Does Footfall Pattern in Forefoot Runners Change Over a Prolonged Run?

There has been much debate on the benefits of a forefoot versus rearfoot strike pattern in distance running in terms of performance and injury prevalence. Shock attenuation occurs more prominently in soft tissues at impact in forefoot runners compared to the passive skeletal loading in rearfoot runners. Recent studies indicate that a forefoot strike pattern may not be maintainable over long distance efforts. Therefore, this study tested the hypothesis that habitual forefoot runners could not maintain their strike pattern throughout a prolonged, intensive run. Fourteen forefoot runners ran to voluntary exhaustion on an instrumented force treadmill (average run duration: 15.4±2.2 minutes). Kinematic and kinetic data were sampled each minute at 200Hz and 1000Hz, respectively. Ankle plantar-flexor torque was measured during pre- and post-run isometric contractions, during which electromyographic activity was measured in the soleus, lateral, and medial gastrocnemius. Loading rate (49.95±14.83 to 57.40±22.53 BW*s-1, p=0.0311) and impact peak (1.35±0.43 to 1.50±0.51, p=0.0207) increased significantly throughout the run. Both peak knee flexion (-33.93±3.67º to -36.21±3.48º, p=\u3c0.0000) and sagittal ankle angle at touchdown (-11.83±5.33º to -9.33±6.29º, p =0.0202) increased significantly. Ankle torque decreased significantly from pre- to post-run (120.57±33.57 to 110.76±32.91 Nm, p = 0.0154). This was accompanied by a decrease in medial and lateral gastrocnemius integrated electromyographic activity (iEMG) (p=0.0387 and 0.0186, respectively). The results indicated that there were significant changes in landing mechanics in the habitual forefoot runners with increased levels of exertion, as they shifted towards strike patterns more similar to rearfoot runners throughout the run. These changes are in line with metabolic findings of other studies. There is increased eccentric loading of the ankle plantar-flexor muscles at touchdown in forefoot runners that may contribute to a decreased torque output by the end of the run. The decline in iEMG may indicate altered central drive of the system and a decline in the impact attenuation ability of the triceps surae, leading to the changes exhibited up the kinematic chain. These findings suggest that while forefoot strike patterns are good for speed, the onset of fatigue may affect the ability to maintain this pattern during a prolonged, intensive effort

Florbetapir F 18 amyloid PET and 36-month cognitive decline:a prospective multicenter study

This study was designed to evaluate whether subjects with amyloid beta (Aβ) pathology, detected using florbetapir positron emission tomorgraphy (PET), demonstrated greater cognitive decline than subjects without Aβ pathology. Sixty-nine cognitively normal (CN) controls, 52 with recently diagnosed mild cognitive impairment (MCI) and 31 with probable Alzheimer's disease (AD) dementia were included in the study. PET images obtained in these subjects were visually rated as positive (Aβ+) or negative (Aβ−), blind to diagnosis. Fourteen percent (10/69) of CN, 37% (19/52) of MCI and 68% (21/31) of AD were Aβ+. The primary outcome was change in ADAS-Cog score in MCI subjects after 36 months; however, additional outcomes included change on measures of cognition, function and diagnostic status. Aβ+ MCI subjects demonstrated greater worsening compared with Aβ− subjects on the ADAS-Cog over 36 months (5.66±1.47 vs −0.71±1.09, P=0.0014) as well as on the mini-mental state exam (MMSE), digit symbol substitution (DSS) test, and a verbal fluency test (P<0.05). Similar to MCI subjects, Aβ+ CN subjects showed greater decline on the ADAS-Cog, digit-symbol-substitution test and verbal fluency (P<0.05), whereas Aβ+ AD patients showed greater declines in verbal fluency and the MMSE (P<0.05). Aβ+ subjects in all diagnostic groups also showed greater decline on the CDR-SB (P<0.04), a global clinical assessment. Aβ+ subjects did not show significantly greater declines on the ADCS-ADL or Wechsler Memory Scale. Overall, these findings suggest that in CN, MCI and AD subjects, florbetapir PET Aβ+ subjects show greater cognitive and global deterioration over a 3-year follow-up than Aβ− subjects do

Genome-wide association identifies nine common variants associated with fasting proinsulin levels and provides new insights into the pathophysiology of type 2 diabetes.

