Parental perceptions of second opinion consultations for recent onset schizophrenia.

AIM: Correct early diagnosis and intervention for schizophrenia is associated with improved outcomes. This study sought to determine the potential value of specialized consultations for individuals thought to have a recent-onset schizophrenia spectrum disorder who were not receiving specialized care. METHODS: 121 consecutive one-time consultations were performed in a clinic specializing in recent-onset schizophrenia. Parents of 79 patients were questioned about the process and the value of the consultation. RESULTS: Consultations were perceived by parents as both positive and helpful experiences. 85% of parents were somewhat or very happy with the consultation experience, and 86% found the consultation to be moderately or very helpful. A third of parents viewed the consultation as contributing to the long-term improvement of the patient's condition. CONCLUSIONS: The findings demonstrate the potential value of consultations for individuals with possible schizophrenia spectrum disorders not receiving specialized treatment, and provide rationale for comprehensive studies investigating the widespread implementation of such consultations.

Suicide and Maternal Mortality.

PURPOSE OF REVIEW: Suicide is a leading cause of death in the perinatal period (pregnancy and 1 year postpartum). We review recent findings on prevalence, risk factors, outcomes, and prevention and intervention for suicide during pregnancy and the first year postpartum. RECENT FINDINGS: Standardization of definitions and ascertainment of maternal deaths have improved identification of perinatal deaths by suicide and risk factors for perinatal suicide. Reports of a protective effect of pregnancy and postpartum on suicide risk may be inflated. Clinicians must be vigilant for risk of suicide among their perinatal patients, especially those with mental health diagnoses or prior suicide attempts. Pregnancy and the year postpartum are a time of increased access to healthcare for many, offering many opportunities to identify and intervene for suicide risk. Universal screening for suicide as part of assessment of depression and anxiety along with improved access to mental health treatments can reduce risk of perinatal suicide.

Effect of Protease Inhibitors in Healing of the Vaginal Wall.

Impaired elastogenesis and increased degradation of elastic fibers has been implicated in the pathogenesis of pelvic organ prolapse. Loss of the elastogenic organizer, fibulin-5 (FBLN5), leads to pelvic organ prolapse in mice. The objective of this study was to investigate the regulation of FBLN5 after surgical injury of the vaginal wall using the rat as a preclinical animal model. Both endogenous and recombinant FBLN5 were degraded after surgical injury. Estrogen did not alter the dramatic loss of vaginal FBLN5 in the acute phase after injury (12-48 h), but resulted in rescue of the poor recovery of FBLN5 levels in the late phase (7 d) of healing in ovariectomized animals. In contrast with estrogen, the general MMP inhibitor, actinonin, abrogated injury-induced degradation of FBLN5 significantly. Further, actinonin rescued the negative effects of injury on biomechanics, histomorphology, and elastic fibers. Control of excessive matrix degradation by local application of actinonin at the time of surgery may lead to improved elastic fiber regeneration and wound healing, thereby potentially enhancing pelvic floor recovery after reconstructive surgery for prolapse.

Onset and Remission of Psychosis in Parkinson's Disease: Pharmacologic and Motoric Markers.

BACKGROUND: Psychosis is among the most disabling complications of Parkinson's disease (PD). The chronicity of PD psychosis remains understudied and the relative importance of dopaminergic therapy versus the disease process itself in engendering psychosis remains unclear. OBJECTIVES: To examine pharmacologic and motoric correlates of PD psychosis onset and remission in a longitudinally monitored PD cohort. METHODS: We analyzed data from 165 participants enrolled in a longitudinal PD study through the Morris K. Udall Parkinson's Disease Research Center of Excellence at Johns Hopkins University. Evaluations included formal psychiatric assessment and were conducted at two-year intervals. Regression with generalized estimated equations (GEE) was used to produce unadjusted and adjusted estimates for time-varying longitudinal associations between psychosis and putative risk factors. RESULTS: Sixty-two participants (37.6%) were diagnosed with psychosis during at least one evaluation. Of forty-nine participants with psychosis followed over multiple evaluations, 13 (26.5%) demonstrated remission despite significant Hoehn & Yahr stage increase (p=0.009); two of these cases later relapsed. Multivariable regression with GEE identified dementia diagnosis, akinesia-rigidity, anticholinergic usage, and levodopa-carbidopa dose to be significantly associated with psychosis, while disease duration was not. A sub-analysis of 30 incident psychosis cases suggested that dopamine agonist dose was lowered after psychosis onset with a compensatory increase in levodopa-carbidopa dosage. CONCLUSIONS: Our findings suggest that in the context of standard therapy, PD-related psychotic disorder can remit at a frequency of approximately 27%. Additionally, akinetic-rigid motor impairment was more strongly associated with psychosis than disease duration, independent of cognitive impairment and medications.

