Proteomic analysis of heart failure hospitalization among patients with chronic kidney disease: The Heart and Soul Study.

BACKGROUND:Patients with chronic kidney disease (CKD) are at increased risk for heart failure (HF). We aimed to investigate differences in proteins associated with HF hospitalizations among patients with and without CKD in the Heart and Soul Study. METHODS AND RESULTS:We measured 1068 unique plasma proteins from baseline samples of 974 participants in The Heart and Soul Study who were followed for HF hospitalization over a median of 7 years. We sequentially applied forest regression and Cox survival analyses to select prognostic proteins. Among participants with CKD, four proteins were associated with HF at Bonferroni-level significance (p<2.5x10(-4)): Angiopoietin-2 (HR[95%CI] 1.45[1.33, 1.59]), Spondin-1 (HR[95%CI] 1.13 [1.06, 1.20]), tartrate-resistant acid phosphatase type 5 (HR[95%CI] 0.65[0.53, 0.78]) and neurogenis locus notch homolog protein 1 (NOTCH1) (HR[95%CI] 0.67[0.55, 0.80]). These associations persisted at p<0.01 after adjustment for age, estimated glomerular filtration and history of HF. CKD was a significant interaction term in the associations of NOTCH1 and Spondin-1 with HF. Pathway analysis showed a trend for higher representation of the Cardiac Hypertrophy and Complement/Coagulation pathways among proteins prognostic of HF in the CKD sub-group. CONCLUSIONS:These results suggest that markers of heart failure differ between patients with and without CKD. Further research is needed to validate novel markers in cohorts of patients with CKD and adjudicated HF events

Urinary Tubular Injury Biomarkers Are Associated With ESRD and Death in the REGARDS Study.

IntroductionUrinary neutrophil gelatinase-associated lipocalin (uNGAL) and urinary kidney injury molecule-1 (uKIM-1) are established markers of subclinical acute kidney injury. In persons with reduced estimated glomerular filtration rate (eGFR) and albuminuria who are at high risk for end-stage renal disease (ESRD) and death, the associations of these urinary markers with incident ESRD or death is an area of active investigation.MethodsAmong 1472 black and white participants from the REasons for Geographic and Racial Differences in Stroke (REGARDS) study with eGFR ≤60 ml/min per 1.73 m2 (Chronic Kidney Disease Epidemiology Collaboration [CKD-EPI] cystatin, 2012) and albumin-to-creatinine ratio (ACR) ≥30 mg/g, we evaluated the associations of baseline uNGAL and uKIM-1 with progression to ESRD and all-cause death. Cox models were sequentially adjusted for urinary creatinine, traditional risk factors, C-reactive protein, ACR, and eGFR.ResultsThere were 257 ESRD events and 819 deaths over a median follow-up of 5.7 and 6.5 years, respectively. In demographic adjusted models, higher levels of uNGAL were associated with increased risk of ESRD and death, but these associations were attenuated in fully adjusted models including baseline eGFR for both ESRD (hazard ratio [HR] = 1.06 per doubling, 95% confidence interval [CI] 0.98-1.14) and death (HR = 1.04, 95% CI = 1.00-1.08). Higher levels of uKIM-1 were associated with increased risk of ESRD and death in demographic-adjusted models, and although attenuated in fully adjusted models, remained statistically significant for both ESRD (HR = 1.24 per doubling, 95% CI = 1.08-1.42) and death (HR = 1.10, 95% CI =1.03-1.19).ConclusionIn this cohort of high-risk patients with baseline eGFR ≤60 ml/min per 1.73 m2 and albuminuria, renal tubular injury is associated with higher mortality and progression to ESRD. Further studies are necessary to investigate the mechanism underlying this increased risk

161. The Potential Role of Extensor Muscle Fatigue in the Onset of Intervertebral Disc Degeneration: A Novel In Vivo Model

BACKGROUND CONTEXT: Occupation is strongly correlated to low back pain (LBP). Specific occupational activities associated with low back pain include poor posture, whole body vibration, and repetitive lifting. These activities have a common link: they result in fatigue of the primary spinal extensor musculature. This fatigue may lead to increased intervertebral loading - a stimulus for disc degeneration. If true, this association could provide a vital connection between detrimental physical activities and LBP. However, the link between muscle fatigue and increased load across the disc space has never been quantified in vivo. PURPOSE: The purpose of this study was to develop and test a wireless multi-axial force-sensing implant and large animal model of primary extensor muscle fatigue. Combined, these tools allow measurement of in vivo spinal forces during muscle fatigue to quantify changes in spine loading

Ethical Considerations for the Participation of Children of Minor Parents in Clinical Trials.

