Influences of obese (ob/ob) and diabetes (db/db) genotype mutations on lumber vertebral radiological and morphometric indices: Skeletal deformation associated with dysregulated systemic glucometabolism

BACKGROUND: Both diabetes and obesity syndromes are recognized to promote lumbar vertebral instability, premature osteodegeneration, exacerbate progressive osteoporosis and increase the propensity towards vertebral degeneration, instability and deformation in humans. METHODS: The influences of single-gene missense mutations, expressing either diabetes (db/db) or obese (ob/ob) metabolic syndromes on vertebral maturation and development in C57BL/KsJ mice were evaluated by radiological and macro-morphometric analysis of the resulting variances in osteodevelopment indices relative to control parameters between 8 and 16 weeks of age (syndrome onset @ 4 weeks), and the influences of low-dose 17-B-estradiol therapy on vertebral growth expression evaluated. RESULTS: Associated with the indicative genotypic obesity and hyper-glycemic/-insulinemic states, both db/db and ob/ob mutants demonstrated a significant (P ≤ 0.05) elongation of total lumbar vertebrae column (VC) regional length, and individual lumbar vertebrae (LV1-5) lengths, relative to control VC and LV parameters. In contrast, LV1-5 width indices were suppressed in db/db and ob/ob mutants relative to control LV growth rates. Between 8 and 16 weeks of age, the suppressed LV1-5 width indices were sustained in both genotype mutant groups relative to control osteomaturation rates. The severity of LV1-5 width osteosuppression correlated with the severe systemic hyperglycemic and hypertriglyceridemic conditions sustained in ob/ob and db/db mutants. Low-dose 17-B-estradiol therapy (E2-HRx: 1.0 ug/ 0.1 ml oil s.c/3.5 days), initiated at 4 weeks of age (i.e., initial onset phase of db/db and ob/ob expressions) re-established control LV 1–5 width indices without influencing VC or LV lengths in db/db groups. CONCLUSION: These data demonstrate that the abnormal systemic endometabolic states associated with the expression of db/db and ob/ob genomutation syndromes suppress LV 1–5 width osteomaturation rates, but enhanced development related VC and LV length expression, relative to control indices in a progressive manner similar to recognized human metabolic syndrome conditions. Therapeutic E2 modulation of the hyperglycemic component of diabetes-obesity syndrome protected the regional LV from the mutation-induced osteopenic width-growth suppression. These data suggest that these genotype mutation models may prove valuable for the evaluation of therapeutic methodologies suitable for the treatment of human diabetes- or obesity-influenced, LV degeneration-linked human conditions, which demonstrate amelioration from conventional replacement therapies following diagnosis of systemic syndrome-induced LV osteomaturation-associated deformations

What Does the Gig Economy Mean for Workers?

This report provides an overview of the gig economy -- i.e., the collection of markets that match providers to consumers on a gig (or job) basis in support of on-demand commerce (e.g., Uber, TaskRabbit) -- and identifies legal and policy questions relevant to its workforce

Expansion breccias in Lower Cretaceous Apennine pelagic limestones: I. Geological observations

Breccias affecting the pelagic Lower Cretaceous Maiolica limestone of the Umbria-Marche Apennines of central Italy contain 10-cm-diameter to submillimeter angular clasts of white pelagic limestone and black chert, separated by a filling of sparry calcite. The clasts can often be seen to have originally fitted together, indicat- ing extension without shear, and this is the case in all three dimensions, arguing for roughly isotropic volumetric expansion. Breccia fragments are separated by sparry calcite bodies comparable in width to the fragments; this shows that the breccias were not formed by collapse, or by a single large explosion, after either of which the frag- ments would surely have fallen to the bottom of the cavity, but probably by multiple small expansion events, each followed by calcite deposition in the small voids that opened up. The breccia sometimes occurs in dramatic topographic walls, a few tens of meters in both width and height, although there is not a one-to-one correspondence between breccia and walls. The sparry-calcite fill indicates that water with dissolved CO2 was involved in formation of the breccias, presumably providing the high fluid pressure that forced the fragments apart. The breccia is bounded stratigraphically above by the middle Cretaceous Marne a Fucoidi (Fucoid marls), which appears to represent an aquiclude that limited the volume of high fluid pressure (PF). Although the mechanism of formation of the expansion breccias is not yet clear, we list obser- vations that need to be accounted for by such a mechanism and discuss how these observations might be explained