OBJECTIVE: Proinsulin is a precursor of mature insulin and C-peptide. Higher circulating proinsulin levels are associated with impaired β-cell function, raised glucose levels, insulin resistance, and type 2 diabetes (T2D). Studies of the insulin processing pathway could provide new insights about T2D pathophysiology. RESEARCH DESIGN AND METHODS: We have conducted a meta-analysis of genome-wide association tests of ∼2.5 million genotyped or imputed single nucleotide polymorphisms (SNPs) and fasting proinsulin levels in 10,701 nondiabetic adults of European ancestry, with follow-up of 23 loci in up to 16,378 individuals, using additive genetic models adjusted for age, sex, fasting insulin, and study-specific covariates. RESULTS: Nine SNPs at eight loci were associated with proinsulin levels (P < 5 × 10(-8)). Two loci (LARP6 and SGSM2) have not been previously related to metabolic traits, one (MADD) has been associated with fasting glucose, one (PCSK1) has been implicated in obesity, and four (TCF7L2, SLC30A8, VPS13C/C2CD4A/B, and ARAP1, formerly CENTD2) increase T2D risk. The proinsulin-raising allele of ARAP1 was associated with a lower fasting glucose (P = 1.7 × 10(-4)), improved β-cell function (P = 1.1 × 10(-5)), and lower risk of T2D (odds ratio 0.88; P = 7.8 × 10(-6)). Notably, PCSK1 encodes the protein prohormone convertase 1/3, the first enzyme in the insulin processing pathway. A genotype score composed of the nine proinsulin-raising alleles was not associated with coronary disease in two large case-control datasets. CONCLUSIONS: We have identified nine genetic variants associated with fasting proinsulin. Our findings illuminate the biology underlying glucose homeostasis and T2D development in humans and argue against a direct role of proinsulin in coronary artery disease pathogenesis

Genetic determinants of ulcerative colitis include the ECM1 locus and five loci implicated in Crohn's disease.

We report results of a nonsynonymous SNP scan for ulcerative colitis and identify a previously unknown susceptibility locus at ECM1. We also show that several risk loci are common to ulcerative colitis and Crohn's disease (IL23R, IL12B, HLA, NKX2-3 and MST1), whereas autophagy genes ATG16L1 and IRGM, along with NOD2 (also known as CARD15), are specific for Crohn's disease. These data provide the first detailed illustration of the genetic relationship between these common inflammatory bowel diseases

Amyloid-&amp;bgr; assessed by florbetapir F 18 PET and 18-month cognitive decline

ObjectivesFlorbetapir F 18 PET can image amyloid-β (Aβ) aggregates in the brains of living subjects. We prospectively evaluated the prognostic utility of detecting Aβ pathology using florbetapir PET in subjects at risk for progressive cognitive decline.MethodsA total of 151 subjects who previously participated in a multicenter florbetapir PET imaging study were recruited for longitudinal assessment. Subjects included 51 with recently diagnosed mild cognitive impairment (MCI), 69 cognitively normal controls (CN), and 31 with clinically diagnosed Alzheimer disease dementia (AD). PET images were visually scored as positive (Aβ+) or negative (Aβ-) for pathologic levels of β-amyloid aggregation, blind to diagnostic classification. Cerebral to cerebellar standardized uptake value ratios (SUVr) were determined from the baseline PET images. Subjects were followed for 18 months to evaluate changes in cognition and diagnostic status. Analysis of covariance and correlation analyses were conducted to evaluate the association between baseline PET amyloid status and subsequent cognitive decline.ResultsIn both MCI and CN, baseline Aβ+ scans were associated with greater clinical worsening on the Alzheimer's Disease Assessment Scale-Cognitive subscale (ADAS-Cog (p &lt; 0.01) and Clinical Dementia Rating-sum of boxes (CDR-SB) (p &lt; 0.02). In MCI Aβ+ scans were also associated with greater decline in memory, Digit Symbol Substitution (DSS), and Mini-Mental State Examination (MMSE) (p &lt; 0.05). In MCI, higher baseline SUVr similarly correlated with greater subsequent decline on the ADAS-Cog (p &lt; 0.01), CDR-SB (p &lt; 0.03), a memory measure, DSS, and MMSE (p &lt; 0.05). Aβ+ MCI tended to convert to AD dementia at a higher rate than Aβ- subjects (p &lt; 0.10).ConclusionsFlorbetapir PET may help identify individuals at increased risk for progressive cognitive decline

Investigation of Crohn's Disease Risk Loci in Ulcerative Colitis Further Defines Their Molecular Relationship

BACKGROUND & AIMS: Identifying shared and disease-specific susceptibility loci for Crohn's disease (CD) and ulcerative colitis (UC) would help define the biologic relationship between the inflammatory bowel diseases. More than 30 CD susceptibility loci have been identified. These represent important candidate susceptibility loci for UC. Loci discovered by the index genome scans in CD have previously been tested for association with UC, but those identified in the recent meta-analysis await such investigation. Furthermore, the recently identified UC locus at ECM1 requires formal testing for association with CD. METHODS: We analyzed 45 single nucleotide polymorphisms, tagging 29 of the loci recently associated with CD in 2527 UC cases and 4070 population controls. We also genotyped the UC-associated ECM1 variant rs11205387 in 1560 CD patients and 3028 controls. RESULTS: Nine regions showed association with UC at a threshold corrected for the 29 loci tested (P < .0017). The strongest association (P = 4.13 x 10(-8); odds ratio = 1.27) was identified with a 170-kilobase region on chromosome 1q32 that contains 3 genes. We also found association with JAK2 and replicated a recently reported association with STAT3, further implicating the role of this signaling pathway in inflammatory bowel disease. Additional novel UC susceptibility genes were LYRM4 and CDKAL1. Twenty of the loci were not associated with UC, and several appear to be specific to CD. ECM1 variation was not associated with CD. CONCLUSIONS: Collectively, these data help define the genetic relationship between CD and UC and characterize common, as well as disease-specific mechanisms of pathogenesis