Physical Activity, Vitamin D, and Incident Atherosclerotic Cardiovascular Disease in Whites and Blacks: The ARIC Study.

Context: Physical activity (PA) is associated with 25-hydroxyvitamin D [25(OH)D] levels. Both are associated with atherosclerotic cardiovascular disease (ASCVD), but their joint association with ASCVD risk is unknown. Objective: To examine the relationship between PA and 25(OH)D, and assess effect modification of 25(OH)D and PA with ASCVD. Design: Cross-sectional and prospective study. Setting: Community-dwelling cohort. Participants: A total of 10,342 participants free of ASCVD, with moderate- to vigorous-intensity PA assessed (1987 to 1989) and categorized per American Heart Association (AHA) guidelines (recommended, intermediate, or poor). Main Outcome Measures: Serum 25(OH)D levels (1990 to 1992) and ASCVD events (i.e., incident myocardial infarction, fatal coronary disease, or stroke) through 2013. Results: Participants had mean age of 54 years, and were 57% women, 21% black, 30% 25(OH)D deficient [<20 ng/mL (<50 nmol/L)], and <40% meeting AHA-recommended PA. PA was linearly associated with 25(OH)D levels in whites. Whites meeting recommended PA were 37% less likely to have 25(OH)D deficiency [relative risk, 0.63 (95% confidence interval [CI], 0.56, 0.71)]; there was no significant association in blacks. Over 19.3 years of follow-up, 1800 incident ASCVD events occurred. Recommended PA was associated with reduced ASCVD risk [hazard ratio [HR], 0.78 (95% CI, 0.65, 0.93) and 0.76 (95% CI, 0.62, 0.93)] among participants with intermediate [20 to <30 ng/mL (50 to <75 nmol/L)] and optimal [≥30 ng/mL (≥75 nmol/L)] 25(OH)D, respectively, but not among those with deficient 25(OH)D (P for interaction = 0.04). Conclusion: PA is linearly associated with higher 25(OH)D levels in whites. PA and 25(OH)D may have synergistic beneficial effects on ASCVD risk.

Vitamin D, Calcium, and Cardiovascular Disease: A"D"vantageous or "D"etrimental? An Era of Uncertainty.

While the function of vitamin D in regulating calcium homeostasis is well established, there has been growing interest in its role in the prevention of numerous chronic diseases, including cardiovascular disease (CVD). There is mounting epidemiological evidence suggesting that vitamin D deficiency is linked to increased CVD risk. However, the results of previous vitamin D supplementation trials have yielded mixed results in regards to cardiovascular health, and the results of ongoing large-scale randomized controlled trials are not yet available. Further complicating the issue, calcium supplementation, which is often prescribed concurrently with vitamin D, has been associated with increased CVD risk in some (but not all) studies. Thus, it is currently unclear whether vitamin D supplements, particularly for those that are deficient, can help prevent the development of CVD. In addition, there has not been uniform consensus regarding the threshold of 25-hydroxyvitamin D levels that constitutes "sufficiency" across organizational guidelines. This review will provide an update on the most recent evidence regarding the effects of vitamin D and calcium supplements on CVD clinical outcomes, summarize ongoing vitamin D trials, and discuss the current but remarkably disparate recommendations regarding vitamin D deficiency screening and supplementation.

Pelvic Organ Support in Animals with Partial Loss of Fibulin-5 in the Vaginal Wall.

