Miracle-dz/UniFAR-FTUs huggingface dataset:
A Comparison Of Tacrolimus (fk506) And Cyclosporine For Immunosuppression After Cadaveric Renal Transplantation1

Background. Tacrolimus (FK506), a macrolide molecule that potently inhibits the expression of interleukin 2 by T lymphocytes, represents a potential major advance in the management of rejection following solid-organ transplantation. This randomized, open-label study compared the efficacy and safety of tacrolimus-based versus cyclosporine-based immunosuppression in patients receiving cadaveric kidney transplants. Methods. A total of 412 patients were randomized to tacrolimus (n=205) or cyclosporine (n=207) after cadaveric renal transplantation and were followed for 1 year for patient and graft survival and the incidence of acute rejection. Results. One-year patient survival rates were 95.6% for tacrolimus and 96.6% for cyclosporine (P=0.576). Corresponding 1-year graft survival rates were 91.2% and 87.9% (P=0.289). There was a significant reduction in the incidence of biopsy-confirmed acute rejection in the tacrolimus group (30.7%) compared with the cyclosporine group (46.4%, P=0.001), which was confirmed by blinded review, and in the use of antilymphocyte therapy for rejection (10.7% and 25.1%, respectively; P<0.001). Impaired renal function, gastrointestinal disorders, and neurological complications were commonly reported in both treatment groups, but tremor and paresthesia were more frequent in the tacrolimus group. The incidence of posttransplant diabetes mellitus was 19.9% in the tacrolimus group and 4.0% in the cyclosporine group (P<0.001), and was reversible in some patients. Conclusions. Tacrolimus is more effective than cyclosporine in preventing acute rejection in cadaveric renal allograft recipients, and significantly reduces the use of antilymphocyte antibody preparations. Tacrolimus was associated with a higher incidence of neurologic events, which were rarely treatment limiting, and with posttransplant diabetes mellitus, which was reversible in some patients.
Hip range of motion during daily activities in patients with posterior pelvic tilt from supine to standing position

In most patients with hip disorders, the anterior pelvic plane (APP) sagittal tilt does not change from supine to standing position. However, in some patients, APP sagittal tilt changes more than 10° posteriorly from supine to standing position. The purpose of this study was to both examine APP sagittal tilt and investigate the hip flexion and extension range of motion (ROM) required during daily activities in these atypical patients. Patient‐specific 4‐dimensional (4D) motion analysis was performed for 50 hips from 44 patients who had undergone total hip arthroplasty. All patients divided into two categories, such as atypical patients for whom the pelvis tilted more than 10° posteriorly from supine to standing position preoperatively (19 hips from 18 patients) and the remaining typical patients (31 hips from 26 patients). The required hip flexion and extension angles did not differ significantly between atypical patients and typical patients. In conclusion, the hip flexion ROM during deep bending activities and hip extension ROM during extension activities required in those atypical patients with pelvic tilt more than 10° backward from supine to standing position did not shift in the direction of extension. © 2015 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 33:542–547, 2015.
Palliative care and management principles in older patients with advanced chronic obstructive pulmonary disease

Advanced chronic obstructive pulmonary disease (COPD) patients are likely to develop comorbidities that may contribute to a substantial burden of symptoms such as intolerable dyspnea, fatigue and poor-health status. Evidence from the available literature suggests that advanced COPD patients are less likely to receive palliative care and/or supportive care compared with cancer patients. Factors that contribute to this disparity are multifactorial, including diagnostic uncertainty of when to provide palliative care, patients’ unwillingness to discuss advanced care planning with their general practitioners, lack of appropriate guidelines regarding when to refer patients to palliative care and lack of adequate resources. A few unblinded studies of palliative-care provision that included advanced COPD patients with other life-threatening diseases demonstrated some benefits in reducing healthcare utilization, improving quality of life and greater patient and caregiver satisfaction with the service. Therefore, f.
The role of complex clinical scenarios in the failure of modular components following revision total knee arthroplasty: A finite element study

