Miracle-dz/UniFAR-FTUs huggingface dataset:
Effects of Muscle Strengthening around the Hip on Pain, Physical Function, and Gait in Elderly Patients with Total Knee Arthroplasty: A Randomized Controlled Trial

Background: Functional limitations may still remain even after a patient completes a traditional quadriceps-based rehabilitative program after total knee arthroplasty. Based on studies reporting that patients with knee osteoarthritis have muscle weakness around the hip joint after total knee arthroplasty, we investigated whether strengthening the hip muscles can reduce pain and improve the physical function and gait of patients who underwent total knee arthroplasty. Methods: Patients were randomly divided into three groups: hip, quadriceps, and control. The hip group (n = 19) completed an extensor, adductor, and external muscle strengthening exercise program. The quadriceps group (n = 20) completed a quadriceps strengthening exercise program. The control group (n = 16) completed an active range of motion exercises. Therapy was conducted thrice weekly for 12 weeks. Pain and function items from the Western Ontario and McMaster Universities Osteoarthritis Index, Alternate Step Test, Five Times Sit to Stand Test, and Single Leg Stance Test were performed to assess pain and physical function. In the gait analysis, stride, single-stance (%), double-stance (%), and gait speed were measured. Data were collected at baseline and at 4, 8, and 12 weeks after the intervention. Results: The hip group showed more significant improvements in pain and performance on the Alternate Step Test and Single Leg Stance Test than the quadriceps and control groups. In the gait analysis, the hip group showed the largest improvements in single stance and double stance. Conclusions: In conclusion, a 12-week hip muscle strengthening exercise program effectively improves the physical function and gait of patients who have undergone total knee arthroplasty.
Melanin as a Virulence Factor in Different Species of Genus Paracoccidioides

Paracoccidioidomycosis (PCM) is a granulomatous systemic mycosis caused by the thermo-dimorphic fungi of the genus Paracoccidioides. Melanin production by fungi can affect their pathogenesis and virulence. This study evaluates the production of melanin by different isolates of genus Paracoccidioides and examines how the presence of this polymer affects yeast cell phagocytosis, as well as laccase enzyme production. The results obtained showed that the isolates of genus Paracoccidioides: P. lutzii (Pb01, Pb66, ED01, Pb1578, and Pb8334), P. restrepiensis (PS3-Pb60855), P. brasiliensis (S1-Pb18), and P. americana (PS2-Pbcão) produce melanin in the presence of L-3,4-dihydroxyphenylalanine (L-DOPA). Phagocytosis assays were carried out with peritoneal macrophages from C57Bl/6 mice that were challenged with Pb18, Pb60855, and Pb01. We observed that melanin interferes with phagocytosis in the presence or absence of complement or heat-inactivated serum. This article confirms that different species of the genus Paracoccidioides produce melanin in different magnitudes and that the polymer functions as a virulence factor.
Investigation of the effects of substitution levels, assay methods and length of adaptation to experimental diets on determined metabolisable energy value of maize, barley and soya bean meal

ABSTRACT 1. Two experiments were carried out to investigate the influence of substitution levels, assay methods and adaptation length of broilers to experimental diets on metabolisable energy of corn and barley (Experiment 1) and soya bean meal (Experiment 2). In each experiment, the test feedstuffs proportionately replaced the reference diet at the rates of 150, 300 or 450 g/kg. Each treatment had 8 or 7 replicate cages containing three birds per cage. Broiler chickens were adapted to experimental diets for either 7 or 4 d prior to excreta collection on d 20 and 21. 2. Metabolisable energy was determined using the difference method at each substitution level and the regression method, using the 4 combinations of the substitution levels. 3. In Experiment 1, AME and AMEn were lower (P < 0.01) for barley than for maize, irrespective of the assay method and there was a trend for an adaptation × cereal grains interaction (P < 0.10) for AME determined by the difference regression method. For maize, AME and AMEn calculated using regression or the difference method were not significantly different, whereas barley AME and AMEn values were greater (P < 0.01) when derived using regression analysis. 4. In Experiment 2, there was no significant adaptation length × substitution levels interaction. The AME and AMEn values were lowest (P < 0.01) at 150 g/kg SBM inclusion level when calculated using the difference method. On the other hand, AME and AMEn values determined by the regression method were not influenced by substitution levels. 5. It was concluded that the influence of substitution levels on assayed metabolisable energy is feedstuff-dependent and that the regression method produced more consistent metabolisable energy values in a feedstuff-independent manner.
How directed evolution reshapes energy landscapes in enzymes to boost catalysis

