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To meet the diagnostic criteria for cEDS, a person must meet: Major criterion 1 AND major criterion 2 OR Major criterion 1 AND three or more minor criteria Major Criteria Skin hyperextensibility and atrophic scarring Generalized joint hypermobility Minor Criteria Easy bruising Soft, doughy skin Skin fragility (or traumatic splitting) Molluscoid pseudotumors Subcutaneous spheroids Hernia (or history thereof) Epicanthal folds Complications of joint hypermobility (e.g., sprains, dislocations/subluxations, pain, flexible flatfoot) Family history of a first-degree relative who meets clinical criteria Hypermobility Spectrum Disorders (HSD) HSD in Adults Adults are diagnosed with HSD if they have symptomatic joint hypermobility that cannot be explained by other conditions

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In humans, kidney removes 68 U of insulin per day by two major routes (Figure 2), that apparently have distinct preferential physiological goals: post-glomerular secretion (insulin signaling) and glomerular filtration (nutrient conservation and homeostasis) (Ritz et al., 2013)