Modular prostheses are increasingly applied in complex revision knee arthroplasty scenarios due to the greater intraoperative flexibility they provide to the surgeon, for example, accurate placement of stem in canal while maintaining a good fit distally for complex femoral geometry. However, growing evidence indicates that these modular devices often fail at the stem junction. Modular prostheses are generally applied to provide enhanced fixation in poor quality bone or in the presence of condylar defects. From the literature, it is unclear which of these patient scenarios contribute the most to modular component failure. The present study uses finite element (FE) models to answer this question. The findings of this study indicate that the most significant increase in stem junction stress occurs in the presence of large condylar defects. However, taking into account standard clinical practice (large F3 defects typically result in distal femoral replacement), the most significant factor is then found to be compromised bone quality, these findings are particularly evident at higher flexion angles. Based on the findings of this study, it can be concluded that patients with large femoral defects or severely compromised bone quality are particularly vulnerable to implant failure when a modular approach is adopted. © 2015 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 33:1134–1141, 2015.
Combination therapy with intra‐articular injection of mesenchymal stem cells and articulated joint distraction for repair of a chronic osteochondral defect in the rabbit

The present study investigated intra‐articular injection of bone‐marrow‐derived mesenchymal stem cells (MSCs) combined with articulated joint distraction as treatment for osteochondral defects. Large osteochondral defects were created in the weight‐bearing area of the medial femoral condyle in rabbit knees. Four weeks after defect creation, rabbits were divided into six groups: control group, MSC group, distraction group, distraction + MSC group, temporary distraction group, and temporary distraction + MSC group. Groups with MSC received intra‐articular injection of MSCs. Groups with distraction underwent articulated distraction arthroplasty. Groups with temporary distraction discontinued the distraction after 4 weeks. The rabbits were euthanized at 4, 8, and 12 weeks after treatment except temporary distraction groups which were euthanized at only 12 weeks. Histological scores in the distraction + MSC group were significantly better than in the control, MSC group or distraction group at 4 and 8 weeks, but showed no further improvement. At 12 weeks, the temporary distraction + MSC group showed the best results, demonstrating hyaline cartilage repair with regeneration of the osteochondral junction. In conclusion, joint distraction with intra‐articular injection of MSCs promotes early cartilage repair, and compressive loading of the repair tissue after temporary distraction stimulates articular cartilage regeneration. © 2015 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 33:1466–1473, 2015.
Stent Graft Repair of Thoracic Aortic Pathology

Stent-graft repair of thoracic aortic pathology has progressed to phase II clinical trials of commercially made devices. The latter represent substantial improvements from previously employed homemade constructs. Preliminary experience indicates that stent-graft repair for anatomically suitable degenerative aneurysms will present an effective and less morbid approach when compared to open repair. Prospective trials of stent-graft repair for the other lesions-in-particular acute distal aortic dissections—will be required before its ultimate role is defined.
Surgical Treatment of Locally Advanced Rectal Cancer

Aims: The results of surgical treatment of locally advanced rectal cancer with special regard to multivisceral resections and preoperative radiotherapy should be analyzed. Methods: From 10/86 until 12/95, 40 patients with preoperatively assessed T4 stage rectal cancer were treated in our department whose data were evaluated retrospectively. Results: Apart from 10 nonresecting procedures we performed 30 resections in which the mortality rate was 7%. In 50% of these patients a multivisceral resection was conducted. A R0 situation could be achieved in 70%. But only in 53% the operation was carried out with curative approach due to distant metastasis. After extended resections more frequent urological complications resulted in prolonged hospitalization. Survival time was markedly longer in patients without tumor residuals or metastasis. Following preoperative radiotherapy a higher number in tumor free patients and better prognosis was noticed. Conclusions: In accordance to the literature it is suggested to submit patients with T4-stage rectal cancer to preoperative radiation to improve the overall outcome.
Auditory Brainstem Response: Its Place in Infant Audiological Evaluations

