A previous study reported the increased expression of the cytokine TNF in the adipose tissue of genetically obese rodents. To examine this paradigm in humans, we studied TNF expression in lean, ...obese, and reduced-obese human subjects. TNF mRNA was demonstrated in human adipocytes and adipose tissue by Northern blotting and PCR. TNF protein was quantitated by Western blotting and ELISA in both adipose tissue and the medium surrounding adipose tissue. Using quantitative reverse transcriptase PCR (RT-PCR), TNF mRNA levels were examined in the adipose tissue of 39 nondiabetic subjects, spanning a broad range of body mass index (BMI). There was a significant increase in adipose TNF mRNA levels with increasing adiposity. There was a significant correlation between TNF mRNA and percent body fat (r = 0.46, P < 0.05, n = 23). TNF mRNA tended to decrease in very obese subjects, but when subjects with a BMI > 45 kg/m2 were excluded, there was a significant correlation between TNF mRNA and BMI (r = 0.37, P < 0.05, n = 32). In addition, there was a significant decrease in adipose TNF with weight loss. In 11 obese subjects who lost between 14 and 66 kg (mean 34.7 kg, or 26.6% of initial weight), TNF mRNA levels decreased to 58% of initial levels after weight loss (P < 0.005), and TNF protein decreased to 46% of initial levels (P < 0.02). TNF is known to inhibit LPL activity. When fasting adipose LPL activity was measured in these subjects, there was a significant inverse relationship between TNF expression and LPL activity (r = -0.39, P < 0.02, n = 39). With weight loss, LPL activity increased to 411% of initial levels. However, the magnitude of the increase in LPL did not correlate with the decrease in TNF. Thus, TNF is expressed in human adipocytes. TNF is elevated in most obese subjects and is decreased by weight loss. In addition, there is an inverse relationship between TNF and LPL expression. These data suggest that endogenous TNF expression in adipose tissue may help limit obesity in some subjects, perhaps by increasing insulin resistance and decreasing LPL.
Operative endoscopy and flexible fiber-optic in-office tissue biopsy are common techniques to assess suspicious laryngopharyngeal lesions.
The primary outcome was the delay to the initiation of ...treatment. Secondary outcomes were delay to biopsy, histopathological diagnosis, and assessment at a multidisciplinary oncology clinic. A retrospective analysis was performed to assess the relative delays between these approaches to biopsy of laryngopharyngeal lesions.
There were 114 patients in the study cohort; 44 in-office and 70 operative endoscopic biopsies). The mean delay from consultation to biopsy was 17.4 days for the operative endoscopy group and 1.3 days for the in-office group. The mean delay from initial otolaryngology consultation to initiation of treatment was 51.7 days and 44.6 days for the operative endoscopy and in-office groups, respectively.
In-office biopsy reduced the time from initial consultation to biopsy. The temporal gains via in-office biopsy did not translate into faster access to treatment. This outcome highlights the opportunity to improve access to treatment for patients with early diagnosis.
Abstract Objective To assess the effects of second generation antipsychotics on neurocognitive function in patients with stable remission of first episode psychosis. Methods Fifty-three patients with ...first onset psychosis in the schizophrenia spectrum entered a randomised controlled trial of guided discontinuation (GD) versus maintenance treatment (MT) with second generation antipsychotics. A comprehensive neurocognitive test battery was administered at the time of remission and shortly after dose reduction or discontinuation (GD-group) or at the same time in the MT-group. Results With the exception of negative symptoms, PANSS scores decreased over time and neurocognition improved significantly on most tests in both groups. The GD-group, however, improved significantly more than the MT-group on three neurocognitive measures in the domain of speed of processing. Conclusion These data suggest that, in first episode patients, dose reduction or discontinuation of second generation antipsychotics after stable remission is achieved, might improve neurocognitive function more than continuing second generation antipsychotics, suggesting a negative role for second generation antipsychotics, specifically in the domain of speed of processing.
