Variation in tibial functionality and fracture susceptibility among healthy, young adults arises from the acquisition of biologically distinct sets of traits

Physiological systems like bone respond to many genetic and environmental factors by adjusting traits in a highly coordinated, compensatory manner to establish organ‐level function. To be mechanically functional, a bone should be sufficiently stiff and strong to support physiological loads. Factors impairing this process are expected to compromise strength and increase fracture risk. We tested the hypotheses that individuals with reduced stiffness relative to body size will show an increased risk of fracturing and that reduced strength arises from the acquisition of biologically distinct sets of traits (ie, different combinations of morphological and tissue‐level mechanical properties). We assessed tibial functionality retrospectively for 336 young adult women and men engaged in military training, and calculated robustness (total area/bone length), cortical area (Ct.Ar), and tissue‐mineral density (TMD). These three traits explained 69% to 72% of the variation in tibial stiffness ( p  < 0.0001). Having reduced stiffness relative to body size (body weight × bone length) was associated with odds ratios of 1.5 (95% confidence interval [CI], 0.5–4.3) and 7.0 (95% CI, 2.0–25.1) for women and men, respectively, for developing a stress fracture based on radiography and scintigraphy. K‐means cluster analysis was used to segregate men and women into subgroups based on robustness, Ct.Ar, and TMD adjusted for body size. Stiffness varied 37% to 42% among the clusters ( p  < 0.0001, ANOVA). For men, 78% of stress fracture cases segregated to three clusters ( p  < 0.03, chi‐square). Clusters showing reduced function exhibited either slender tibias with the expected Ct.Ar and TMD relative to body size and robustness (ie, well‐adapted bones) or robust tibias with reduced residuals for Ct.Ar or TMD relative to body size and robustness (ie, poorly adapted bones). Thus, we show there are multiple biomechanical and thus biological pathways leading to reduced function and increased fracture risk. Our results have important implications for developing personalized preventative diagnostics and treatments.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/98270/1/jbmr1879.pd

The Effect of Prolonged Physical Activity Performed during Extreme Caloric Deprivation on Cardiac Function

Background: Endurance exercise may induce transient cardiac dysfunction. Data regarding the effect of caloric restriction on cardiac function is limited. We studied the effect of physical activity performed during extreme caloric deprivation on cardiac function. Methods: Thirty-nine healthy male soldiers (mean age 2060.3 years) were studied during a field training exercise lasted 85– 103 hours, with negligible food intake and unlimited water supply. Anthropometric measurements, echocardiographic examinations and blood and urine tests were performed before and after the training exercise. Results: Baseline VO2 max was 5965.5 ml/kg/min. Participants ’ mean weight reduction was 5.760.9 kg. There was an increase in plasma urea (11.662.6 to 15.863.8 mmol/L, p,0.001) and urine osmolarity (6926212 to 10946140 mmol/kg, p,0.001) and a decrease in sodium levels (140.561.0 to 136.662.1 mmol/L, p,0.001) at the end of the study. Significant alterations in diastolic parameters included a decrease in mitral E wave (93.6 to 83.5 cm/s; p = 0.003), without change in E/A and E/E9 ratios, and an increase in iso-volumic relaxation time (73.9 to 82.9 ms, p = 0.006). There was no change in left or right ventricular systolic function, or pulmonary arterial pressure. Brain natriuretic peptide (BNP) levels were significantly reduced post-training (median 9 to 0 pg/ml, p,0.001). There was no elevation in Troponin T or CRP levels. On multivariate analysis, BNP reduction correlated with sodium levels and weight reduction (R = 0.8, p,0.001)

Comprehensive Genotyping in Two Homogeneous Graves' Disease Samples Reveals Major and Novel HLA Association Alleles

