BackgroundHemodialysis is associated with a high symptom burden that impairs health-related quality of life and functional status. Effective symptom management is a priority for individuals receiving hemodialysis. Aerobic exercise may be an effective, nonpharmacologic treatment for specific hemodialysis-related symptoms. This systematic review investigated the effect of aerobic exercise on hemodialysis-related symptoms in adults with kidney failure undergoing maintenance hemodialysis.Design, setting, participants, & measurementsWe searched MEDLINE, PubMed, Cochrane CENTRAL, CINAHL, PsycINFO, SPORTDiscus, EMBASE, PEDro, and Scopus databases from 1960 or inception until April 15, 2020 for randomized controlled trials investigating the effect of aerobic exercise on hemodialysis-related symptoms, identified as prespecified primary or secondary outcomes, as compared with controls in adults on maintenance hemodialysis. We identified restless legs syndrome as the primary outcome.ResultsOf 3048 studies identified, 15 randomized controlled trials met the eligibility criteria. These studies investigated the effect of aerobic exercise on restless legs syndrome (two studies), sleep disturbance (four studies), anxiety (four studies), depression (nine studies), muscle cramping (one study), and fatigue (one study). Exercise interventions were intradialytic in ten studies and outside of hemodialysis in five studies. Heterogenous interventions and outcomes and moderate to high risk of bias precluded meta-analysis for most symptoms. Aerobic exercise demonstrated improvement in symptoms of restless legs syndrome, muscle cramping, and fatigue, as compared with nonexercise controls. Meta-analysis of depressive symptoms in studies using the Beck Depression Inventory demonstrated a greater reduction in Beck Depression Inventory score with exercise as compared with control (mean difference −7.57; 95% confidence interval, −8.25 to −6.89).ConclusionsOur review suggests that in adults on maintenance hemodialysis, aerobic exercise improves several hemodialysis-related symptoms, including restless legs syndrome, symptoms of depression, muscle cramping, and fatigue. However, the use of validated outcome measures with demonstrated reliability and responsiveness in more diverse hemodialysis populations is required to fully characterize the effect of this intervention.Clinical Trial registry name and registration number:PROSPERO #CRD42017056658

Eukaryotic gene expression is controlled at multiple levels, including gene transcription and protein translation initiation. One molecule with key roles in both regulatory mechanisms is methyl CpG binding protein 2 (MeCP2). MECP2 gain- and loss-of-function mutations lead to Rett Syndrome and MECP2 Duplication Syndrome, respectively. To study MECP2 gain-of-function, we generated stably transduced human brain cells using lentiviral vectors for both MECP2E1 and MECP2E2 isoforms. Stable overexpression was confirmed by Western blot and immunofluorescence. We assessed the impact of MeCP2E1-E2 gain-of-function on the MeCP2 homeostasis regulatory network (MECP2E1/E2-BDNF/BDNF-miR-132), mTOR-AKT signaling, ribosome biogenesis, markers of chromatin structure, and protein translation initiation. We observed that combined co-transduction of MeCP2 isoforms led to protein degradation of MeCP2E1. Proteosome inhibition by MG132 treatment recovered MeCP2E1 protein within an hour, suggesting its induced degradation through the proteosome pathway. No significant change was detected for translation initiation factors as a result of MeCP2E1, MeCP2E2, or combined overexpression of both isoforms. In contrast, analysis of human Rett Syndrome brains tissues compared with controls indicated impaired protein translation initiation, suggesting that such mechanisms may have differential sensitivity to MECP2 gain- and loss-of-function. Collectively, our results provide further insight towards the dose-dependent functional role of MeCP2 isoforms in the human brain.

