Miracle-dz/UniFAR-FTUs huggingface dataset:
The effect of proteolytic enzyme serratiopeptidase in the treatment of experimental implant-related infection.

BACKGROUND Infection around an implanted orthopaedic device is a devastating complication, and the treatment of infections involving slime-forming bacteria is especially difficult. The purpose of the present study was to evaluate the effectiveness of a proteolytic enzyme, serratiopeptidase, in the eradication of a periprosthetic infection in an in vivo animal model. METHODS In sixty Sprague-Dawley rats, the medullary canal of the right femur was drilled through the intercondylar notch and was inoculated with a Staphylococcus epidermidis strain (ATCC 35984) with a high slime-producing capacity. The cavity was filled with polymethylmethacrylate cement, and a Kirschner wire that had contact with the knee joint was inserted. None of the animals received any treatment for two weeks. Twenty rats were killed at two weeks after the inoculation in order to determine if the infection had become established. The remaining forty rats were randomized into two groups. One group received serratiopeptidase enzyme injections into the knee joint in addition to antibiotic therapy for four weeks, and the other group received intra-articular saline solution injections together with the same antibiotic therapy. The animals from both groups were killed two weeks after the end of therapy (on Day 56). The knee specimens were evaluated bacteriologically and histologically to determine the prevalence of persistent infection and the effects of the enzyme on local tissue. RESULTS At two weeks, inoculated bacteria grew on culture of specimens from twelve (63.2%) of nineteen animals in the no-treatment group. Microbiological testing suggested that infection persisted in only one (5.6%) of eighteen animals in the serratiopeptidase-and-antibiotic group, whereas it was present in six (37.5%) of sixteen animals in the antibiotic-only group (p = 0.001). Histological evaluation showed similar results (kappa = 0.92). CONCLUSIONS Serratiopeptidase was effective for eradicating infection caused by biofilm-forming bacteria in this experimental animal model. The antibiofilm property of the enzyme may enhance antibiotic efficacy in the treatment of staphylococcal infections.
p27 downregulation and metallothionein overexpression in gastric cancer patients are associated with a poor survival rate

As a significant number of curatively treated gastric cancer patients will ultimately relapse, there is an urgent need to investigate new prognostic markers for identification of high‐risk patients. In this study, we investigated the possible role of molecular markers involved in cell cycle regulation (B1 and D3 cyclins, and p27) and cell protection (metallothionein, MT) in predicting tumor behavior and clinical outcome in gastric cancer patients.
The Role of TNF-&agr; 308G>A Polymorphism in the Risk for Ischemic Stroke

Background:Stroke is a common health problem; however, its pathogenesis is not clear. Several studies have examined the association of −308G>A promoter polymorphism in the tumor necrosis factor-&agr; gene (TNF-&agr;) with ischemic stroke susceptibility. However, the results of these studies are inconsistent and the sample sizes of most of the studies were small. Thus, a meta-analysis was conducted to provide a more robust estimate of the effect of the TNF-&agr; 308G>A polymorphism on the risk for ischemic stroke. Methods:Odds ratios with 95% confidence intervals were used to assess the strength of the association of TNF-&agr; polymorphisms with ischemic stroke. Cochran's Q statistic and the inconsistency index (I2) were used to explore heterogeneity. Egger's test and inverted funnel plots were used to investigate publication bias. Results:Thirteen studies met the inclusion criteria involving 3515 cases and 3949 controls. A significant association was found between TNF-&agr; 308G>A polymorphism and the development of ischemic stroke in the Asian population. However, no statistically significant association was observed in the overall analysis and in the Caucasian population. In the subgroup analysis by age, a significant association was found in the juvenile and adult populations, showing that TNF-&agr; 308G>A polymorphism is associated with the risk for juvenile ischemic stroke. Conclusions:This study suggests that TNF-&agr; 308G>A polymorphism is associated with the risk for juvenile ischemic stroke, whereas it is a protective factor for ischemic stroke in Asians and the adult population. However, in the overall analysis and in Caucasians, a significant association was not found.
Inhibition of Diabetes by an Insulin-Reactive CD4 T-Cell Clone in the Nonobese Diabetic Mouse