OBJECTIVES:Therapies to achieve sustained antiretroviral therapy-free HIV remission will require validation in analytic treatment interruption (ATI) trials. Identifying biomarkers that predict time ...to viral rebound could accelerate the development of such therapeutics.
DESIGN:A pooled analysis of participants from six AIDS Clinical Trials Group ATI studies to identify predictors of viral rebound.
METHODS:Cell-associated DNA (CA-DNA) and CA-RNA were quantified in pre-ATI peripheral blood mononuclear cell samples, and residual plasma viremia was measured using the single-copy assay.
RESULTS:Participants who initiated antiretroviral therapy (ART) during acute/early HIV infection and those on a non-nucleoside reverse transcriptase inhibitor-containing regimen had significantly delayed viral rebound. Participants who initiated ART during acute/early infection had lower levels of pre-ATI CA-RNA (acute/early vs. chronic-treatedmedian <92 vs. 156 HIV-1 RNA copies/10 CD4 cells, P < 0.01). Higher pre-ATI CA-RNA levels were significantly associated with shorter time to viral rebound (≤4 vs. 5–8 vs. >8 weeksmedian 182 vs. 107 vs. <92 HIV-1 RNA copies/10 CD4 cells, Kruskal–Wallis P < 0.01). The proportion of participants with detectable plasma residual viremia prior to ATI was significantly higher among those with shorter time to viral rebound.
CONCLUSION:Higher levels of HIV expression while on ART are associated with shorter time to HIV rebound after treatment interruption. Quantification of the active HIV reservoir may provide a biomarker of efficacy for therapies that aim to achieve ART-free HIV remission.
The aim of this study was to assess the incidence and outcome of procedure-related rupture of intracranial aneurysms in patients treated with Guglielmi detachable coils (GDCs) and to identify risk ...factors for this complication.
Procedure-related rupture occurred in seven of 264 treated aneurysms in 239 consecutive patients. Aneurysm size, history of previous subarachnoid hemorrhage (SAH) caused by the treated aneurysm, timing of treatment after SAH, and the use of a temporary occlusion balloon in the seven procedures in which rupture occurred were compared with the remaining 257 procedures, and these findings were correlated with data from 13 studies in the literature, in which results of 2030 aneurysm treatments were reported.
Procedure-related rupture of intracranial aneurysms during GDC treatment occurs in 2.5% of cases and is responsible for 1% of treatment-related deaths. Risk factors are as follows: small aneurysm size, previous SAH, and probably the use of a temporary occlusion balloon.
We studied interactions of genetic and environmental factors shaping adult emotionality and stress coping, and tested the hypothesis that repeated periodic maternal deprivation (PMD) exerts ...differential effects on adult behavioral and neuroendocrine stress responsiveness in dependence on the genetic predisposition to either hyper- or hypo-anxiety. Exposure of male Wistar rats bidirectionally bred for either high (HAB) or low (LAB) anxiety-related behavior to PMD between postnatal days 2 and 15 resulted in a behavioral approximation of the selected lines. This was reflected by test-dependent signs of reduced anxiety-related behavior in adult HAB rats and of enhanced levels of anxiety in LAB rats compared with their corresponding unstressed controls. In addition to behavioral parameters, differential effects of PMD were also seen with respect to the responsiveness of the hypothalamo—pituitary—adrenocortical axis to acute stressor exposure (novel environment) in adulthood. The corticotrophin (ACTH) and corticosterone hyper-responses seen in control rats of the HAB line compared with those of the LAB line became attenuated in PMD-HAB rats, whereas PMD did not significantly alter neuroendocrine responses in LAB rats. Thus, as a result of PMD, both ACTH and corticosterone responses became indistinguishable between HAB and LAB rats. Although HAB dams spent more time on the nest with the litter compared with LAB dams during the first 5 days postpartum, licking and grooming behavior did not differ between the lines prior to separation, and was found to be increased to the same extent in both HAB and LAB dams during the first hour immediately after reunion with the pups. In contrast to early life stress, exposure of adult HAB and LAB rats to a 10-day unpredictable stress schedule failed to alter their emotional measures. The mitigating effect of PMD on both behavioral and neuroendocrine parameters in rats representing extremes in trait anxiety might reflect an evolutionary benefit as the genetic variability among individuals of a species is sustained while allowing adequate responses to potentially dangerous stimuli in adulthood dependent on early life conditions.