Two steps forward—now look back Whether designed computationally or uncovered in activity screening, enzymes repurposed for biocatalysis rarely start at the peak of proficiency. However, directed evolution can in some cases increase catalytic efficiency of a poor enzyme by many orders of magnitude. Otten et al. used a suite of biochemical techniques to investigate the origins of rate enhancement in a previously evolved model enzyme. Two conformational states are present in the initial, computationally designed enzyme, but only one is active. Shifting the population toward the active state is one factor in increasing catalytic efficiency during evolution. Single mutations do not greatly increase activity, but the synergistic combination of just two out of 17 substitutions can provide most of the rate enhancement seen in the final, evolved enzyme. Science, this issue p. 1442 Altered sampling of conformational substates was critical for optimization of a designer enzyme. The advent of biocatalysts designed computationally and optimized by laboratory evolution provides an opportunity to explore molecular strategies for augmenting catalytic function. Applying a suite of nuclear magnetic resonance, crystallography, and stopped-flow techniques to an enzyme designed for an elementary proton transfer reaction, we show how directed evolution gradually altered the conformational ensemble of the protein scaffold to populate a narrow, highly active conformational ensemble and accelerate this transformation by nearly nine orders of magnitude. Mutations acquired during optimization enabled global conformational changes, including high-energy backbone rearrangements, that cooperatively organized the catalytic base and oxyanion stabilizer, thus perfecting transition-state stabilization. The development of protein catalysts for many chemical transformations could be facilitated by explicitly sampling conformational substates during design and specifically stabilizing productive substates over all unproductive conformations.
Beneficial effect of oral administration of zinc sulfate on 5-fluorouracil-induced gastrointestinal mucositis in rats.

OBJECTIVE This experimental study explored the potential of oral zinc sulfate to protect the gut mucosa from 5-fluorouracil (5-FU)-induced degenerative lesions in Wistar rats. MATERIALS AND METHODS Female Wistar rats were used and divided into 2 interventional groups (Z with 6 animals and F with 5 animals) and one control group (M with 5 rats). After 2 hours of fasting, group Z received via oral gavage 1.5 ml of solution, corresponding to 15 mg zinc sulfate for 9 consecutive days. Groups F and M received only the vehicles. On day 3, 400 mg/kg of 5-FU was administered intraperitoneally to groups Z and F. Tissue samples were collected from the duodenum, jejunum, colon and liver. Histological assessment for each gastrointestinal tract segment was determined semi-quantitatively by rating 11 histological features from normal (0) to severe (3). The independent groups were analyzed using the Kruskal-Wallis test and the Mann-Whitney U-test, with a Bonferroni correction for alpha (p ≤ 0.016). RESULTS In group F the jejunum was the most affected area with a mean histological score of 27 (25-32). In the Z group, significantly lower histological scores were obtained compared with group F (duodenum Z vs. F: U = 0, p = 0.004; jejunum Z vs. F: U = 0, p = 0.006 and colon: Z vs. F: U = 0, p = 0.005). Graded liver necro-inflammatory lesions were significantly lower in group Z compared with group F (U = 0, p = 0.004), suggesting fewer bacterial intestinal translocation processes. CONCLUSIONS Zinc sulfate has a beneficial role, decreasing the severity of gut mucosal injuries induced by 5-FU in Wistar rats.
Respiratory, cardiac and metabolic responses during electrical muscle stimulation in quadriceps muscle versus comparable voluntary muscle contractions