A hotly debated issue among pediatric audiologists today revolves around the value of the auditory brainstem response (ABR) as an effective approach to the audiological assessment of neonates and young infants. Healthy skepticism and continued reliance on traditional behavioral procedures are due to disappointment in past "objective" methods, frequently heralded as the solution to all audiological problems. Initial enthusiasm for cardiovascular or respiratory responses, or the " la te" auditory evoked potentials utilized in the 60's, was rapidly tempered by equivocal findings and methodological problems occurring in precisely those patients most in need of assessment: infants and multihandicapped children (Gerber, 1977; Picton, 1977). Therefore, many clinicians are hesitant to abandon infant behavioral protocols they have spent years developing. On the other hand, while our skills in evaluating infants have improved, the neonate at risk and needing assessment today has unfortunately changed. Consequently, behavioral test protocols effective in a term neonate will fall short when confronted with a premature "graduate"
Differences in the vascular tree of the femoral trochlear growth cartilage at osteochondrosis‐susceptible sites in foals revealed by SWI 3T MRI

Focal ischemic chondronecrosis of epiphyseal growth cartilage (EGC) during endochondral ossification is believed to be a key early event on the pathway to osteochondrosis (OC) in both animals and humans. The lateral ridge of the equine trochlea is a site where severe osteochondritis dissecans lesions frequently arise and is a model for the study of naturally occurring disease. Non‐invasive imaging to investigate EGC vascularity may help elucidate why focal ischemia occurs. 3T MRI susceptibility‐weighted imaging (SWI) of femoral trochlea of OC predisposed (n = 10) and control (n = 6) day‐old foals, with minimal joint loading after birth, was performed. SWI and 3D images revealed the EGC vascular architecture without a contrast agent, and matched histologic observations. No vascular lesions were identified. There was no difference in the vascular density and architecture between control and OC specimens, but a striking difference in vascular pattern was seen at the OC‐predilected site in the lateral ridge of the trochlea in all specimens, when compared to the medial ridge of the trochlea, where OC lesions are rarely observed. This site was less ossified with more perichondrial vessels not yet bridging with the subchondral bone. Furthermore, the mean vascular density of all specimens was significantly higher at this site. We speculate that joint morphology and focal internal trauma on this site with a unique vascular architecture may trigger ischemic events at this site. SWI permitted visualization of EGC in young foals with a clinical 3T MRI and paves the way for non‐destructive longitudinal studies to improve understanding of OC in all species. © 2016 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 34:1539–1546, 2016.
Risk architecture of schizophrenia: the role of epigenetics

Purpose of review To systematize existing data and review new findings on the cause of schizophrenia and outline an improved mixed model of schizophrenia risk. Recent findings Multiple and variable genetic and environmental factors interact to influence the risk of schizophrenia. Both rare variants with large effect and common variants with small effect contribute to genetic risk of schizophrenia, with no indication for differential impact on its clinical features. Accumulating evidence supports a genetic architecture of schizophrenia with multiple scenarios, including additive polygenic, heterogeneity, and mixed polygenic-heterogeneity. The epigenetic mechanisms that mediate gene–environment (GxE) interactions provide a framework to incorporate environmental factors into models of schizophrenia risk. Environmental pathogens with small effect on risk have robust effects in the context of family history of schizophrenia. Hence, genetic risk for schizophrenia may be expressed in part as sensitivity to environmental factors. Summary We propose an improved mixed model of schizophrenia risk in which abnormal epigenetic states with large effects are superimposed on a polygenic liability to schizophrenia. This scenario can account for GxE interactions and shared family environment, which in many cases are not explained by a single structural variant of large effect superimposed on polygenes (the traditional mixed model).
Exercise type and intensity in relation to coronary heart disease in men

