Normal sleep and circadian rhythms: neurobiologic mechanisms underlying sleep and wakefulness.

Sleep is a vital, highly organized process regulated by complex systems of neuronal networks and neurotransmitters. Sleep plays an important role in the regulation of central nervous system and body physiologic functions. Sleep architecture changes with age and is easily susceptible to external and internal disruption. Reduction or disruption of sleep can affect numerous functions varying from thermoregulation to learning and memory during the waking state.     

Is part of the molecular basis of the perineurial barrier function the lack of endogenous carbohydrate-binding proteins?

The sugar part of cellular glycoconjugates and specific endogenous sugar receptors, i.e., lectins, can establish a system of biological recognition based on protein-carbohydrate interactions. An assortment of labelled (neo)glycoproteins, carrying different types of sugar moieties, is synthesized to localize respective sugar receptors. With these tools, the histochemical patterns of endogenous carbohydrate-binding receptors of the epi-, peri-, and endoneurium were analyzed in human sural and accessory nerves and in swine sciatic nerve. This approach is complementary to the application of plant lectins, focusing on endogenous carbohydrate-binding proteins (lectins). In contrast to the epi- and endoneurium, which bound certain types of carbohydrates, such endogenous sugar receptors were histochemically not detectable in the perineurial cells. Moreover, no histochemical reaction was present in the "connective tissue septa" localized in the endoneurium in which the endoneurial vessels were embedded. This common property supplies evidence that these septa are composed of perineurial cells. They may represent a barrier in addition to the capillary endothelium. Our observations suggest histogenetical differences between the cell populations of epi- and endoneurium vs. perineurium. This significant difference in the ability to bind carbohydrate residues, conjugated to a carrier protein, is contradictory to the assumption that perineurial cells and fibroblasts are functional variants of the same cell type. The histochemical patterns of endogenous carbohydrate-binding receptors found in human and swine nerves were similar but not identical, with exception of the perineurium, reflecting phylogenetic differences in the expression of sugar-binding proteins. The absence of specific sugar receptors in perineurial cells, however, seems to be a more general phenomenon.(ABSTRACT TRUNCATED AT 250 WORDS)     

Conjunctival epithelial cells from patients with Sjögren's syndrome inappropriately express major histocompatibility complex molecules,La(SSB) antigen,and heat-shock proteins

The La(SSB) antigen has been detected within the cytoplasm and on the membrane of conjunctival cells (CC) from patients with Sjögren's syndrome, whereas it was weakly expressed in the nucleus of normal cells. The diseased CC were shown to overproduce major histocompatibility complex (MHC) class I antigens and express MHC class II antigens. Anti-heat-shock protein monoclonal antibody bound to the cell membrane in patients but not in normal controls.On sabbatical leave from Department of Internal Medicine, Medical School, Ioannina, Greece.     

GABA uptake regulates cortical excitability via cell type-specific tonic inhibition

GABA(A) receptors can mediate both 'phasic' synaptic inhibition and a persistent 'tonic' form of signaling. We show that, in the presence of intact GABA uptake, guinea pig hippocampal interneurons, but not pyramidal cells, express a tonic GABA(A) receptor-mediated conductance. This conductance was pharmacologically distinct from spontaneous inhibitory postsynaptic currents (IPSCs). Inhibiting GABA uptake resulted in the expression of a comparable GABA(A) receptor-mediated tonic conductance in pyramidal cells. Reducing the tonic conductance in interneurons enhanced their excitability and the inhibitory drive to pyramidal cells. These results point to a role for cell type-dependent tonic inhibition in regulating cortical excitability.     

