Identification and rates of delirium in elderly medical inpatients from diverse language groups

A linguistically diverse cohort of 126 medical inpatients 65 y and over was recruited to determine rates of delirium after admission, associated outcomes, and staff detection of delirium. A clinical interview and cognitive and functional questionnaires were completed with the patient and their carer, and files were reviewed. The incidence of delirium at comprehensive assessment early after admission was 10.3% and the overall incidence 19.1% over the whole admission. Cognitive impairment was common (n = 80, 63.5%), including 61 patients (48.4%) who had dementia. Most patients (83%) with delirium had dementia. Staff recognized less than 21% of patients with delirium, 33% of patients with dementia, and 36% of cognitively impaired patients. There was no difference in outcomes between English and non-English speaking patients. Given the high prevalence and poor recognition of cognitive disorders in older people, routine cognitive screening should occur. Staff education should focus upon improving delirium detection and addressing the needs of cognitively impaired older inpatients.     

A polymorphism in the Irisin-encoding gene (FNDC5) associates with hepatic steatosis by differential miRNA binding to the 3′UTR

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Real-world dosimetric comparison between CyberKnife SBRT and HDR brachytherapy for the treatment of prostate cancer

PurposeHigh-dose-rate (HDR) brachytherapy (BRT) and stereotactic body radiotherapy (SBRT) are currently the two treatment options for definitive radiotherapy of prostate cancer, employing extreme hypofractionation. There are only very few studies comparing their dosimetry, all using computed tomography for treatment planning. We present here a real-word dosimetric comparison between SBRT and ultrasound-based virtual HDR-BRT, with both imaging modalities coming from the same patient.Methods and MaterialsPatients with prostate cancer on a prospective trial evaluating the toxicity of robotic-based SBRT were treated to a total dose of 35 Gy in 5 fractions. Fifteen patients were included in this analysis. During ultrasound-based fiducial implantation, a three-dimensional data set as in real HDR-BRT procedure was acquired. Virtual HDR-BRT plans were generated and various organs at risk and prostate dosimetric parameters were evaluated.ResultsConcerning prostate, SBRT achieved significant higher D₉₈, V₃₅ Gy, and V_37.5 Gy coverage, whereas virtual HDR-BRT achieved significant higher intratumoral doses reflected in the V₄₂ Gy and V_52.5 Gy. Rectal D_max, V₃₆ Gy, and V₂₉ Gy were significantly lower for HDR-BRT with no difference as for V₁₈ Gy. SBRT was significantly inferior regarding bladder dosimetry (D_max, V₃₆ Gy, V₁₈ Gy), whereas urethra D_max and V₄₄ Gy where significantly higher at the expense of HDR-BRT.ConclusionsHDR-BRT is superior regarding rectum and bladder dosimetry, with SBRT being superior relative to urethra dosimetry. A randomized study is warranted to define the best extreme hypofractionated modality.     

Evidence for a role of heat shock protein-90 in toll like receptor 4 mediated pain enhancement in rats

Spinal cord microglial toll-like receptor 4 (TLR4) has been implicated in enhancing neuropathic pain and opposing morphine analgesia. The present study was initiated to explore TLR4-mediated pain modulation by intrathecal lipopolysaccharide, a classic TLR4 agonist. However, our initial study revealed that intrathecal lipopolysaccharide failed to induce low-threshold mechanical allodynia in naive rats, suggestive that TLR4 agonism may be insufficient to enhance pain. These studies explore the possibility that a second signal is required; namely, heat shock protein-90 (HSP90). This candidate was chosen for study given its known importance as a regulator of TLR4 signaling. A combination of in vitro TLR4 cell signaling and in vivo behavioral studies of pain modulation suggest that TLR4-enhancement of neuropathic pain and TLR4-suppression of morphine analgesia each likely require HSP90 as a cofactor for the effects observed. In vitro studies revealed that dimethyl sulfoxide (DMSO) enhances HSP90 release, suggestive that this may be a means by which DMSO enhances TLR4 signaling. While 2 and 100 μg lipopolysaccharide intrathecally did not induce mechanical allodynia across the time course tested, co-administration of 1 μg lipopolysaccharide with a drug that enhances HSP90-mediated TLR4 signaling now induced robust allodynia. In support of this allodynia being mediated via a TLR4/HSP90 pathway, it was prevented or reversed by intrathecal co-administration of a HSP90 inhibitor, a TLR4 inhibitor, a microglia/monocyte activation inhibitor (as monocyte-derived cells are the predominant cell type expressing TLR4), and interleukin-1 receptor antagonist (as this proinflammatory cytokine is a downstream consequence of TLR4 activation). Together, these results suggest for the first time that TLR4 activation is necessary but not sufficient to induce spinally mediated pain enhancement. Rather, the data suggest that TLR4-dependent pain phenomena may require contributions by multiple components of the TLR4 receptor complex.     

Stereotypic behavior of mentally retarded adults adjunctive to a positive reinforcement schedule

Stereotypic behavior is one of the more common disturbed behaviors displayed by people who are developmentally disabled. This study evaluated the indirect effects on stereotypic frequency when the value of a concurrent fixed-interval reinforcement schedule for adaptive behavior was varied. Three profoundly mentally retarded adults performed a simple adaptive task reinforced under a fixed-interval schedule. The reinforcement schedule value was varied from fixed-interval 15 to 90, and 180 seconds after schedule control under each condition was demonstrated. The dependent measure was the frequency of stereotypic behavior. Stereotypic behavior increased in direct relation to the interval length. The theoretical and practical implications of treating stereotypies as an adjunctive behavior partially controlled by the reinforcement frequency for adaptive behaviors are discussed.