A cloned Thl cell line was isolated from pancreatic lymph nodes of NOD mice that carries a T-cell receptor encoding Vβ14 and proliferates in response to NOD islets, islet supernatant, and crystalline bovine and rat insulin, specifically to a B-chain peptide bound to IAg7. The response to islet supernatant was reduced by 75% by anti-insulin antibody treatment. The insulin-reactive clone reduced insulitis and totally blocked the development of spontaneous diabetes in NOD mice (n = 8) as well as the adoptive transfer of diabetes into irradiated NOD mice following the injection of splenocytes from diabetic mice (n = 13). Trafficking of the adoptively transferred cells was assessed by labeling the clone or diabetic splenocytes with a fluorescent marker (Dil). The labeled clone was detected in the islet periphery, whereas labeled splenocytes alone invaded the islets by 3 days. In contrast, the protective clone dramatically delayed and reduced the number of labeled diabetic splenocytes infiltrating the islet, although their appearance in the spleen was unaffected. In vitro, the clone as well as supernatant derived from the clone blocked the proliferation of diabetic NOD splenocytes to islets. This inhibitory effect was diminished by anti–transforming growth factor-β. In conclusion, an insulin-specific Thl cell was isolated from NOD mice that traffics to the islet and prevents the spontaneous development and the adoptive transfer of diabetes. It appears to act locally by releasing transforming growth factor-β and/or other factors that inhibit homing to and/or proliferation of diabetic splenocytes within the islet. These findings may provide insights into and suggest mechanisms for the protective effects of insulin therapy against diabetes.
Gross motor outcomes in children with hemiparesis involved in a modified constraint-induced therapy program.

OBJECTIVE Constraint-Induced Therapy (CIT) has been used in pediatric rehabilitation and targets upper extremity (UE) outcomes. The purpose of this study was to measure concurrent gross motor and lower extremity functional changes using the Gross Motor Function Measure (GMFM) before and after a modified UE CIT program. The Assisting Hand Assessment (AHA) was used to evaluate upper extremity outcomes. DESIGN Before-after trial design of a 19-day outpatient CIT program at Seattle Children's Hospital in Seattle, WA, USA of six ambulatory children with spastic hemiparesis between the ages of 5 and 11 years with GMFCS scores of 1. GMFM Section D (Standing) and E (Walking, Running, Jumping) and AHA scores were obtained before and after a modified CIT program. RESULTS Significant differences were found between pre and post-CIT AHA and GMFM section D and E scores (p < 0.05). All children improved from baseline, yet the child with the lowest initial scores revealed the greatest improvements. CONCLUSIONS Improvements in GMFM and AHA scores were noted after a modified CIT program. Such data suggests that CIT may also influence rehabilitation outcomes not only specific to the upper extremity and warrants further investigation.
Processing speed in recurrent visual networks correlates with general intelligence

Studies on the neural basis of general fluid intelligence strongly suggest that a smarter brain processes information faster. Different brain areas, however, are interconnected by both feedforward and feedback projections. Whether both types of connections or only one of the two types are faster in smarter brains remains unclear. Here we show, by measuring visual evoked potentials during a texture discrimination task, that general fluid intelligence shows a strong correlation with processing speed in recurrent visual networks, while there is no correlation with speed of feedforward connections. The hypothesis that a smarter brain runs faster may need to be refined: a smarter brain's feedback connections run faster.
Ground reaction forces and kinematics of plant leg position during instep kicking in male and female collegiate soccer players

The players' ability to achieve the greatest distance in kicking is determined by their efficiency in transferring kinetic energy from the body to the ball. The purpose of this study was to compare the kinetics and kinematics of the plant leg position between male and female collegiate soccer players during instep kicking. Twenty-three soccer players (11 males and 12 females) were filmed in both the sagittal and posterior views while performing a maximal instep kick. Plant leg kinetic data were also collected using an AMTI 1000 force platform. There were no significant differences between the sexes in plant leg position, but females had significantly greater trunk lean, plant leg angle, and medial-lateral ground reaction force than the males. Males showed higher vertical ground reaction forces at ball contact, but there were no significant differences in ball speed at take-off between the sexes. Ball speed at take-off was inversely related to peak anterior–posterior ground reaction force ( − 0.65). The anatomical differences between the sexes were reflected in greater trunk lean and lower leg angle in the females.
The Menstrual Cycle and Human Performance: An Overview

