Identification of psychopathological course trajectories in schizophrenia

Course trajectory analyses have been performed primarily for treatment response in acute episodes of schizophrenic disorders. As yet, corresponding data for the long-term course are lacking. Within a multicenter prospective observational study, 268 patients with schizophrenia were assessed at discharge from hospital and followed up after 6, 12, 18, and 24 months. A latent class growth analysis was performed on the scores from the Positive and Negative Syndrome Scale (PANSS). A two-class conditional latent class model showed the best data fit (Entropy: 0.924). The model divided the sample into a group with amelioration in all PANSS subscales (60%) and a group with stable positive/negative and deteriorating general psychopathology symptoms (40%). Global functioning (GAF score), gender, age, living situation and involuntary admission predicted course trajectory class membership. The model was predictive of significant differences between the two groups in health care service costs and quality of life. The results underline the heterogeneous course of the illness, which ranged from amelioration to deterioration over a 2-year period. Statistical models such as trajectory analysis could help to identify more homogenous subtypes in schizophrenia.     

Survey of physician practices for community-dwelling agitated dementia patients

In order to gain a better understanding of physician clinical reasoning and clinical practices for community-dwelling agitated dementia patients, we conducted a small survey of geriatric psychiatrists, primary care physicians and neurologists. The survey asked physician respondents to give a likelihood estimate of how often they would carry out one of 13 different pharmacologic and psychosocial interventions. Intervention by specialty group analyses found that geriatric psychiatrists were more likely to recommend neuroleptic medications and dementia support group activities, but less likely to recommend referral to behavioral specialists than the other physician groups. Neurologists were more likely to recommend dementia support groups than primary care physicians, but they were also more likely to recommend institutional placement than the other physician groups. Primary care physicians were more likely to recommend hydroxyzine than either neurologists or geriatric psychiatrists. Multivariate ordinal logistic regression analysis found that older physicians and primary care physicians expressed a lower likelihood of recommending dementia day care programs and a higher likelihood of recommending hydroxyzine. Women physicians, however, expressed a high likelihood of recommending dementia day care programs. The results of the survey suggest that personal and specialty characteristics of physicians influence the types of treatment recommendations made for agitated dementia patients. The results may help community-based dementia care programs to develop strategies that broaden physician involvement in multidisciplinary team management for these patients.     

From the Cover: Association of improved air quality with lower dementia risk in older women

Late-life ambient air pollution is a risk factor for brain aging, but it remains unknown if improved air quality (AQ) lowers dementia risk. We studied a geographically diverse cohort of older women dementia free at baseline in 2008 to 2012 (n = 2,239, aged 74 to 92). Incident dementia was centrally adjudicated annually. Yearly mean concentrations of fine particulate matter (PM_2.5) and nitrogen dioxide (NO₂) were estimated using regionalized national universal kriging models and averaged over the 3-y period before baseline (recent exposure) and 10 y earlier (remote exposure). Reduction from remote to recent exposures was used as the indicator of improved AQ. Cox proportional hazard ratios (HRs) for dementia risk associated with AQ measures were estimated, adjusting for sociodemographic, lifestyle, and clinical characteristics. We identified 398 dementia cases during follow up (median = 6.1 y). PM_2.5 and NO₂ reduced significantly over the 10 y before baseline. Larger AQ improvement was associated with reduced dementia risks (HR_PM2.5 0.80 per 1.78 μg/m³, 95% CI 0.71–0.91; HR_NO2 0.80 per 3.91 parts per billion, 95% CI 0.71–0.90), equivalent to the lower risk observed in women 2.4 y younger at baseline. Higher PM_2.5 at baseline was associated with higher dementia risk (HR_PM2.5 1.16 per 2.90 μg/m³, 95% CI 0.98–1.38), but the lower dementia risk associated with improved AQ remained after further adjusting for recent exposure. The observed associations did not substantially differ by age, education, geographic region, Apolipoprotein E e4 genotypes, or cardiovascular risk factors. Long-term AQ improvement in late life was associated with lower dementia risk in older women.

Consistent evidence from epidemiologic studies and toxicological experiments has shown that ambient air pollution is an important modifiable risk factor of dementia (1). Several studies have shown an increased risk of dementia associated with late-life exposures to regional fine particulate matter (PM_2.5; with aerodynamic diameter < 2.5 μm) (2–15) and gaseous pollutants (e.g., NO₂; NO_x) (2–4, 11, 12, 15–17) in particular. Over the past 50 y, significant improvements in air quality (AQ) have been observed across the United States because of national policies and strategies aimed at regulating pollution from stationary (power plants; factories) and mobile (vehicles) sources (18). Several US studies have shown that these long-term reductions in air pollution levels are associated with improved lung function (19), decreased bronchitic symptoms (20), lower asthma incidence (21), lengthened life expectancy (22), and reduced mortality (23). However, it remains unclear whether improved AQ also benefits the aging brains.Therefore, we conducted a multiyear study to examine the association between improved AQ and incidence of dementia, which was based on Diagnostic and Statistical Manual of Mental Disorders (Fourth edition) criteria and centrally adjudicated annually (24, 25). We examined data from the Women’s Health Initiative (WHI) Memory Study (WHIMS)—Epidemiology of Cognitive Health Outcomes (WHIMS-ECHO) that included a combined 20 y of data on individual-level outdoor air pollution (1998 to 2012) estimated using regionalized national universal kriging models (26–28) and cognitive function assessed annually (2008 to 2018) in a geographically diverse sample of community-dwelling older women in the United States. We hypothesized that improved AQ over the span of 10 y, as indicated by reductions in PM_2.5 and NO₂ (proxy for traffic pollutants), was associated with lower dementia risk.     

