biophysiques, la place nouvelle des territoires dedies a la protection de la nature et l'heterogeneite des regards portes sur la gestion des espaces ruraux.