Dose-related effect of methylphenidate on stopping and changing in children with attention-deficit/hyperactivity disorder

PURPOSE: The effect of methylphenidate (MPH) on inhibitory control as assessed by the stop task in children with attention-deficit/hyperactivity disorder (ADHD) could be influenced by task difficulty and may be mediated by attention. SUBJECTS AND METHODS: Fifteen children with ADHD performed the stop and the change task after placebo, 0.5 and 1.0 mg/kg MPH in a within-subject design. RESULTS: Linear-trend analysis showed a similar effect of MPH in both tasks and a stronger effect for inhibitory control than for attention. Furthermore, a correlation was found between blood serum metabolites of norepinephrine and dopamine for attentional measures and inhibitory control measures, respectively. DISCUSSION AND CONCLUSION: In children with ADHD MPH could act primarily on inhibitory control, and is not influenced by task difficulty. Also, attention and inhibitory control could have differential pharmacological profiles.     

Dynamic magnetic resonance imaging for grading pelvic organ prolapse according to the international continence society classification: Which line should be used?

AIMS: To assess and compare the reliability of dynamic MRI to quantify pelvic organ prolapse (POP) according to the International Continence Society (ICS) using two different reference lines, and to determine which line gives the best concordance with clinical examination. METHODS: Forty-seven patients with genital prolapse underwent physical examination and dynamic MRI. Five nulliparous, symptom-free female volunteers underwent dynamic MRI as control subjects. Two distinct observers performed the MRI measurements of POP according to the ICS using two distinct reference lines: the mid-pubic line and a new one, the perineal line that provides a better match with the hymen plane. Measurements were repeated twice according to each line. The intra-class coefficient was used to estimate intra-observer and inter-observer reliability; the Altman and Bland plot was used to assess the agreement between MRI and clinical measurements. RESULTS: The intra-observer and inter-observer reliability of MRI measurements were in general excellent. Intra-class coefficients were better for the mid-pubic line than the perineal line. Although the MRI measurements correlate significantly with the physical measurements, the Altman and Bland plot shows an unacceptable magnitude of discrepancy between clinical and MRI examinations. CONCLUSIONS: Although dynamic MRI shows excellent inter- and intra-observer reliability, its agreement with clinical examination is poor whatever the line used.     

Comparison between the C-leg microprocessor-controlled prosthetic knee and non-microprocessor control prosthetic knees: a preliminary study of energy expenditure, obstacle course performance, and quality of life survey

This study investigated energy expenditure and obstacle course negotiation between the C-leg and various non-microprocessor control (NMC) prosthetic knees and compared a quality of life survey (SF-36v2) of use of the C-leg to national norms. Thirteen subjects with unilateral limb loss (12 with trans-femoral and one with a knee disarticulation amputation) participated in the study. The mean age was 46 years, range 30-75. Energy expenditure using both the NMC and C-leg prostheses was measured at self-selected typical and fast walking paces on a motorized treadmill. Subjects were also asked to walk through a standardized walking obstacle course carrying a 4.5 kg (10 lb) basket and with hands free. Finally, the SF-36v2 was completed for subjects while using the C-leg. Statistically significant differences were found in oxygen consumption between prostheses at both typical and fast paces with the C-leg showing decreased values. Use of the C-leg resulted in a statistically significant decrease in the number of steps and time to complete the obstacle course. Scores on a quality of life index for subjects using the C-leg were above the mean for norms for limitation in the use of an arm or leg, equal to the mean for the general United States population for the physical component score and were above this mean for the mental component score. Based on oxygen consumption and obstacle course findings, the C-leg when compared to the NMC prostheses may provide increased functional mobility and ease of performance in the home and community environment. Questionnaire results suggest a minimal quality of life impairment when using a C-leg for this cohort of individuals with amputation.     