Abstract Electrical Muscle Stimulation (EMS) and voluntary muscle contraction (VMC) are both acceptable rehabilitative modalities to preserve muscle strength loss. The study aimed to compare respiratory, metabolic, and cardiac parameters during quadriceps muscle contraction (QMC) using either EMS or VMC with comparable generated low intensity muscle force. Thirty healthy non-smoker males, age 20–58 years with normal BMI and low to moderate physical activity, underwent two 20-min sessions of comparable QMC using EMS vs VMC at the same day. The BIODEX III isokinetic dynamometer was used to assess maximum isometric force and the comparable force generated during each condition (EMS vs VMC), while the METAMAX 3B portable metabolic system was used to measure continuously the physiological parameters. Tolerable EMS was used (mean: 33 ± 1.5 mA, at 75 Hz). Each contraction lasted 10 sec followed by 20 sec rest. Paired t-tests were used for comparisons between sessions. A relatively low proportion of maximum isometric force (EMS: 8.5% vs VMC: 8.6%) and torque (EMS: 16 ± 1.3 vs VMC: 16 ± 1.1 Nm) were generated during each session. Mean minute ventilation (EMS: 10.8 L vs VMC: 9.8 L), tidal volume (EMS: 0.6 L vs VMC: 0.5 L), O2 uptake (EMS: 0.31 L/min vs VMC: 0.26 L/min) and O2 pulse (EMS: 3.9 ml/beat vs VMC: 3.6 ml/beat) were different between sessions (p ≤ .05); while heart rate (EMS: 72 beats/min vs VMC: 71 beats/min) was equal. Quadriceps muscle EMS induces higher respiratory and metabolic responses compared to equal magnitude VMC in healthy males.
Item response theory analysis of the Clinical Dementia Rating

The Clinical Dementia Rating (CDR) is widely used in Alzheimer's disease research studies and has well established reliability and validity. To facilitate the development of an online, electronic CDR (eCDR) for more efficient clinical applications, this study aims to produce a shortened version of the CDR, and to develop the statistical model for automatic scoring.
SARS-CoV-2 viral budding and entry can be modeled using BSL-2 level virus-like particles

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was first discovered in December 2019 in Wuhan, China, and expeditiously spread across the globe causing a global pandemic. Research on SARS-CoV-2, as well as the closely related SARS-CoV-1 and MERS coronaviruses, is restricted to BSL-3 facilities. Such BSL-3 classification makes SARS-CoV-2 research inaccessible to the majority of functioning research laboratories in the United States; this becomes problematic when the collective scientific effort needs to be focused on such in the face of a pandemic. However, a minimal system capable of recapitulating different steps of the viral life cycle without using the virus’ genetic material could increase accessibility. In this work, we assessed the four structural proteins from SARS-CoV-2 for their ability to form virus-like particles (VLPs) from human cells to form a competent system for BSL-2 studies of SARS-CoV-2. Herein, we provide methods and resources of producing, purifying, fluorescently and APEX2-labeling of SARS-CoV-2 VLPs for the evaluation of mechanisms of viral budding and entry as well as assessment of drug inhibitors under BSL-2 conditions. These systems should be useful to those looking to circumvent BSL-3 work with SARS-CoV-2 yet study the mechanisms by which SARS-CoV-2 enters and exits human cells.
Cannabinoid Type 1 Receptor is Undetectable in Rodent and Primate Cerebral Neural Stem Cells but Participates in Radial Neuronal Migration

Cannabinoid type 1 receptor (CB1R) is expressed and participates in several aspects of cerebral cortex embryonic development as demonstrated with whole-transcriptome mRNA sequencing and other contemporary methods. However, the cellular location of CB1R, which helps to specify molecular mechanisms, remains to be documented. Using three-dimensional (3D) electron microscopic reconstruction, we examined CB1R immunolabeling in proliferating neural stem cells (NSCs) and migrating neurons in the embryonic mouse (Mus musculus) and rhesus macaque (Macaca mulatta) cerebral cortex. We found that the mitotic and postmitotic ventricular and subventricular zone (VZ and SVZ) cells are immunonegative in both species while radially migrating neurons in the intermediate zone (IZ) and cortical plate (CP) contain CB1R-positive intracellular vesicles. CB1R immunolabeling was more numerous and more extensive in monkeys compared to mice. In CB1R-knock out mice, projection neurons in the IZ show migration abnormalities such as an increased number of lateral processes. Thus, in radially migrating neurons CB1R provides a molecular substrate for the regulation of cell movement. Undetectable level of CB1R in VZ/SVZ cells indicates that previously suggested direct CB1R-transmitted regulation of cellular proliferation and fate determination demands rigorous re-examination. More abundant CB1R expression in monkey compared to mouse suggests that therapeutic or recreational cannabis use may be more distressing for immature primate neurons than inferred from experiments with rodents.
What dominates the changeable pharmacokinetics of natural sesquiterpene lactones and diterpene lactones: a review focusing on absorption and metabolism