To describe how systemic disease is treated in a large cohort of Spanish patients with primary Sjögren syndrome (pSS) in daily practice, focusing on the adequacy of therapies for the level of ...systemic activity measured by ESSDAI score.
By December 2014, our database included 1120 consecutive patients who fulfilled the 2002 classification criteria for SS. Therapeutic schedules were classified into 4 categories: no systemic therapies, hydroxychloroquine (HCQ) and/or low dose glucocorticoids (GCS) (<20mg/day), high dose GCS (>20mg/day) and use of second-line therapies (immunosuppressive agents, intravenous immunoglobulins IVIG and/or rituximab RTX).
There were 1048 (94%) women and 72 (6%) men , with a mean age at diagnosis of 54 years. The main drug-based therapeutic approaches for systemic pSS during follow-up were HCQ in 282 (25%) patients, GCS in 475 (42%, at doses >20mg/day in 255—23%), immunosuppressive agents in 148 (13%), IVIG in 25 (2%) and RTX in 35 (3%) patients. HCQ was associated with a lower risk of death (adjusted HR of 0.57, 95% 0.34–0.95). We classified 16 (7%) of the 255 patients treated with >20mg GCS and 21/148 (14%) treated with immunosuppressive agents as patients inadequately treated, mainly associated with articular involvement of low/moderate activity.
The management of pSS should be organ-specific, using low dose GCS in patients with moderate systemic activity, limiting the use of high dose GCS and second-line therapies to refractory or potentially severe scenarios. The use of systemic therapies for dryness, chronic pain or fatigue is not warranted.
•Nearly half of our patients with pSS received systemic therapies.•The use of HCQ was associated with a lower risk of death.•The management of pSS should be organ-specific.•High dose GCS and second-line therapies should be limited to refractory or potentially-severe clinical scenarios.•The use of systemic therapies for dryness, chronic pain or fatigue is not warranted.
Abstract
Purpose of the Study
Behavioral and psychological symptoms of dementia (BPSD) affect quality of life for people with dementia. Nonpharmacological interventions are the preferred first line ...of treatment, and it is theorized that BPSD are directly influenced by sensory imbalance and improved by sensory equilibrium. The purpose of this article is to investigate the evidence regarding the use of multisensory environments (MSEs) as treatment for BPSD.
Design and Methods
A systematic literature review was performed using the PICO framework within PsycINFO, Web of Science, ERIC, PubMED, and Cinahl databases, as well as additional hand-searched documents. Included articles were published during 1990 to 2015 and report empirical studies of MSE BPSD interventions that include furniture, fixtures, and equipment to provide visual, auditory, tactile, and olfactory stimulation. Desired elements include ergonomic vibroacoustic furniture, bubble tubes, color-changing lights, and fiber optics.
Results
Twelve articles met the inclusion criteria for review. Evidence supports the positive impact of sensory stimulation as a nonpharmacological behavioral treatment for dementia. Many studies investigated both behavior and mood, and several investigated biomedical parameters including heart rate and cognition. Significant differences were not found in the between-group studies when MSE was compared with other one-to-one interventions. Results on long-term effects were mixed. Variations can be seen in terms of research methods, types of environmental interventions, duration, and specific characteristics of participants, thus confounding the reliability of findings.
Implications
Key findings and directions for future research are discussed including primary outcomes, study design, environmental intervention types, and relevant assessment tools.
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