ContextStudies have shown an inverse relationship between exercise and risk of coronary heart disease (CHD), but data on type and intensity are sparse.ObjectiveTo assess the amount, type, and intensity of physical activity in relation to risk of CHD among men.Design, Setting, and ParticipantsA cohort of 44 452 US men enrolled in the Health Professionals' Follow-up Study, followed up at 2-year intervals from 1986 through January 31, 1998, to assess potential CHD risk factors, identify newly diagnosed cases of CHD, and assess levels of leisure-time physical activity.Main Outcome MeasureIncident nonfatal myocardial infarction or fatal CHD occurring during the follow-up period.ResultsDuring 475 755 person-years, we documented 1700 new cases of CHD. Total physical activity, running, weight training, and rowing were each inversely associated with risk of CHD. The RRs (95% confidence intervals [CIs]) corresponding to quintiles of metabolic equivalent tasks (METs) for total physical activity adjusted for age, smoking, and other cardiovascular risk factors were 1.0, 0.90 (0.78-1.04), 0.87 (0.75-1.00), 0.83 (0.71-0.96), and 0.70 (0.59-0.82) (P<.001 for trend). Men who ran for an hour or more per week had a 42% risk reduction (RR, 0.58; 95% CI, 0.44-0.77) compared with men who did not run (P<.001 for trend). Men who trained with weights for 30 minutes or more per week had a 23% risk reduction (RR, 0.77; 95% CI, 0.61-0.98) compared with men who did not train with weights (P = .03 for trend). Rowing for 1 hour or more per week was associated with an 18% risk reduction (RR, 0.82; 05% CI, 0.68-0.99). Average exercise intensity was associated with reduced CHD risk independent of the total volume of physical activity. The RRs (95% CIs) corresponding to moderate (4-6 METs) and high (6-12 METs) activity intensities were 0.94 (0.83-1.04) and 0.83 (0.72-0.97) compared with low activity intensity (<4 METs) (P = .02 for trend). A half-hour per day or more of brisk walking was associated with an 18% risk reduction (RR, 0.82; 95% CI, 0.67-1.00). Walking pace was associated with reduced CHD risk independent of the number of walking hours.ConclusionsTotal physical activity, running, weight training, and walking were each associated with reduced CHD risk. Average exercise intensity was associated with reduced risk independent of the number of MET-hours spent in physical activity.
Dynamic Connectivity at Rest Predicts Attention Task Performance

Consistent spatial patterns of coherent activity, representing large-scale networks, have been reliably identified in multiple populations. Most often, these studies have examined "stationary" connectivity. However, there is a growing recognition that there is a wealth of information in the time-varying dynamics of networks which has neural underpinnings, which changes with age and disease and that supports behavior. Using factor analysis of overlapping sliding windows across 25 participants with Parkinson disease (PD) and 21 controls (ages 41-86), we identify factors describing the covarying correlations of regions (dynamic connectivity) within attention networks and the default mode network, during two baseline resting-state and task runs. Cortical regions that support attention networks are affected early in PD, motivating the potential utility of dynamic connectivity as a sensitive way to characterize physiological disruption to these networks. We show that measures of dynamic connectivity are more reliable than comparable measures of stationary connectivity. Factors in the dorsal attention network (DAN) and fronto-parietal task control network, obtained at rest, are consistently related to the alerting and orienting reaction time effects in the subsequent Attention Network Task. In addition, the same relationship between the same DAN factor and the alerting effect was present during tasks. Although reliable, dynamic connectivity was not invariant, and changes between factor scores across sessions were related to changes in accuracy. In summary, patterns of time-varying correlations among nodes in an intrinsic network have a stability that has functional relevance.
The role of C-reactive protein in the resolution of bacterial infection

C-reactive protein is an acute phase protein in man and an important component of the innate immune system. C-reactive protein activates the classical pathway of complement, which is one of its main mechanisms in providing host defense. It has recently been recognized that C-reactive protein interacts with the cells of the immune system by binding to Fc gamma receptors. It may thus bridge the gap between innate and adaptive immunity and provide an early, effective antibacterial response. Furthermore, as it protects against the damaging inflammatory response to lipopolysaccharide and cytokines, it may prevent the lethal side-effects of bacterial products. The recent identification of the interaction of C-reactive protein with Fc gamma receptors will lead to an enhanced understanding of C-reactive protein and its role in both the innate and acquired immune systems.
Staphylococcal enterotoxin C2 expedites bone consolidation in distraction osteogenesis