Abstract Sesquiterpene lactones (STLs) and diterpene lactones (DTLs) are two groups of common phytochemicals with similar structures. It’s frequently reported that both exhibit changeable pharmacokinetics (PK) in vivo, especially the unstable absorption and extensive metabolism. However, the recognition of their PK characteristics is still scattered. In this review, representative STLs (atractylenolides, alantolactone, costunolide, artemisinin, etc.) and DTLs (ginkgolides, andrographolide, diosbulbins, triptolide, etc.) as typical cases are discussed in detail. We show how the differences of treatment regimens and subjects alter the PK of STLs and DTLs, with emphasis on the effects from absorption and metabolism. These compounds tend to be quite permeable in intestinal epithelium, but gastrointestinal pH and efflux transporters (represented by P-glycoprotein) have great impact and result in the unstable absorption. As the only characteristic functional moiety, the metabolic behavior of lactone ring is not dominant. The α, β-unsaturated lactone moiety has the strongest metabolic activity. While with the increase of low-activity saturated lactone moieties, the metabolism is led by other groups more easily. The phase I (oxidation, reduction and hydrolysis reaction) and II metabolism (conjugation reaction) are both extensive. CYP450s, mainly CYP3A4, are largely involved in biotransformation. However, only UGTs (UGT1A3, UGT1A4, UGT2B4 and UGT2B7) has been mentioned in studies about phase II metabolic enzymes. Our work offers a beneficial reference for promoting the safety evaluation and maximizing the utilization of STLs and DTLs.
Cost-effectiveness of pharmacist-led care versus usual care in type 2 diabetic Jordanians: a Markov modeling of cardiovascular diseases prevention

ABSTRACT Background Cardiovascular diseases (CVDs) are responsible for one third of global deaths and the main cause of death among Jordanians. Pharmacist-led care was outlined previously as a cost-effective approach in the management of chronic illness; however, this is not well studied in low to middle-income countries. Aim and objectives To assess the cost-effectiveness of pharmacist-led care versus usual care in preventing CVDs in Type 2 Diabetes Mellitus (T2DM). Method A Markov model of one-year cycle length and 10-year time horizon was constructed to simulate 10-year CVD events, mortality, and costs for two hypothetical cohorts; usual care and pharmacist-led care, respectively, of Jordanian patients suffering from T2DM. Public health provider perspective was adopted. Outcomes examined were incremental costs, LYGs, and incremental cost-effectiveness ratio (ICER). Deterministic and probabilistic sensitivity analysis (PSA) assessed the robustness of the results. Result The pharmacist-led care generated an additional 0.3 LYG/patient at an additional cost of JD1,238.78 (US$1,747.24) comparing to the usual care in the 10-year base-case analysis. Deterministic and PSA supported the robustness of base-case findings, indicating that pharmacist-led care is cost-effective. Conclusion The findings outline long-term clinical and economic benefits of expanding clinical pharmacist’s roles in direct patient care services.
Thermal investigations on polymer dispersed liquid crystal composites and thermo-electric polymer composites using photothermal techniques

Dans une premiere partie, une nouvelle methodologie, precise et hautement sensible de caracterisation des parametres thermiques de liquides par radiometrie photothermique est ici presentee. Deux configurations experimentales sont proposees. Elles ont ete testees et validees avec des materiaux liquides usuels aux parametres thermiques connus. Par la suite, cette demarche a ete utilisee pour l'etude de polymeres disperses dans des cristaux liquides. Les proprietes thermiques dynamiques de chaque echantillon ont ete mesurees en fonction de l'amplitude du champ electrique applique a une frequence donnee aussi bien qu'en fonction de la frequence du champ electrique a une amplitude fixe. Cette etude a montre que les proprietes thermiques etaient sujettes aux effets du champ de depolarisation aux basses frequences. La seconde partie de ce manuscrit decrit la nouvelle technique photothermique basee sur l'effet thermoelectrique. Cette technique est utile pour caracteriser thermiquement les materiaux thermoelectriques sans avoir a recourir a un capteur exterieur pour mesurer le changement de temperature. Une etude theorique et experimentale est presentee. Ces experiences ont ete realisees avec des composites polyaniline/nanotubes de carbone par mesure de la tension generee par l'echantillon thermoelectrique chauffe par un faisceau laser. Des mesures additionnelles a l'aide de la radiometrie infrarouge sur ces memes echantillons ont ete entreprises et les resultats sont en bon accord avec ceux precedemment trouves. Enfin, la possibilite d'utiliser les materiaux thermoelectriques comme capteur photothermique au travers d'une cavite resonnante a ondes thermiques est evoquee.
Etude d'une famille de gènes d'Arabidopsis thaliana homologues de la lécithine cholestérol acyltransférase humaine : Caractérisation d'une nouvelle phospholipase A1 et étude d'une stérol acyltransférase