Physiological events during the normal menstrual cycle are determined by feedback loops within the hypothalamic-pituitary-ovarian axis. Hormonal changes within the menstrual cycle have potential impact on human performance. Relevant stages to consider are pre-menses and menses, the follicular and luteal phases separated by an abrupt elevation in lutenizing hormone and characterised by a sharp rise in body temperature coinciding with ovulation. Strenuous athletic training may affect the normal menstrual cycle. Such disruptions include delayed menarche in ballet dancers and gymnasts, shortened luteal phase and secondary amenorrhea associated with high training loads and competitive stress. Amenorrhea is also noted in flight attendants, linked with an inhibiting effect of disrupted circadian rhythm on lutenizing hormone. The so-called 'athlete triad' considers secondary amenorrhea, abnormal eating behaviour and osteoporosis (attributed to chronic hypoestrogenia). The normal cycle may also be disrupted when circadian rhythms are disturbed, for example in rapid time-zone transitions. Fluctuations in the steroid hormones have been associated with changes in muscle strength. There is evidence also of elevations in heart rate: changes may be partly specific to time of day. Effects on muscle strength may be determined at selected stages of the menstrual cycle, using whole-body performance, local muscle groups or isolated individual muscles. Whilst oestrogen has been implicated in the ergogenic effect of steroid hormones, there is accumulating evidence that a role for progesterone cannot be discounted. The isolation of the ovarian hormones separately is feasible with studies of IVF patients or groups on hormone replacement therapy.
Interhemispheric Interaction During Childhood: II. Children With Early-Treated Phenylketonuria

This study examined whether children with early-treated phenylketonuria (ETPKU) exhibited a disruption in communication between the hemispheres as a function of computational complexity (Banich & Belger, 1990; Belger & Banich, 1992, 1998) when compared to neurologically uncompromised children who were matched in age and IQ. This investigation was motivated by findings that phenylketonuria affects myelination of neurons, including those that make up the corpus callosum, the main neural conduit for interhemispheric interaction. Children performed 2 tasks: a less complex physical-identity task and a more complex name-identity task. For both tasks, we compared performance on across-hemisphere trials, which require interhemispheric interaction, and on within-hemisphere trials, in which no hemispheric interaction is required. On the more complex name-identity task, children with ETPKU exhibited less of a benefit from across-hemisphere processing than did neurologically intact children. These results suggest that the interhemispheric interaction required to complete computationally complex tasks is compromised in children with ETPKU. Such an insufficiency may explain some of the attentional deficits observed in this group of children.
Charting the Signal Trajectory in a Light-Oxygen-Voltage Photoreceptor by Random Mutagenesis and Covariance Analysis*

Background: Modular receptors like the photoreceptor YF1 detect signals and process them into biological responses. Results: We identify numerous residues in the photosensor module of YF1 governing signal detection and processing. Conclusion: Spatial clustering of these residues delineates structurally contiguous regions in the photosensor crucially involved in signal transduction. Significance: The underlying mechanistic principles are widely shared in signal receptors. Modular signal receptors empower organisms to process environmental stimuli into adequate physiological responses. At the molecular level, a sensor module receives signals and processes the inherent information into changes of biological activity of an effector module. To better understand the molecular bases underpinning these processes, we analyzed signal reception and processing in the dimeric light-oxygen-voltage (LOV) blue light receptor YF1 that serves as a paradigm for the widespread Per-ARNT-Sim (PAS) signal receptors. Random mutagenesis identifies numerous YF1 variants in which biological activity is retained but where light regulation is abolished or inverted. One group of variants carries mutations within the LOV photosensor that disrupt proper coupling of the flavin-nucleotide chromophore to the protein scaffold. Another larger group bears mutations that cluster at the dyad interface and disrupt signal transmission to two coaxial coiled-coils that connect to the effector. Sequence covariation implies wide conservation of structural and mechanistic motifs, as also borne out by comparison to several PAS domains in which mutations leading to disruption of signal transduction consistently map to confined regions broadly equivalent to those identified in YF1. Not only do these data provide insight into general mechanisms of signal transduction, but also they establish concrete means for customized reprogramming of signal receptors.
Performance of Decomposition-Based Many-Objective Algorithms Strongly Depends on Pareto Front Shapes