BACKGROUND: Graves' disease (GD) is the leading cause of hyperthyroidism and thyroid eye disease inherited as a complex trait. Although geoepidemiology studies showed relatively higher prevalence of GD in Asians than in Caucasians, previous genetic studies were contradictory concerning whether and/or which human leukocyte antigen (HLA) alleles are associated with GD in Asians. METHODOLOGY/PRINCIPAL FINDINGS: We conducted a case-control association study (499 unrelated GD cases and 504 controls) and a replication in an independent family sample (419 GD individuals and their 282 relatives in 165 families). To minimize genetic and phenotypic heterogeneity, we included only ethnic Chinese Han population in Taiwan and excluded subjects with hypothyroidism. We performed direct and comprehensive genotyping of six classical HLA loci (HLA-A, -B, -C, -DPB1, -DQB1 and -DRB1) to 4-digit resolution. Combining the data of two sample populations, we found that B*46:01 (odds ratio under dominant model [OR]  = 1.33, Bonferroni corrected combined P [P(Bc)]  = 1.17 x 10⁻²), DPB1*05:01 (OR  = 2.34, P(Bc) = 2.58 x 10⁻¹⁰), DQB1*03:02 (OR  = 0.62, P(Bc)  = 1.97 x 10⁻²), DRB1*15:01 (OR  = 1.68, P(Bc) = 1.22 x 10⁻²) and DRB1*16:02 (OR  = 2.63, P(Bc)  = 1.46 x 10⁻⁵) were associated with GD. HLA-DPB1*05:01 is the major gene of GD in our population and singly accounts for 48.4% of population-attributable risk. CONCLUSIONS/SIGNIFICANCE: These GD-associated alleles we identified in ethnic Chinese Hans, and those identified in other Asian studies, are totally distinct from the known associated alleles in Caucasians. Identification of population-specific association alleles is the critical first step for individualized medicine. Furthermore, comparison between different susceptibility/protective alleles across populations could facilitate generation of novel hypothesis about GD pathophysiology and indicate a new direction for future investigation

Renal trauma: the current best practice

The kidneys are the most vulnerable genitourinary organ in trauma, as they are involved in up to 3.25% of trauma patients. The most common mechanism for renal injury is blunt trauma (predominantly by motor vehicle accidents and falls), while penetrating trauma (mainly caused by firearms and stab wound) comprise the rest. High-velocity weapons impose specifically problematic damage because of the high energy and collateral effect. The mainstay of renal trauma diagnosis is based on contrast-enhanced computed tomography (CT), which is indicated in all stable patients with gross hematuria and in patients presenting with microscopic hematuria and hypotension. Additionally, CT should be performed when the mechanism of injury or physical examination findings are suggestive of renal injury (e.g. rapid deceleration, rib fractures, flank ecchymosis, and every penetrating injury of the abdomen, flank or lower chest). Renal trauma management has evolved during the last decades, with a distinct evolution toward a nonoperative approach. The lion’s share of renal trauma patients are managed nonoperatively with careful monitoring, reimaging when there is any deterioration, and the use of minimally invasive procedures. These procedures include angioembolization in cases of active bleeding and endourological stenting in cases of urine extravasation

Changing Trends in Surgical Management of Nephrolithiasis among Young Adults: A 15-Year Population-Based Study

Background: Increases in obesity and diabetes rates among all ages have led to a greater prevalence of nephrolithiasis worldwide. We aimed to explore the changing trends in surgical management of nephrolithiasis in young adults over a 15 year period. Methods: We reviewed medical records of military personnel for information on the diagnosis and care of nephrolithiasis before and during active service between 2007&ndash;2021, divided into three 5 year periods: 2007&ndash;2011, 2012&ndash;2016, and 2017&ndash;2021. Demographic, clinical, radiological, and surgical data were retrieved for the analysis of changing trends. Results: The records of 1,117,692 recruits yielded 7383 (0.66%) with stone-related surgeries, of whom 1885 were operated during military service. Their median age was 19.6 years (interquartile range [IQR] 16.8&ndash;21.2), 829 (70%) were males, and the cohort&rsquo;s median body mass index was 23.6 (IQR 17.3&ndash;26.1). There was a dramatic decline in shock wave lithotripsy (SWL) prevalence (35.1%, 10.4%, and 4.4%, respectively) with a continually increasing prevalence of ureteroscopy (URS)/retrograde intrarenal surgery (RIRS) (62.7%, 88.5%, and 94.6%, p = 0.01). Percutaneous nephrolithotomy (PCNL) procedures have become nearly extinct over time (0.8% in 2017&ndash;2021). The number of median-sized stones treated by URS/RIRS increased (7.5 mm, 8.2 mm, and 9.7 mm, p = 0.044), but not those treated by SWL/PCNL. The median length of medical leave for URS/RIRS and PCNL decreased significantly (7 vs. 4 days, p = 0.05 and 10 vs. 6 days, p = 0.036, respectively), with no comparable change for SWL. There was a substantial decline in ancillary procedures in the URS/RIRS groups (9%, 6.8%, and 3.1%, p &lt; 0.01), but not in the SWL/PCNL groups. Conclusions: Advancements in technology and surgical training are leading to the extinction of SWL and the adoption of URS/RIRS as the new standard of care for nephrolithiasis among young adults

Pre- and post-training plasma levels of cardiac biomarkers.

<p>Results are presented as median (inter-quartile range).</p><p>BNP  =  brain natriuretic peptide; CRP = C reactive protein.</p

Echocardiographic parameters.

<p>LA = left atrium; LV = left ventricle; IVRT = iso-volumic relaxation time; RVFAC = right ventricular fractional area change; RA = right atrium.</p