Antipsychotics increase vesicular glutamate transporter 2 (VGLUT2) expression in thalamolimbic pathways

Recently the two vesicular-glutamate-transporters VGLUT1 and VGLUT2 have been cloned and characterized. VGLUT1 and VGLUT2 together label all glutamatergic neurons, but because of their distinct expression patterns in the brain they facilitate our ability to define between a VGLUT1-positive cortical and a VGLUT2-positive subcortical glutamatergic systems. We have previously demonstrated an increased cortical VGLUT1 expression as marker of antidepressant activity. Here, we assessed the effects of different psychotropic drugs on brain VGLUT2 mRNA and protein expression. The typical antipsychotic haloperidol, and the atypicals clozapine and risperidone increased VGLUT2 mRNA selectively in the central medial/medial parafascicular, paraventricular and intermediodorsal thalamic nuclei; VGLUT2 protein was accordingly amplified in paraventricular and ventral striatum and in prefrontal cortex. The antidepressants fluoxetine and desipramine and the sedative anxiolytic diazepam had no effect. These results highlight the implication of thalamo-limbic glutamatergic pathways in the action of antipsychotics. Increased VGLUT2 expression in these neurons might constitute a marker for antipsychotic activity and subcortical glutamate neurotransmission might be a possible novel target for future generation antipsychotics.     

What women with ovarian cancer think and know about genetic testing

ObjectivesFew women with ovarian cancer undergo genetic testing for the Breast and Ovarian Cancer susceptibility genes, BRCA1 and BRCA2. With the prospect of BRCA-directed therapeutics, we investigated ovarian cancer patients' knowledge and willingness to undergo genetic testing.MethodsAll ovarian cancer patients seen in the Gynecology Center of a cancer center and a private clinic were asked to complete an anonymous questionnaire regarding knowledge and willingness to undergo BRCA testing. Women who had prior genetic testing were asked not to participate. Data was analyzed using Fisher's exact test.ResultsTwo-hundred and thirty seven ovarian cancer patients voluntarily completed the questionnaire. Fifty-five percent (131/237) of participants had not heard of BRCA testing. Of Caucasian respondents, 51% were unaware of BRCA testing, compared to 70% of Hispanic and 88% of African American respondents (p = 0.008). Awareness was correlated with education (p < 0.001). Eighty-nine percent of participants were willing to be tested if it would directly affect their therapy and 86.9% would be tested to benefit their family. Seventy-four percent of patients would pay 20% of the cost of testing, only 25.1% would pay in full.ConclusionsA majority of women with ovarian cancer are not aware of the availability of BRCA testing. This lack of awareness is more profound in minorities. Despite lack of knowledge, most patients would undergo testing if it would impact their care. However, cost may be a barrier. Given the willingness of patients to undergo testing and the possibility of targeted therapy, clinicians who care for these patients should work to make appropriate genetic counseling referrals.     

Complications of sling surgery among female Medicare beneficiaries

OBJECTIVE: To analyze Medicare claims data to determine short-term complications after sling surgery among female beneficiaries aged 65 years and over. METHODS: We analyzed the 1999-2001 Medicare Public Use Files provided by the Centers for Medicare and Medicaid Services on a 5% national random sample of beneficiaries. Women undergoing sling procedures between January 1, 1999, and July 31, 2000, (the index period) were identified by Physicians Current Procedural Terminology Coding System (4th edition) and tracked for 12 months. Main outcome measures were complications as identified by International Classification of Diseases (9th revision) (ICD-9) diagnosis codes and Current Procedural Terminology procedure codes in the first postoperative year. RESULTS: A total of 1,356 sling procedures were performed during the index period. In the 3 months after the procedure, 12.5% of women developed surgical or urologic complications, and 33.6% were diagnosed with urinary tract infections. Within 1 year of the procedure, 6.9% of subjects had a new diagnosis of outlet obstruction, and 8.0% underwent treatments to manage outlet obstruction. There was a high incidence of new diagnoses of urge incontinence (15.2%) and treatment of pelvic prolapse (23.2%). Both cystoscopy and urodynamic testing, which may serve as indicators of possible complications, were performed frequently during the first year after surgery (32.4% and 30.5%, respectively). Patient race, age, and comorbidity each had a significant influence on outcomes. CONCLUSION: Complication rates within 1 year after sling surgery among Medicare beneficiaries were found to be higher than those reported in the clinical literature. The high rates of postoperative urinary tract infections, prolapse, and outlet obstruction suggest the need for quality improvement measures in the management of women with incontinence and pelvic prolapse. LEVEL OF EVIDENCE: III.     