Recently, a number of high performance many-objective evolutionary algorithms with systematically generated weight vectors have been proposed in the literature. Those algorithms often show surprisingly good performance on widely used DTLZ and WFG test problems. The performance of those algorithms has continued to be improved. The aim of this paper is to show our concern that such a performance improvement race may lead to the overspecialization of developed algorithms for the frequently used many-objective test problems. In this paper, we first explain the DTLZ and WFG test problems. Next, we explain many-objective evolutionary algorithms characterized by the use of systematically generated weight vectors. Then we discuss the relation between the features of the test problems and the search mechanisms of weight vector-based algorithms such as multiobjective evolutionary algorithm based on decomposition (MOEA/D), nondominated sorting genetic algorithm III (NSGA-III), MOEA/dominance and decomposition (MOEA/DD), and $\theta $ -dominance based evolutionary algorithm ( $\theta$ -DEA). Through computational experiments, we demonstrate that a slight change in the problem formulations of DTLZ and WFG deteriorates the performance of those algorithms. After explaining the reason for the performance deterioration, we discuss the necessity of more general test problems and more flexible algorithms.
Relationships among capsular structure, phagocytosis, and mouse virulence in Klebsiella pneumoniae

Klebsiella pneumoniae strains of the K2 capsular serotype are usually highly virulent in mice, which is in contrast to the low virulence of most other serotypes. Here we used a genetic approach to examine the relative contribution of capsule type to the virulence of K. pneumoniae in mice. We used wild-type strains expressing capsular polysaccharide (CPS) serotypes K2 (strain KPA1) and K21a (strains KPB1 and KPC1), which were then used to construct capsule-switched derivatives. The close proximity of the cps gene cluster to selectable his markers made it possible to mobilize the cps genes by conjugation from one serotype (donor) to another (recipient) and to obtain recombinants in which interserotype switching had occurred by reciprocal recombination. Each capsule-switched derivative examined of the KPA and KPC strain backgrounds produced a CPS that was immunologically and structurally identical to that of the donor. Strain background was confirmed by demonstrating restriction fragment length polymorphism patterns identical to those of the respective recipients. The parent strains were then compared with capsule-switched recombinants for phenotypic properties associated with virulence. Clearance from the bloodstreams of mice was rapid in serotype K21a strains of either wild-type or recombinant origin, whereas K2 strains remained viable in the blood during the period examined. These differences appeared to be dependent upon the CPS type but independent of strain background. Binding to macrophages was higher in K21a strains than in those with the K2 capsule and was also independent of the strain background. Both blood clearance and macrophage-binding activities were completely inhibited by yeast mannan, suggesting that they were mediated via the macrophage mannose receptor. The K2 parent strain was highly virulent to mice (50% lethal dose [LD50], 3 x 10(3)), while the K21a parent strains demonstrated low virulence (LD50, > 2 x 10(8)). Interestingly, the virulence of recombinant KPC10(cpsK2), originally of the KPC1(cpsK21a) background, was intermediate (LD50, 4 x 10(5)). In contrast, both cpsK21a recombinants of the originally virulent KPA1 (cpsK2) background became nearly avirulent (LD50, > 2 x 10(8)). Six additional serotypes (K12, K24, K32, K55, K62, and K67) were examined, and all showed a positive correlation between the ability of the Klebsiella serotype to interact with a human mannose receptor, as expressed by Cos I cell recombinants, and the LD50 of the serotype. These results suggest that expression of a capsule which is recognized by the mannose receptor markedly affects the interaction with macrophages and blood clearance. (ABSTRACT TRUNCATED AT 400 WORDS)
RelA/p65 is a molecular target for the immunosuppressive action of protein kinase A.