Compromise of elastic fiber integrity in connective tissues of the pelvic floor is most likely acquired through aging, childbirth-associated injury, and genetic susceptibility. Mouse models of pelvic organ prolapse demonstrate systemic deficiencies in proteins that affect elastogenesis. Prolapse, however, does not occur until several months after birth and is thereby acquired with age or after parturition. To determine the impact of compromised levels of fibulin-5 (Fbln5) during adulthood on pelvic organ support after parturition and elastase-induced injury, tissue-specific conditional knockout (cKO) mice were generated in which doxycycline (dox) treatment results in deletion of Fbln5 in cells that utilize the smooth muscle α actin promoter-driven reverse tetracycline transactivator and tetracycline responsive element-Cre recombinase (i.e., Fbln5f/f/SMA++-rtTA/Cre+, cKO). Fbln5 was decreased significantly in the vagina of cKO mice compared with dox-treated wild type or controls (Fbln5f/f/SMA++-rtTA/Cre-/-). In controls, perineal body length (PBL) and bulge increased significantly after delivery but declined to baseline values within 6-8 weeks. Although overt prolapse did not occur in cKO animals, these transient increases in PBL postpartum were amplified and, unlike controls, parturition-induced increases in PBL (and bulge) did not recover to baseline but remained significantly increased for 12 wks. This lack of recovery from parturition was associated with increased MMP-9 and nondetectable levels of Fbln5 in the postpartum vagina. This predisposition to prolapse was accentuated by injection of elastase into the vaginal wall in which overt prolapse occurred in cKO animals, but rarely in controls. Taken together, our model system in which Fbln5 is conditionally knock-downed in stromal cells of the pelvic floor results in animals that undergo normal elastogenesis during development but lose Fbln5 as adults. The results indicate that vaginal fibulin-5 during development is crucial for baseline pelvic organ support and is also important for protection and recovery from parturition- and elastase-induced prolapse.

Safety of Manual Morcellation After Vaginal or Laparoscopic-assisted Vaginal Hysterectomy.

UNLABELLED: STUDY OBJECTIVE: To determine the safety of manual vaginal morcellation by evaluating the rates of incidental uterine malignancy and manual vaginal morcellation after vaginal or laparoscopic-assisted vaginal hysterectomy. DESIGN: Retrospective analysis (Canadian Task Force classification II-2). SETTING: University of Texas Southwestern Medical Center, Dallas, TX. PATIENTS: Women (n = 1,629) undergoing vaginal or laparoscopic-assisted vaginal hysterectomy. INTERVENTIONS: Vaginal hysterectomy (n = 1,091) or laparoscopic-assisted vaginal hysterectomy (n = 538) with and without scalpel morcellation. MEASUREMENTS AND MAIN RESULTS: The number of uterine malignancies, rate of vaginal morcellation, surgical indications, pathology diagnoses, and uterine weights were evaluated. Chi-square analysis was used to compare categoric data, and analysis of variance was used to compare uterine weights. There were no cases of leiomyosarcomas. There were 2 other sarcomas, 4 smooth muscle tumors of uncertain malignant potential, and 8 endometrial adenocarcinomas. The vaginal morcellation rate was 19.4%, but no malignancy was morcellated. Myomas were more common preoperatively and histologically in morcellated specimens. Mean (± standard deviation) uterine weights for morcellated versus nonmorcellated laparoscopic-assisted vaginal hysterectomy specimens were 285.5 ± 159.3 versus 140.1 ± 83.6 g (p < .001), respectively, and 199.9 ± 92.8 versus 111.9 ± 61.4 (p < .001), respectively, for vaginal hysterectomy. CONCLUSION: Vaginal manual morcellation is safe with a low risk of incidental malignancy. Variables that influence the decision for the vaginal approach may also affect malignancy risk and morcellation decisions. Thus, all patients undergoing vaginal or laparoscopic-assisted vaginal hysterectomy should be counseled regarding incidental malignancy, risk of morcellation, and alternatives for intact specimen removal.

Anatomic variations of pudendal nerve within pelvis and pudendal canal: clinical applications.