Distraction osteogenesis (DO) technique could be used to manage large‐size bone defect successfully, but DO process usually requires long duration of bone consolidation. Innovative approaches for augmenting bone consolidation are of great need. Staphylococcal enterotoxin C2 (SEC2) has been found to suppress osteoclastogenesis of mesenchymal stem cells in vitro. In this study, we investigated the effect of SEC2 on proliferation and osteogenic differentiation of rat bone marrow derived mesenchymal stem cells (rBMSCs). Further, we locally administrated SEC2 (10 ng/ml) or PBS into the distraction gap in Sprague–Dawley male rat DO model every 3 days till termination at 3 and 6 weeks. The regenerates were subjected to X‐rays, micro‐computed tomography, mechanical testing, histology, and immunohischemistry examinations to assess new bone quality. SEC2 had no effect on cell viability. The calcium deposition was remarkably increased and osteogenic marker genes were significantly up‐regulated in rBMSCs treated with SEC2. In rat DO model, SEC2 group had higher bone volume/total tissue volume in the regenerates. At 6 weeks, mechanical properties were significantly higher in SEC2‐treated tibiae comparing to the control group. Histological analysis confirmed that the new bone had improved quality in SEC2 treated group, where the osteocalcin and osterix expression in the regenerates was up‐regulated, indicating faster bone formation. The current study demonstrated that SEC2 local injection promotes osteogenesis and enhanced bone consolidation in DO. The findings support application of SEC2 as a potential novel strategy to expedite bone consolidation in patients undergoing DO treatment. © 2016 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 35:1215–1225, 2017.
Familial adenomatous polyposis coli: Report of a rare entity

We report a sporadic case of a familial adenomatous polyposis coli (FAP) in a 25-year-old male who came with no family history of the same. FAP is the most common inherited adenomatous polyposis syndrome. Because of its rarity, the incidence in a developing country like ours is unknown. It is characterized by more than 100 adenomatous polyps and if left untreated carries a 100% risk of progression to colorectal cancer by the fourth decade. The early recognition and characterization of the polyposis syndrome is vital since early intervention and surgery will help in prevention against the development of invasive colorectal cancer.
Fracture healing physiology and the quest for therapies for delayed healing and nonunion

Delayed healing and nonunion of fractures represent enormous burdens to patients and healthcare systems. There are currently no approved pharmacological agents for the treatment of established nonunions, or for the acceleration of fracture healing, and no pharmacological agents are approved for promoting the healing of closed fractures. Yet several pharmacologic agents have the potential to enhance some aspects of fracture healing. In preclinical studies, various agents working across a broad spectrum of molecular pathways can produce larger, denser and stronger fracture calluses. However, untreated control animals in most of these studies also demonstrate robust structural and biomechanical healing, leaving unclear how these interventions might alter the healing of recalcitrant fractures in humans. This review describes the physiology of fracture healing, with a focus on aspects of natural repair that may be pharmacologically augmented to prevent or treat delayed or nonunion fractures (collectively referred to as DNFs). The agents covered in this review include recombinant BMPs, PTH/PTHrP receptor agonists, activators of Wnt/β‐catenin signaling, and recombinant FGF‐2. Agents from these therapeutic classes have undergone extensive preclinical testing and progressed to clinical fracture healing trials. Each can promote bone formation, which is important for the stability of bridged calluses, and some but not all can also promote cartilage formation, which may be critical for the initial bridging and subsequent stabilization of fractures. Appropriately timed stimulation of chondrogenesis and osteogenesis in the fracture callus may be a more effective approach for preventing or treating DNFs compared with stimulation of osteogenesis alone. © 2016 The Authors. Journal of Orthopaedic Research published by Wiley Periodicals, Inc. on behalf of the Orthopaedic Research Society. J Orthop Res 35:213–223, 2017.