Why are so many biological systems periodic?

The ubiquity of oscillations in biological systems is well established. Oscillations are observed in all types of organisms from the simplest to the most complex. Periods can range from fractions of a second to months or years. From time to time, it has been suggested that many biological oscillations are the result of the breakdown of effective self-regulation. The opposite view is defended here. It is argued that most periodic behavior is not pathological but rather constitutes the normal operation for these systems. They are present because they confer positive functional advantages for the organism. The advantages fall into five general categories: temporal organization, spatial organization, prediction of repetitive events, efficiency and precision of control.     

Orthogonally-polarized excitation for improved two-photon and second-harmonic-generation microscopy,applied to neurotransmitter imaging with GPCR-based sensors

Fluorescent proteins are excited by light that is polarized parallel to the dipole axis of the chromophore. In two-photon microscopy, polarized light is used for excitation. Here we reveal surprisingly strong polarization sensitivity in a class of genetically encoded, GPCR-based neurotransmitter sensors. In tubular structures such as dendrites, this effect led to a complete loss of membrane signal in dendrites running parallel to the polarization direction of the excitation beam. To reduce the sensitivity to dendritic orientation, we designed an optical device that generates interleaved pulse trains of orthogonal polarization. The passive device, which we inserted in the beam path of an existing two-photon microscope, removed the strong direction bias from fluorescence and second-harmonic (SHG) images. We conclude that for optical measurements of transmitter concentration with GPCR-based sensors, orthogonally polarized excitation is essential.     

A bioreactor for studying negative pressure wound therapy on skin grafts

Negative pressure wound therapy (NPWT) has become the prevailing standard of care for treating complex soft tissue wounds and is now being considered for use in alternative applications including improving skin graft take. While it is generally agreed that negative pressure leads to improved wound healing, universal consensus on its optimal application is not supported in the literature. We describe the design and validation of a bioreactor to determine the prospective benefits of NPWT on skin grafts and engineered skin substitutes (ESS). Clinically relevant pressures were applied, and the native human skin was able to withstand greater negative pressures than the engineered substitutes. Both skin types were cultured under static, flow‐only, and −75 mm Hg conditions for 3 days. While it remained intact, there was damage to the epidermal‐dermal junction in the ESS after application of negative pressure. The normal skin remained viable under all culture conditions. The engineered skin underwent apoptosis in the flow‐only group; however, the application of negative pressure reduced apoptosis. Vascular endothelial growth factor levels were significantly higher in the normal flow‐only group, 152.0 ± 75.1 pg/mg protein, than the other culture conditions, 81.6 ± 35.5 pg/mg for the static and 103.6 ± pg/mg for the negative pressure conditions. The engineered skin had a similar trend but the differences were not significant. This bioreactor design can be used to evaluate the impacts of NPWT on the anatomy and physiology of skin to improve outcomes in wounds after grafting with normal or engineered skin.     

Clinical value of cholinesterase in the prediction of biochemical recurrence after radical prostatectomy

Purpose

To evaluate the predictive and prognostic role as well as the clinical impact on decision-making of serum cholinesterase (ChoE) levels in patients treated with radical prostatectomy for clinically nonmetastatic prostate cancer.

Recombinant human tissue-type plasminogen activator is an effective agent for thrombolysis of peripheral arteries and bypass grafts: preliminary report

The efficacy, safety, and effects on hemostasis and coagulation of two doses of human tissue-type plasminogen activator in patients with acute and subacute peripheral arterial occlusion were compared. Seven patients with lower extremity ischemia and one patient with upper extremity ischemia had peripheral arterial thromboses (five arteries, three grafts) confirmed by clinical history, physical examination, and angiography. The duration of occlusion ranged from 31 hours to 30 days (mean 11.9 days). Tissue-type plasminogen activator was infused via a catheter directly into the thrombus at a randomly assigned dose of 0.05 mg/kg/hr (n = 4) or 0.025 mg/kg/hr (n = 4). Thrombolysis was complete in seven patients and partial in one. Duration of infusion ranged from 1 hour to 21 hours (mean 7.4 hours). The low dose required a longer infusion than did the high dose, but they were both successful in achieving thrombolysis. The one patient with partial thrombolysis had abrupt discontinuation of infusion when extravasation through a recently endarterectomized femoral artery developed. Otherwise there were no significant complications from tissue-type plasminogen activator therapy. Secondary procedures to correct underlying arterial disease were performed in five of the seven patients (71%) who had complete thrombolysis. Even at low dosages, infusion of tissue-type plasminogen activator into arteries or bypass graft thrombus produced complete thrombolysis, and no major complications occurred. This allowed more systematic effects to diagnose and treat underlying arterial disease.