Full-left-full-right split liver transplantation for adult recipients: a systematic review and meta-analysis

Full-left-full-right split liver transplantation (FSLT) for adult recipients, may increase the availability of liver grafts, reduce waitlist time, and benefit recipients with below-average body weight. However, FSLT may lead to impaired graft and patient survival. This study aims to assess outcomes after FSLT. Five databases were searched to identify studies concerning FSLT. Incidences of complications, graft- and patient survival were assessed. Discrete data were pooled with random-effect models. Graft and patient survival after FSLT were compared with whole liver transplantation (WLT) according to the inverse variance method. Vascular complications were reported in 25/273 patients after FSLT (Pooled proportion: 6.9%, 95%CI: 3.1–10.7%, I²: 36%). Biliary complications were reported in 84/308 patients after FSLT (Pooled proportion: 25.6%, 95%CI: 19–32%, I²: 44%). Pooled proportions of graft and patient survival after 3 years follow-up were 72.8% (95%CI: 67.2–78.5, n = 231) and 77.3% (95%CI: 66.7–85.8, n = 331), respectively. Compared with WLT, FSLT was associated with increased graft loss (pooled HR: 2.12, 95%CI: 1.24–3.61, P = 0.006, n = 189) and patient mortality (pooled HR: 1.81, 95%CI: 1.17–2.81, P = 0.008, n = 289). FSLT was associated with high incidences of vascular and biliary complications. Nevertheless, long-term patient and graft survival appear acceptable and justify transplant benefit in selected patients.     

Early variations of circulating interleukin-6 and interleukin-10 levels during thoracic radiotherapy are predictive for radiation pneumonitis.

PURPOSE: To investigate variations of circulating serum levels of interleukin-6 (IL-6), tumor necrosis factor alpha (TNFalpha), and interleukin-10 (IL-10) during three-dimensional conformal radiation therapy (3D-CRT) in patients with non-small-cell lung cancer and correlate these variations with the occurrence of radiation pneumonitis. PATIENTS AND METHODS: Ninety-six patients receiving 3D-CRT for stage I to III disease were evaluated prospectively. Circulating cytokine levels were determined before, every 2 weeks during, and at the end of treatment. Radiation pneumonitis was evaluated prospectively between 6 and 8 weeks after 3D-CRT. The predictive value of clinical, dosimetric, and biologic (cytokine levels) factors was evaluated both in univariate and multivariate analyses. RESULTS: Forty patients (44%) experienced score 1 or more radiation pneumonitis. No association was found between baseline cytokine levels and the risk of radiation pneumonitis. In the whole population, mean levels of TNFalpha, IL-6, and IL-10 remained stable during radiotherapy. IL-6 levels were significantly higher (P = .047) during 3D-CRT in patients with radiation pneumonitis. In the multivariate analysis, covariations of IL-6 and IL-10 levels during the first 2 weeks of 3D-CRT were evidenced as independently predictive of radiation pneumonitis in this series (P = .011). CONCLUSION: Early variations of circulating IL-6 and IL-10 levels during 3D-CRT are significantly associated with the risk of radiation pneumonitis. Variations of circulating IL-6 and IL-10 levels during 3D-CRT may serve as independent predictive factors for this complication.     

Gender-specific Differences in Clinicopathologic Outcomes Following Radical Cystectomy: An International Multi-institutional Study of More Than 8000 Patients

Background

The impact of gender on the staging and prognosis of urothelial carcinoma of the bladder (UCB) is insufficiently understood.

Objective

To assess gender-specific differences in pathologic factors and survival of UCB patients treated with radical cystectomy (RC).

Design, setting, and participants

Data from 8102 patients treated with RC (6497 men [80%] and 1605 women [20%]) for UCB between 1971 and 2012 were analyzed.

Outcome measurements and statistical analysis

Multivariable competing-risk regression analyses were performed to evaluate the relationship of gender on disease recurrence (DR) and cancer-specific mortality (CSM). We also tested the interaction of gender and tumor stage, nodal status, and lymphovascular invasion (LVI).

Results and limitations

Female patients were older at the time of RC (p = 0.033) and had higher rates of pathologic stage T3/T4 disease (p < 0.001). In univariable, but not in multivariable analysis, female gender was associated with a higher risk of DR (p = 0.022 and p = 0.11, respectively). Female gender was an independent predictor for CSM (p = 0.004). We did not find a significant interaction between gender and stage, nodal metastasis, or LVI (all p values >0.05).

Conclusions

We found female gender to be associated with a higher risk of CSM following RC. However, these findings do not appear to be explained by gender differences in pathologic stage, nodal status, or LVI. This gender disparity may be due to differences in care and/or the biology of UCB.