Reducing Behavior Problems Among Students with Autism Spectrum Disorder: Coaching Teachers in a Mixed-Reality Setting

Most approaches aiming to reduce behavior problems among youth with Autism Spectrum Disorder (ASD) focus on individual students; however, school personnel also need professional development to better support students. This study targeted teachers’ skill development to promote positive outcomes for students with ASD. The sample included 19 teachers in two non-public special education settings serving students with moderate to severe ASD. Participating teachers received professional development and coaching in classroom management, with guided practice in a mixed-reality simulator. Repeated-measures ANOVAs examining externally-conducted classroom observations revealed statistically significant improvements in teacher management and student behavior over time. Findings suggest that coaching and guided practice in a mixed-reality simulator is perceived as acceptable and may reduce behavior problems among students with ASD.     

Induction of Donor-Specific Allograft Tolerance by Short-Term Treatment with LF15-0195 After Transplantation. Evidence for a Direct Effect on T-Cell Differentiation

A 20-day treatment with LF15-0195, a deoxyspergualine analog, induced long-term heart allograft survival in the rat without signs of chronic rejection. LF15-0195-treated recipients did not develop an anti-donor alloantibody response. Analysis of graft-infiltrating cells, IL10, TNFalpha, IFNgamma mRNA and iNOS protein expression in allografts, 5 days after transplantation, showed that they were markedly decreased in allografts from LF15-0195-treated recipients compared with allografts from untreated recipients. Surprisingly, spleen T cells from LF15-0195 recipients, 5days after grafting, were able to proliferate strongly in vitro, when stimulated with donor cells, but had reduced mRNA expression for IFNy compared with spleen T cells from untreated graft recipients. Furthermore, when T cells from naive animals were stimulated in vitro, using anti-CD3 and anti-CD28, LF15-0195 also increased T-cell proliferation in a dose-dependent fashion: however, these cells expressed less of the Th1 -related cytokines, IFNgamma and IL2, compared with untreated cells, suggesting that LF15-0195 could act on T-cell differentiation. In conclusion, we show here that a short-term treatment with LF15-0195 induced long-term allograft tolerance, decreasing the in situ anti-donor response, and we illustrate evidence for the development of regulatory mechanisms.     

Sweet and simple as syrup: A review and guidance for use of novel antihyperglycemic agents for post-transplant diabetes mellitus and type 2 diabetes mellitus after kidney transplantation

Uncontrolled type 2 diabetes mellitus (T2DM) and post-transplant diabetes mellitus (PTDM) increase morbidity and mortality after kidney transplantation. Conventional strategies for diabetes management in this population include metformin, sulfonylureas, meglitinides and insulin. Limitations with these agents, as well as promising new antihyperglycemic agents, create a need and opportunity to explore additional options for transplant diabetes pharmacotherapy. Novel agents including sodium glucose co-transporter 2 inhibitors (SGLT2i), glucagon-like peptide-1 receptor agonists (GLP1RA), and dipeptidyl peptidase IV inhibitors (DPP4i) demonstrate great promise for T2DM management in the non-transplant population. Moreover, many of these agents possess renoprotective, cardiovascular, and/or weight loss benefits in addition to improved glucose control while having reduced risk of hypoglycemia compared with certain other conventional agents. This comprehensive review examines available literature evaluating the use of novel antihyperglycemic agents in kidney transplant recipients (KTR) with T2DM or PTDM. Formal grading of recommendations assessment, development, and evaluation (GRADE) system recommendations are provided to guide incorporation of these agents into post-transplant care. Available literature was evaluated to address the clinical questions of which agents provide greatest short- and long-term benefits, timing of novel antihyperglycemic therapy initiation after transplant, monitoring parameters for these antihyperglycemic agents, and concomitant antihyperglycemic agent and immunosuppression regimen management. Current experience with novel antihyperglycemic agents is primarily limited to single-center retrospective studies and case series. With ongoing use and increasing comfort, further and more robust research promises greater understanding of the role of these agents and place in therapy for kidney transplant recipients.     