Stimulation of the protein kinase A (PKA) signalling pathway exerts an inhibitory effect on the proliferation of numerous cells, including T lymphocytes. In CD4+ T helper cells, stimulation of PKA leads to suppression of interleukin 2 (IL‐2) induction, while induction of the genes coding for the lymphokines IL‐4 and IL‐5 is enhanced. We show that the differential effect of PKA activity on induction of the IL‐2 and IL‐4 genes is mediated through their promoters. One major target of the suppressive effect of PKA is the kappa B site in the IL‐2 promoter. A kappa B site is missing in the IL‐4 promoter. Mutations preventing factor binding to the IL‐2 kappa B site result in a loss of PKA‐mediated suppression of IL‐2 promoter activity. Furthermore, activation of the PKA signalling pathway impairs the inducible activity of multiple kappa B sites of the IL‐2 promoter, but not of other factor binding sites. The reduction in activity of kappa B sites in activated and PKA‐stimulated T cells is accompanied by changes in the concentration and DNA binding of Rel/NF‐kappa B factors. Stimulation of the PKA pathway in Jurkat T cells with the PKA activator forskolin leads to an increase in synthesis of c‐Rel and p105/p50, while synthesis of p65/RelA remains unchanged. However, nuclear translocation and DNA binding of p65 is distinctly impaired, probably due to a retarded degradation of I kappa B‐alpha. In a similar way, stimulation of the PKA signalling pathway inhibits nuclear translocation of p65 and generation of nuclear kappa B complexes in peripheral T lymphocytes from murine lymph nodes. These results indicate that PKA‐mediated suppression of NF‐kappa B activity plays an important role in the control of activation of peripheral T lymphocytes.
Fish Oil Treatment for Kidney Transplant Recipients: A Meta-Analysis of Randomized Controlled Trials

Background. Calcineurin inhibitors have adverse effects that contribute to nephrotoxicity and cardiovascular risk profile, and these may be reduced by administration of fish oil. The aim of this review was to assess the benefits and harms of fish oil supplementation in kidney transplant recipients on a calcineurin inhibitor-based immunosuppressive regimen. Methods. The Cochrane Controlled Trials Registry, MEDLINE, and EMBASE were searched for randomized controlled trials of fish oil treatment in kidney transplant recipients on a calcineurin inhibitor-based immunosuppressive regimen. Trials comparing fish oil to both placebo and statins were included. Data were extracted for patient and graft survival, acute rejection, calcineurin inhibitor toxicity, cardiovascular events, adverse effects, compliance, renal function, blood pressure, and lipid profile. Dichotomous outcomes were reported as relative risk and continuous outcome measures as weighted mean differences (WMD), with 95% confidence intervals. Results. Sixteen suitable trials were analyzed. Fish oil treatment was associated with a lower diastolic blood pressure (WMD 4.5 mmHg, P=0.004) and higher high-density lipoprotein (HDL) cholesterol (WMD 0.12 mmol/L, P=0.01) but did not affect the other outcomes. Fishy aftertaste and gastrointestinal upset were common but did not result in significant dropout. Fish oil effects on lipids were not significantly different than low-dose statins. Conclusion. There is insufficient evidence from currently available randomized controlled trials to recommend fish oil therapy to improve renal function, rejection rates, and patient or graft survival. Improvements in HDL cholesterol and diastolic blood pressure were too modest to recommend routine use.
Contribution of molecular typing methods and antifungal susceptibility testing to the study of a candidemia cluster in a burn care unit

We investigated a cluster of cases of Candida septicemia diagnosed in four burn patients. Twenty clinical isolates of Candida albicans and two of Candida parapsilosis, plus eight isolates of C. albicans recovered from nurses' clothes, were analyzed by antifungal susceptibility testing and three genotyping methods (restriction fragment length polymorphism analysis with EcoRI and HinfI, arbitrarily primed PCR, and karyotyping). The high MICs of the azoles for all of the C. albicans isolates tested suggest either a natural resistance of the endogenous flora or the transmission of isolates with acquired resistance. The genotyping methods demonstrated the involvement of four different strains, cross-infections with one C. albicans strain and one C. parapsilosis strain, and identity between some of the strains from the patients and nurses. The origins of the strains remain unclear. Our results show that the use of a combination of at least two different methods such as those used in the present study is recommended for C. albicans typing.