Context: Children with critical CHD are at risk for neurodevelopmental impairments, including delays in expressive and receptive language development. However, no study has synthesised the literature regarding language abilities in children with this condition. Objective: We summarised the literature regarding expressive and receptive language in preschool children with critical CHD. Data sources: MEDLINE, Embase, Scopus, Child Development and Adolescent Studies, ERIC, PsycINFO, and CINAHL. Study selection: We included studies published between January, 1990 and 1 July, 2021, focused on children aged ≤5 years with critical CHD requiring a complex cardiac procedure at age <1 year. Language ability was documented using standardised, validated tools assessing both expressive and receptive language outcomes. Data extraction: Data (study, patient and language characteristics, and results) were extracted by two reviewers. Results: Seventeen studies were included. Among children 2–5 years old with critical CHD, there were statistically significant deficits in overall (standardised mean difference: –0.46; 95 % confidence interval: –0.56, –0.35), expressive (standardised mean difference: –0.45;95 % confidence interval: –0.54, –0.37), and receptive (standardised mean difference: –0.32; 95 % confidence interval: –0.40, –0.23) language compared to normative data. Results reported as medians were similar to meta-analysis findings. Subgroup analysis showed that children with univentricular physiology had lower language scores than children with biventricular physiology. Conclusions: Preschool children with critical CHD had statistically significantly lower language outcomes compared to expected population norms. Healthcare professionals should test early and often for language deficits, referring to individually tailored supports.

Background: Cardiac Implantable Electronic Devices (CIED) include pulse generators and leads. In some implanting centres, it is common practice to combine devices with leads from different companies. Case series have reported episodic high-impedance changes in Boston Scientific CIEDs with competitor leads. We investigated the incidence of high-impedance abnormalities in matched vs. mismatched Boston Scientific CIEDs. Methods: Retrospective chart review identified all consecutive Boston Scientific Accolade pacemakers and Autogen implantable cardioverter defibrillators (ICD) implanted between January 2017 and June 2019 at a Canadian tertiary care centre. The primary outcome was the occurrence of transient, high-impedance changes which resulted in a switch to unipolar pacing / sensing in the absence of any other identifiable lead issue. Fisher exact tests (two-tailed, α = 0.05) were used to compare the incidence of outcomes in matched vs. mismatched systems. Results: 564 Boston Scientific CIEDs were identified associated with 969 individual leads. The primary outcome occurred with 22 leads (21 Medtronic and 1 Abbott), associated with occasional pacing inhibition, syncope, and/or early surgical revision. Mismatched systems were significantly associated with CIED malfunction compared to matched systems (3.4% vs. 0%, P = 0.0001). Median time from implant to unipolar safety switch was 19.3 months. Median follow-up time was 21.6 months. Conclusion: Use of mismatched leads with a Boston Scientific Accolade or Autogen device was associated with increased system malfunction and adverse clinical outcomes. Awareness of this interaction can allow for institution of appropriate programming remedies and may increase scrutiny of the use of mismatched CIED systems.

Background Cardiac Implantable Electronic Devices (CIED) include pulse generators and leads. In some implanting centers, it is a common practice to combine devices with leads from different companies. Case series have reported episodic high‐impedance changes in Boston Scientific CIEDs with competitor leads. We investigated the incidence of high‐impedance abnormalities in matched versus mismatched Boston Scientific Accolade pacemakers. Methods A retrospective chart review identified all consecutive Boston Scientific Accolade pacemakers implanted between January 2017 and June 2019 at a Canadian tertiary care center. The primary outcome was the occurrence of transient, high‐impedance changes which resulted in a switch to unipolar pacing/sensing in the absence of any other identifiable lead issue. Fisher exact tests (two‐tailed, α = .05) were used to compare the incidence of outcomes in matched versus mismatched systems. Results 514 Boston Scientific Accolade pacemakers were associated with 882 individual leads. The primary outcome occurred with 21 leads (20 Medtronic and 1 Abbott), associated with occasional pacing inhibition, presyncope, and/or early surgical revision. Mismatched lead‐device pairs were significantly associated with CIED malfunction compared to matched lead‐device pairs (3.3% vs. 0%, p = .0019). The median time from implant to unipolar safety switch was 12.4 months. The median follow‐up time was 21.6 months. Conclusion Use of mismatched leads with a Boston Scientific Accolade device was associated with an increased risk of undesirable changes in sensing polarity with occasional inappropriate pacing inhibition. Awareness of this interaction can allow for the institution of appropriate programming remedies and may increase scrutiny of the use of mismatched CIED systems.