OBJECTIVE: The objective of the study was to examine the anatomic variation of the pudendal nerve in the pelvis, on the dorsal surface of the sacrospinous ligament, and in the pudendal canal. STUDY DESIGN: Detailed dissections of the pudendal nerve were performed in unembalmed female cadavers. Pelvic measurements included the distance from the origin of the pudendal nerve to the tip of ischial spine and the nerve width at its origin. The length of the pudendal canal was measured. The inferior rectal nerve was identified in the ischioanal fossa and its course documented. Lastly, the relationship of the pudendal nerve to the dorsal surface of the sacrospinous ligament was examined after transecting the lateral surface of the sacrospinous ligament. Descriptive statistics were used for data analyses and reporting. RESULTS: Thirteen female cadavers (26 hemipelvises) were examined. A single pudendal nerve trunk was identified in 61.5% of hemipelvises. The median distance from the point of the pudendal nerve formation to the ischial spine was 27.5 mm (range, 14.5-37 mm). The width of the pudendal nerve in the pelvis was 4.5 mm (range, 2.5-6.3 mm). The length of the pudendal canal was 40.5 mm (range, 20.5-54.5 mm). The inferior rectal nerve was noted to enter the pudendal canal in 42.3% of hemipelvises; in these cases, the nerve exited the canal at a distance of 32.5 mm (range, 16-45 mm) from the ischial spine. In the remaining specimens, the inferior rectal nerve passed behind the sacrospinous ligament and entered the ischioanal fossa without entering the pudendal canal. In all specimens, the pudendal nerve was fixed by connective tissue to the dorsal surface of the sacrospinous ligament. CONCLUSION: Great variability exists in pudendal nerve anatomy. Fixation of the pudendal nerve to the dorsal surface of the sacrospinous ligament is a consistent finding; thus, pudendal neuralgia attributed to nerve entrapment may be overestimated. The path of the inferior rectal nerve relative to the pudendal canal may have implications in the development of anorectal symptoms. Improved characterization of the pudendal nerve and its branches can help avoid intraoperative complications and enhance existing treatment modalities for pudendal neuropathy.

Deletion of macrophage Vitamin D receptor promotes insulin resistance and monocyte cholesterol transport to accelerate atherosclerosis in mice.

Intense effort has been devoted to understanding predisposition to chronic systemic inflammation because it contributes to cardiometabolic disease. We demonstrate that deletion of the macrophage vitamin D receptor (VDR) in mice (KODMAC) is sufficient to induce insulin resistance by promoting M2 macrophage accumulation in the liver as well as increasing cytokine secretion and hepatic glucose production. Moreover, VDR deletion increases atherosclerosis by enabling lipid-laden M2 monocytes to adhere, migrate, and carry cholesterol into the atherosclerotic plaque and by increasing macrophage cholesterol uptake and esterification. Increased foam cell formation results from lack of VDR-SERCA2b interaction, causing SERCA dysfunction, activation of ER stress-CaMKII-JNKp-PPARγ signaling, and induction of the scavenger receptors CD36 and SR-A1. Bone marrow transplant of VDR-expressing cells into KODMAC mice improved insulin sensitivity, suppressed atherosclerosis, and decreased foam cell formation. The immunomodulatory effects of vitamin D in macrophages are thus critical in diet-induced insulin resistance and atherosclerosis in mice.

Obstetrics and fecal incontinence.

Anal incontinence (AI) can be a debilitating condition for women following vaginal delivery. Operative vaginal delivery and anal sphincter laceration are important risk factors for the development of postpartum AI. Obtaining a comprehensive delivery history, along with a thorough physical examination of the perineum, vagina and rectum may aid the clinician in the diagnosis of an anal sphincter defect. Sonographic imaging can also assist in identifying sphincter defects. The treatment of AI may include a combination of dietary modification, medications that promote constipation, pelvic floor physical therapy, biofeedback, anal sphincteroplasty, and/or sacral neuromodulation.

Anatomic relationships of psoas muscle: clinical applications to psoas hitch ureteral reimplantation.