Children of minor parents are under-represented in clinical trials. This is largely because of the ethical, legal, and regulatory complexities in the enrolment, consent, and appropriate access of children of minor parents to clinical research. Using a case-based approach, we examine appropriate access of children of minor parents in an international vaccine trial. We first consider the scientific justification for inclusion of children of minor parents in a vaccine trial. Laws and regulations governing consent generally do not address the issue of minor parents. In their absence, local community and cultural contexts may influence consent processes. Rights of the minor parent include dignity in their role as a parent and respect for their decision-making capacity in that role. Rights of the child include the right to have decisions made in their best interest and the right to the highest attainable standard of health. Children of minor parents may have vulnerabilities related to the age of their parent, such as increased rates of poverty, that have implications for consent. Neuroscience research suggests that, by age 12-14 years, minors have adult-level capacity to make research decisions in situations with low emotion and low distraction. We conclude with a set of recommendations based on these findings to facilitate appropriate access and equity related to the participation of children of minor parents in clinical research

Generation tourism: towards a common identity

The purpose of this article is to highlight the implications of the indiscipline of tourism academia for a new generation of tourism academics. Generation Tourism is characterised by scholars with a multi-disciplinary education associated with a broad field of study and commonly considered to lack the advantages of a discipline-focused education with its strong theoretical and methodological foundations. The problem this article addresses relates to how new generations of scholars and their views on knowledge creation achieve ascendancy in ways that move on from existing paradigms and earlier cohorts of scholars. Our main argument is that Generation Tourism scholars would benefit from a more clearly developed and common academic identity. To begin the critical conversation around the identity of Generation Tourism we outline five possible points of departure. These points are: (1) learning from historical developments in parent disciplines; (2) spearheading inter-disciplinary scholarship; (3) working towards theoretical developments; (4) embracing mediating methodologies and (5) forming tourism nodes and networks. Recognising these as starting points rather than final statements, we hope that the conversation about Generation Tourism identity will continue in other forums

Diagnosis and management of Cornelia de Lange syndrome:first international consensus statement

Cornelia de Lange syndrome (CdLS) is an archetypical genetic syndrome that is characterized by intellectual disability, well-defined facial features, upper limb anomalies and atypical growth, among numerous other signs and symptoms. It is caused by variants in any one of seven genes, all of which have a structural or regulatory function in the cohesin complex. Although recent advances in next-generation sequencing have improved molecular diagnostics, marked heterogeneity exists in clinical and molecular diagnostic approaches and care practices worldwide. Here, we outline a series of recommendations that document the consensus of a group of international experts on clinical diagnostic criteria, both for classic CdLS and non-classic CdLS phenotypes, molecular investigations, long-term management and care planning

161. The Potential Role of Extensor Muscle Fatigue in the Onset of Intervertebral Disc Degeneration: A Novel In Vivo Model

BACKGROUND CONTEXT: Occupation is strongly correlated to low back pain (LBP). Specific occupational activities associated with low back pain include poor posture, whole body vibration, and repetitive lifting. These activities have a common link: they result in fatigue of the primary spinal extensor musculature. This fatigue may lead to increased intervertebral loading - a stimulus for disc degeneration. If true, this association could provide a vital connection between detrimental physical activities and LBP. However, the link between muscle fatigue and increased load across the disc space has never been quantified in vivo. PURPOSE: The purpose of this study was to develop and test a wireless multi-axial force-sensing implant and large animal model of primary extensor muscle fatigue. Combined, these tools allow measurement of in vivo spinal forces during muscle fatigue to quantify changes in spine loading

A Prospective, Longitudinal Outcome Study of Patients with Carpal Tunnel Surgery and the Relationship of Body Mass Index

This study investigated whether body mass index (BMI) was associated with effectiveness of carpal tunnel release as measured by physical and self-assessment tests. This prospective, longitudinal study was conducted from March 2001 to March 2003 using 598 cases (hands) diagnosed with carpal tunnel syndrome and scheduled for surgery at The Curtis National Hand Center, Baltimore, Maryland, and at the Pulvertaft Hand Centre, Derby, England. Body mass index was calculated, and demographic, clinical, and functional data were collected preoperatively and at 6-month follow-up. Grip, pinch, and Semmes–Weinstein scores were measured preoperatively and at 6-month follow-up. Levine–Katz self-assessment scores for symptom severity and functional status were measured preoperatively and at 6-month follow-up. Grip and pinch increased, whereas Semmes–Weinstein, symptom severity, and functional scores decreased by 6-month follow-up. Cases with BMI >35 had lower grip strength and higher symptom severity in males and higher functional status in both sexes pre- and postoperatively compared to normal-weight BMI cases. BMI had no relationship to patient satisfaction. Although morbidly obese cases did worse on some physical and self-assessment tests compared to normal BMI cases preoperatively, all improved to the same extent postoperatively regardless of BMI