Predictors and Outcomes of Completion Axillary Node Dissection Among Older Breast Cancer Patients

Background

The role of completion axillary lymph node dissection (ALND) for older women who had sentinel lymph node-positive (SLN+) invasive breast cancer is unclear. We examined factors predictive of ALND and the association between ALND, adjuvant chemotherapy administration, and survival.

Methods

Using the Surveillance, Epidemiology, and End Results (SEER)-Medicare database, we reviewed records of women age >65 diagnosed with stage I/II breast cancer from 1998–2005. Adjusted Cox proportional hazards and multivariate logistic regression were used to identify patient and disease variables associated with ALND, and assess association between ALND and all-cause and breast cancer-specific survival.

Results

Among SLN+ patients, 88 % underwent ALND. Earlier diagnosis year, greater nodal involvement, younger age, registry location, and larger tumor size were all associated with a significantly higher likelihood of ALND. The ALND in SLN+ patients was not significantly associated with 5-year breast cancer-specific survival (hazard ratio [HR] 1.22, 95 % confidence interval [CI] 0.76–1.96). The SLN+ patients who underwent ALND were more likely to receive adjuvant chemotherapy (odds ratio [OR] 1.8, 95 % CI 1.45–2.24). However, younger age (OR 18.0, 95 % CI 14.4–23.9), estrogen receptor-negative (ER-) status (OR 4.2, 95 % CI 3.4–5.3), and fewer comorbidities (OR 2.6, 95 % CI 1.7–4.0) were all more strongly linked to receipt of chemotherapy.

Conclusions

ALND for older patients with SLN+ breast cancer is not associated with improved 5-year all-cause or breast cancer-specific survival. Younger age, fewer comorbidities, and estrogen receptor-negative (ER-) status were more strongly associated with receipt of chemotherapy than ALND. Consideration should be given to omitting ALND in older patients, particularly if findings of ALND will not influence adjuvant therapy decisions.     

Are Better Sleepers More Engaged Workers? A Self‐regulatory Approach to Sleep Hygiene and Work Engagement

Previous research has emphasized facets of both the organizational environment and individual differences as predictors of work engagement. This study explored sleep hygiene as another important behavioural factor that may be related to work engagement. With a sample of 328 adult workers, we tested a multiple mediator model in which sleep hygiene predicts work engagement through one's appraisals of resource depletion stemming from demands (psychological strain) and general self‐regulatory capacity (self‐control). Results indicated that individuals who frequently engaged in poor sleep hygiene behaviours had lower self‐regulatory capacity, experienced higher subjective depletion and were less engaged at work. Additionally, the path from poor sleep hygiene to decreased work engagement was attributed to perceptions of personal resources that are needed to exert self‐regulatory energy at work. This is consistent with current self‐regulatory theories suggesting that individuals have a limited amount of resources to allocate to demands and that the depletion of these resources can lead to stress and lower self‐regulatory functioning in response to other demands. Specifically, poor sleep hygiene results in the loss of self‐regulatory resources needed to be engaged in work tasks by impairing the after‐work recovery process. Practical and research implications regarding sleep hygiene interventions for well‐being and productivity improvement are discussed. Copyright © 2012 John Wiley & Sons, Ltd.     

Development and validation of the Workplace Interruptions Measure

In 3 studies, we developed and tested the first comprehensive, self‐report measure of workplace interruptions. The Workplace Interruptions Measure (WIM) is based on a typology of interruptions that included intrusions, distractions, discrepancy detections, and breaks. The four‐factor structure was reduced to a 12‐item measure in Study 1 (N = 317) and confirmed in a diverse sample of employees in Study 2 (N = 160). Study 3 (N = 323) further examined the psychometric properties of the WIM in a sample of university faculty and staff. Studies 2 and 3 demonstrated that both effort‐enhancing interruptions (intrusions, distractions, and discrepancy detections) and recovery‐enhancing interruptions (breaks) were associated with stressors and strains. Distractions, discrepancy detections, and breaks uniquely predicted strain outcomes beyond other workplace stressors (i.e., quantitative workload, interpersonal conflict, and role conflict). We discuss implications of the WIM for the theory and practice of interruptions research.     

HIV-Induced Cystopathy

The prevalence of voiding dysfunction in patients with HIV has decreased dramatically since the inception of highly active antiretroviral therapy (HAART) and therefore has not been an area that has been widely published. Prior research into this area was at the epidemic’s onset, when there was a large population of patients with opportunistic infections and associated voiding dysfunction. As the HAART patients are living longer and symptom-free lives, there is no current large population from which to draw in order to conduct sound studies. Through a comprehensive review of the literature, we discuss the most common causes of HIV-induced cystopathy to educate the practicing urologist about disease-related causes and to serve as a guide for the diagnosis and management of HIV-associated voiding dysfunction.