Hypoxia and HIF-1α expression in the epiphyseal cartilage following ischemic injury to the immature femoral head

HIF-1α has been shown to be a central mediator of cellular response to hypoxia. The role it plays after ischemic injury to the immature femoral head is unknown. The purpose of this study was to determine the region of the femoral head affected by hypoxia following ischemic injury to the immature femoral head and to determine the site of HIF-1α activation and revascularization. We hypothesize that the epiphyseal cartilage, rather than the bony epiphysis, is the site of HIF-1α activation following ischemic osteonecrosis and that the epiphyseal cartilage plays an important role in the revascularization process.Materials and methodsFemoral head osteonecrosis was surgically induced in 56 immature pigs. Hypoxyprobe staining, cell viability assay, HIF-1α western blot, RT-qPCR of HIF-1α, VEGF, VEGFR2, and PECAM, and micro-CT assessments of microfil-infused femoral heads were performed.ResultsSevere hypoxia was present in the bony epiphysis and the lower part of the epiphyseal cartilage following ischemia. In the bony epiphysis, extensive cell death and tissue necrosis was observed with degradation of proteins and RNAs which precluded further analysis. In the epiphyseal cartilage, the loss of cell viability was limited to its deep layer with the remainder of the cartilage remaining viable. Furthermore, the cartilage from the ischemic side showed a significant increase in HIF-1α protein level and HIF-1α expression. VEGF expression in the cartilage was dramatically and significantly increased at 24 h, 2 and 4 weeks (p < 0.05 for all) with 5 to 10 fold increase being observed on the ischemic side compared to the normal side. PECAM and VEGFR2 expressions in the cartilage were both significantly decreased at 24 h but returned to the normal levels by 2 and 4 weeks, respectively. Micro-CT showed revascularization of the cartilage on the ischemic side with the vessel volume/total volume equaling the normal side by 4 weeks.ConclusionsAcute ischemic injury to the immature femoral head induced severe hypoxia and cell death in the bony epiphysis and the deep layer of the epiphyseal cartilage. Viable chondrocytes in the superficial layer of the epiphyseal cartilage showed HIF-1α activation and VEGF upregulation with subsequent revascularization occurring in the cartilage.     

Minimization of maintenance immunosuppressive therapy after renal transplantation comparing cyclosporine A/azathioprine or cyclosporine A/mycophenolate mofetil bitherapy to cyclosporine A monotherapy: a 10‐year postrandomization follow‐up study

Long‐term outcomes in renal transplant recipients withdrawn from steroid and submitted to further minimization of immunosuppressive regimen after 1 year are lacking. In this multicenter study, 204 low immunological risk kidney transplant recipients were randomized 14.2 ± 3.7 months post‐transplantation to receive either cyclosporine A (CsA) + azathioprine (AZA; n = 53), CsA + mycophenolate mofetil (MMF; n = 53), or CsA monotherapy (n = 98). At 3 years postrandomization, the occurrence of biopsy for graft dysfunction was similar in bitherapy and monotherapy groups (21/106 vs. 26/98; P = 0.25). At 10 years postrandomization, patients’ survival was 100%, 94.2%, and 95.8% (P = 0.25), and death‐censored graft survival was 94.9%, 94.7%, and 95.2% (P = 0.34) in AZA, MMF, and CsA groups, respectively. Mean estimated glomerular filtration rate was 70.4 ± 31.1, 60.1 ± 22.2, and 60.1 ± 19.0 ml/min/1.73 m², respectively (P = 0.16). The incidence of biopsy‐proven acute rejection was 1.4%/year in the whole cohort. None of the patients developed polyomavirus‐associated nephropathy. The main cause of graft loss (n = 12) was chronic antibody‐mediated rejection (n = 6). De novo donor‐specific antibodies were detected in 13% of AZA‐, 21% of MMF‐, and 14% of CsA‐treated patients (P = 0.29). CsA monotherapy after 1 year is safe and associated with prolonged graft survival in well‐selected renal transplant recipient ( ClinicalTrials.gov number: 980654).