OBJECTIVE: The objective of the study was to examine the anatomic relationship of the genitofemoral and femoral nerves to the psoas major muscle. STUDY DESIGN: Dissections were performed in 17 unembalmed female cadavers. Point A was used as the approximate location for placement of psoas hitch sutures and as the reference point from which all measurements were taken. Measurements included the width of the psoas major muscle, psoas minor tendon, genitofemoral nerve branches, and femoral nerve. The relative location of the genitofemoral and femoral nerves to point A and the presence or absence of a psoas minor tendon were documented. RESULTS: The psoas minor tendon was absent on at least 1 side in 11 specimens (64.7%). The median width of the psoas minor tendon was 7 mm (range, 3-11.5 mm). The median width and depth of the psoas major muscle was 21.5 mm (range, 10-35 mm) and 20.0 mm (range, 11.5-32 mm), respectively. The median width of the genitofemoral nerve was 2 mm (range, 1-4.5 mm) and that of the femoral nerve was 6.3 mm (range, 5-10.5 mm). Overall, 54 genitofemoral nerve branches were identified in 17 cadavers, 30 medial (55.5%), 22 lateral (40.7%), and 2 directly overlying point A (3.7%). CONCLUSION: The exact location for the placement of the psoas hitch sutures will vary, depending on the location of the ureteral injury and the anatomy of the psoas muscle and surrounding structures. A thorough understanding of this regional anatomy should optimize the placement of psoas hitch sutures during ureteral reimplantation procedures and help avoid nerve and vessel injury.

Cystolith formation complicating single-incision sling.

Single-incision slings are the newest midurethral slings developed for the surgical treatment of stress urinary incontinence. We report the case of a patient who underwent single-incision sling placement who presented with recurrent stress incontinence 3 years after the procedure. She was found to have a 1.7-cm bladder stone that formed around the single-incision sling polypropylene barb.

Vitamin D deficiency induces high blood pressure and accelerates atherosclerosis in mice.

Multiple epidemiological studies link vitamin D deficiency to increased cardiovascular disease (CVD), but causality and possible mechanisms underlying these associations are not established. To clarify the role of vitamin D-deficiency in CVD in vivo, we generated mouse models of diet-induced vitamin D deficiency in two backgrounds (LDL receptor- and ApoE-null mice) that resemble humans with diet-induced hypertension and atherosclerosis. Mice were fed vitamin D-deficient or -sufficient chow for 6 weeks and then switched to high fat (HF) vitamin D-deficient or -sufficient diet for 8-10 weeks. Mice with diet-induced vitamin D deficiency showed increased systolic and diastolic blood pressure, high plasma renin, and decreased urinary sodium excretion. Hypertension was reversed and renin was suppressed by returning chow-fed vitamin D-deficient mice to vitamin D-sufficient chow diet for 6 weeks. On a HF diet, vitamin D-deficient mice had ~2-fold greater atherosclerosis in the aortic arch and ~2-8-fold greater atherosclerosis in the thoracic and abdominal aorta compared to vitamin D-sufficient mice. In the aortic root, HF-fed vitamin D-deficient mice had increased macrophage infiltration with increased fat accumulation and endoplasmic reticulum (ER) stress activation, but a lower prevalence of the M1 macrophage phenotype within atherosclerotic plaques. Similarly, peritoneal macrophages from vitamin D-deficient mice displayed an M2-predominant phenotype with increased foam cell formation and ER stress. Treatment of vitamin D-deficient mice with the ER stress reliever PBA during HF feeding suppressed atherosclerosis, decreased peritoneal macrophage foam cell formation, and downregulated ER stress proteins without changing blood pressure. Thus, we suggest that vitamin D deficiency activates both the renin angiotensin system and macrophage ER stress to contribute to the development of hypertension and accelerated atherosclerosis, highlighting vitamin D replacement as a potential therapy to reduce blood pressure and atherosclerosis.

Immunizations, immunology, and autism.

Public fears of rising rates of children being diagnosed with autistic spectrum disorders has led to a fear that immunizations, specifically the measles-mumps-varicella vaccine (MMR), may trigger autism. This article reviews theories of immunization as a risk factor for autism, including thimerosal exposure. We also review theories of autoimmunity as a predisposing genetic risk in autistic patients. We summarize from multiple population-based studies and extensive review committee reports that neither immunization nor thimerosal exposure has been conclusively linked to autism. Current treatments for autoimmunity in autism are reviewed and summarized as being only anecdotally effective, with no controlled studies to conclusively determine effectiveness. The goal of this article is to allow child neurologists to effectively counsel parents of autistic patients about vaccination risks and treatment options in presumed cases of autoimmune dysfunction.