The essentially constant glomerular cell density in nondiabetic and diabetic subjects under different circumstances possibly indicates an underlying propensity for the glomerulus to regulate its architecture to maintain a constant number of cells per volume, no matter the size of the glomerulus or the severity of diabetic nephropathy studied in this set of patients. The reductions in podocyte numbers in both younger and older diabetic patients indicate a significant risk for functional abnormalities as diabetic nephropathy progresses. Moreover, these observations do not support the suggestion of marked increases in glomerular cell number (and especially mesangial cells) with the development and progression of diabetic nephropathy.

The essentially constant glomerular cell density in nondiabetic and diabetic subjects under different circumstances possibly indicates an underlying propensity for the glomerulus to regulate its architecture to maintain a constant number of cells per volume, no matter the size of the glomerulus or the severity of diabetic nephropathy studied in this set of patients. The reductions in podocyte numbers in both younger and older diabetic patients indicate a significant risk for functional abnormalities as diabetic nephropathy progresses. Moreover, these observations do not support the suggestion of marked increases in glomerular cell number (and especially mesangial cells) with the development and progression of diabetic nephropathy.

No abstract

IMPORTANCE Soy isoflavone supplements are used to treat several chronic diseases, although the data supporting their use are limited. Some data suggest that supplementation with soy isoflavone may be an effective treatment for patients with poor asthma control.OBJECTIVE To determine whether a soy isoflavone supplement improves asthma control in adolescent and adult patients with poorly controlled disease. DESIGN, SETTING, AND PARTICIPANTS Multicenter, randomized, double-blind, placebo-controlled trial conducted between May 2010 and August 2012 at 19 adult and pediatric pulmonary and allergy centers in the American Lung Association Asthma Clinical Research Centers network. Three hundred eighty-six adults and children aged 12 years or older with symptomatic asthma while taking a controller medicine and low dietary soy intake were randomized, and 345 (89%) completed spirometry at week 24.INTERVENTIONS Participants were randomly assigned to receive soy isoflavone supplement containing 100 mg of total isoflavones (n=193) or matching placebo (n=193) in 2 divided doses administered daily for 24 weeks. MAIN OUTCOMES AND MEASURESThe primary outcome measure was change in forced expiratory volume in the first second (FEV 1 ) at 24 weeks. Secondary outcome measures were symptoms, episodes of poor asthma control, Asthma Control Test score (range, 5-25; higher scores indicate better control), and systemic and airway biomarkers of inflammation.RESULTS Mean changes in prebronchodilator FEV 1 over 24 weeks were 0.03 L (95% CI, −0.01 to 0.08 L) in the placebo group and 0.01 L (95% CI, −0.07 to 0.07 L) in the soy isoflavone group, which were not significantly different (P = .36). Mean changes in symptom scores on the Asthma Control Test (placebo, 1.98 [95% CI,] vs soy isoflavones, 2.20 [95% CI, 1.53-2.87]; positive values indicate a reduction in symptoms), number of episodes of poor asthma control (placebo, 3.3 [95% CI, 2.7-4.1] vs soy isoflavones, 3.0 [95% CI, 2.4-3.7]), and changes in exhaled nitric oxide (placebo, −3.48 ppb [95% CI, −5.99 to −0.97 ppb] vs soy isoflavones, 1.39 ppb [95% CI, −1.73 to 4.51 ppb]) did not significantly improve more with the soy isoflavone supplement than with placebo. Mean plasma genistein level increased from 4.87 ng/mL to 37.67 ng/mL (P < .001) in participants receiving the supplement.CONCLUSIONS AND RELEVANCE Among adults and children aged 12 years or older with poorly controlled asthma while taking a controller medication, use of a soy isoflavone supplement, compared with placebo, did not result in improved lung function or clinical outcomes. These findings suggest that this supplement should not be used for patients with poorly controlled asthma.

U rinary incontinence is a common problem, affecting up to two-thirds of all women. Its prevalence is easily underestimated in the clinical setting, since patients will often fail to bring the condition to the attention of their physician; it is estimated that only 1 in 4 symptomatic women seek help for this problem.1 By recent estimate, the total annual cost of urinary incontinence in the United States is about US$19.5 billion.2 In addition to affecting quality of life, complications of urinary incontinence include urinary retention, chronic lower urinary tract infection and vesicoureteral reflux, all of which affect health greatly. The aim of this review is to give primary care practitioners an overview of the current understanding of the taxonomy, pathophysiology, evaluation and treatment of female urinary incontinence. PathophysiologyPatients present with symptoms rather than diagnoses -an important distinction in the discussion of female urinary incontinence. Most patients with any degree of urinary incontinence will have symptoms that point to stress incontinence, urge incontinence or mixed incontinence. The symptom of stress urinary incontinence is the involuntary loss of urine accompanying sudden increases in intra-abdominal pressure (i.e., "stress"); this loss is sudden, coincident with the stressor and usually without warning. Urge incontinence occurs when an overwhelming urge to void results in leakage of urine; about half of all patients with overactive bladder syndrome experience urge incontinence.3 Mixed incontinence is the concurrence of stress and urge incontinence symptoms.As the bladder fills, sensory afferent signals are carried via the pelvic and hypogastric nerves to the spinal cord ( Fig. 1), where they are relayed to the pontine micturition centre via the lateral spinothalamic tracts and dorsal columns. Sympathetic tonus via the hypogastric nerve maintains smooth musclebased activity of the urethral sphincter and aids in detrusor relaxation, which thus promotes urine storage. Somatic efferent signals to the striated muscle of the pelvic floor via the pudendal nerve provide voluntary urethral sphincter activity, as well as momentary augmentation of urethral resistance in response to sudden increases in bladder pressure. As afferent signaling increases in intensity with bladder filling, a threshold of consciousness is reached, at which point a socially appropriate opportunity to void is sought. With permission to void, pontine signaling to the sacral cord via reticulospinal and corticospinal tracts results in parasympathetic cholinergic activation of the detrusor and reflex relaxation of the striated muscle of the pelvic floor, which allows pressurized urine flow. 4Neurologic insults commonly cause involuntary detrusor contractions and urinary incontinence by interrupting the pathways that control and coordinate the micturition reflex. Although lesions and conditions may vary in their effect on voiding dysfunction and incontinence, central nervous system lesions at or above the thoracic spin...