La cellule vegetale regule sa teneur en sterols membranaires en esterifiant l'exces de sterols par des acides gras. L'enzyme qui catalyse cette reaction d'esterification, une sterol acyltransferase, n'etait pas caracterisee chez les vegetaux. Quatre genes d'Arabidopsis thaliana presentent des homologies significatives avec HsLCAT, le gene de la lecithine cholesterol acyltransferase humaine, la proteine qui esterifie le cholesterol dans le plasma. Ces quatre genes AtLCAT1, AtLCAT2, AtLCAT3 et AtLCAT4 ont ete exprimes dans la levure et/ou dans les plantes. Deux d'entre eux ont ete caracterises. AtLCAT3 code une phospholipase A1, une enzyme hydrolysant specifiquement les acides gras en position sn1 des phospholipides. La transformation de la levure par ce gene conduit a un doublement de la quantite de triglycerides, une augmentation des acides gras totaux de 40%, et a une forte perturbation du metabolisme lipidique. AtLCAT2 code une sterol acyltransferase. La surexpression de la proteine par transgenese dans A. Thaliana ne modifie pas la teneur en esters de sterols dans les plantes entieres, mais l'augmente dans des cals derivant de ces plantes. Deux lignees mutantes comportant une insertion d'un T-DNA dans le gene AtLCAT2 ont ete analysees. Leur quantite d'esters de sterols est reduite de 75% environ par rapport aux lignees temoins. L'acide mevalonique, precurseur des sterols et stimulateur de leur biosynthese, a des effets toxiques sur ces lignees mutantes.
Knowledge, Attitudes and Perceptions of Medical Students on Antimicrobial Stewardship

Antimicrobial Resistance (AMR) is an ongoing threat to modern medicine throughout the world. The World Health Organisation has emphasized the importance of adequate and effective training of medical students in wise prescribing of antibiotics Furthermore, Antimicrobial Stewardship (AMS) has been recognized as a rapidly growing field in medicine that sets a goal of rational use of antibiotics in terms of dosing, duration of therapy and route of administration. We undertook the current review to systematically summarize and present the published data on the knowledge, attitudes and perceptions of medical students on AMS. We reviewed all studies published in English from 2007 to 2020. We found that although medical students recognize the problem of AMR, they lack basic knowledge regarding AMR. Incorporating novel and effective training methods on all aspects of AMS and AMR in the Medical Curricula worldwide is of paramount importance.
Influence of species of negative control sera on results of a brucellosis fluorescence polarization assay

We evaluated serologic responses of cattle, bison, elk, and swine representing negative control, early vaccination (4–8 wk), late vaccination (21–28 wk) or booster vaccination, early after-experimental challenge (2–4 wk), and late after-experimental challenge (8–21 wk), in a brucellosis fluorescence polarization assay (FPA; n = 10 sera per species per treatment) using negative control sera from cattle, bison, elk, and swine (n = 5 per species). Sera from cattle shedding Brucella abortus strain RB51 in milk were also evaluated against the 20 negative control sera. The species of negative control sera used in the FPA could increase (p < 0.05) delta millipolarization (mP; delta mP = sample mP − negative control mP) results. In general, the species of negative control sera did not alter the interpretation of FPA results in control, vaccinated, or infected animals. Even after repeated RB51 vaccinations in bison, cattle, or elk, or in cattle shedding RB51 in milk, serologic results from the FPA remained negative. Species differences in FPA results were noted; elk developed robust humoral responses very quickly after infection that resulted in strong positive FPA results. In cattle and bison, humoral responses appeared to develop over a longer period of time, and greater delta mP values were detected at later times after infection. Sensitivity of the FPA for detecting infected animals was greatest for elk in early challenge samples and bison in late challenge samples. Our data suggest that species of origin of negative control sera does not influence interpretation of the FPA in natural hosts of Brucella abortus.