Depressive symptoms predict long-term mortality after liver transplantation

Objective

Depressive symptoms are common after liver transplantation (LT). We studied whether depressive symptoms affect long-term survival after LT.

Methods

In a prospective cohort study, 134 liver transplant patients were assessed for depressive symptoms using the Beck Depression Inventory—short form (BDI), focusing on the 3 months post-LT score and on the score change from the waiting list period. They were followed up for long-term survival. The median duration of the follow-up period was 43 months post-LT. None of the 134 patients was lost to follow-up for survival.

Results

A total of 33.6% of the LT patients had mild to moderate depressive symptoms 3 months post-LT. Eighteen (13.4%) patients died during the follow-up. Using Cox proportional hazards analysis, depressive symptoms were significantly associated with mortality (hazard ratio [HR] 1.22, 95% confidence interval (CI) 1.07-1.40, P<.003), one more point in the BDI score being associated with a 17% increase in mortality risk. Other predictive factors of mortality were older age and hepatitis C virus with recurrence 3 months post-LT. Similarly, an increase in depressive symptoms between the waiting list and 3 months post-LT periods predicted mortality (HR 1.18, 95% CI 1.01-1.38, P=.03), especially for patients without depressive symptoms on waiting list (HR 1.56, 95% CI 1.16-2.12, P=.004).

Conclusion

Depressive symptoms after LT and an increase in depressive symptoms between the waiting list and post-LT are associated with an increased risk of long-term mortality. Interventions that could reduce depressive symptoms could potentially decrease long-term mortality after LT.     

Evidence for Higher Functions of the Cerebellum: Eating and Grooming Elicited by Cerebellar Stimulation in Cats

Well-organized eating and grooming behaviors were elicited in cats by stimulation of a zone in the cerebellum that extended from the fastigial nucleus to the superior cerebellar peduncle. Behaviors appeared to result from the facilitation of specific sensorimotor mechanisms, rather than the induction of generalized "drive" states. The results emphasize the need for a broad view of cerebellar function.     

Bacterially produced HIV-2 env polypeptides specific for distinguishing HIV-2 from HIV-1 infections

Five unique recombinant polypeptides, each encoded by a DNA segment representing a different region of the HIV-2 (NIH-Z strain) env gene, were produced at relatively high levels (greater than or equal to 5%) as cII-fusion products in Escherichia coli. These recombinant polypeptides were characterized serologically by the Western blot assay against a panel of HIV-2 and HIV-1 antibody-positive sera, and with normal human sera (HIV-1 and HIV-2 antibody negative). Only those polypeptides that are encoded by a segment of the env gene from the N-terminal region of the transmembrane protein gp35 (amino acids 537 to 707) were immunoreactive. Three polypeptides (921, 996, and 997), each encoding this immunoreactive region of the HIV-2 (NIH-Z) gp35, reacted strongly and specifically with antibodies in sera from HIV-2-positive individuals, but not with antibodies in sera from HIV-1-positive or HIV-uninfected individuals. These results show that the N-terminal region of the HIV-2 gp35 contains a highly antigenic determinant which is strongly immunogenic in HIV-2-infected individuals. The gp35-encoded recombinant env polypeptides can potentially be used in diagnostic assays to specifically differentiate between HIV-2 and HIV-1 infections.     

The future of disease prevention

The success of curative medical strategies calls attention to a lack in the completeness of health care: disease prevention. Bringing prevention appropriately into health care requires five types of effort: 1) broadening the view of health beyond the medical model to include the environment, social services, and personal health habits; 2) improving the science of prevention; 3) institutionalizing preventive services by relating them to all the participants, from the professionals to the government to the payers to the public; 4) encouraging non-physician health professionals to assume their suitable, possibly majority, share of providing preventive services; and 5) emphasizing preventive services notwithstanding an unevenness of access to them. Received from the Institute of Medicine, 2101 Constitution Avenue, N.W., Washington, DC 20418.     

Interleukin‐10 producing‐B cells and their association with responsiveness to rituximab in myasthenia gravis

Introduction: A subset of regulatory B cells in humans and mice has been defined functionally by their ability to produce interleukin (IL)‐10. We characterized IL‐10‐producing B (B10) cells in myasthenia gravis (MG) patients and correlated them with disease activity and responsiveness to rituximab therapy. Methods: Frequencies of B10 cells from MG patients and healthy controls were monitored by fluorescence‐activated cell sorting (FACS). Results: MG patients had fewer B10 cells than controls, which was associated with more severe disease status. Moreover, patients who responded well to rituximab therapy exhibited rapid repopulation of B10 cells, whereas in patients who did not respond well to rituximab, B10 cell repopulation was delayed. The kinetics of B10 cells were related to the responsiveness to rituximab in MG. Conclusions: We have characterized a specific subset of B10 cells in MG patients which may serve as a marker for disease activity and responsiveness to immune therapy. Muscle Nerve 49:487–494, 2014     

Contribution of the motor system to the perception of reachable space: an fMRI study

The present functional magnetic resonance imaging (fMRI) study investigates the neural correlates of reachability judgements. In a block design experiment, 14 healthy participants judged whether a visual target presented at different distances in a virtual environment display was reachable or not with the right hand. In two control tasks, they judged the colour or the relative position of the visual target according to flankers. Contrasting the activations registered in the reachability judgement task and in the control tasks, we found activations in the frontal structures, and in the bilateral inferior and superior parietal lobe, including the precuneus, and the bilateral cerebellum. This fronto‐parietal network including the cerebellum overlaps with the brain network usually activated during actual motor production and motor imagery. In a following event‐related design experiment, we contrasted brain activations when targets were rated as ‘reachable’ with those when they were rated as ‘unreachable’. We found activations in the left premotor cortex, the bilateral frontal structures, and the left middle temporal gyrus. At a lower threshold, we also found activations in the left motor cortex, and in the bilateral cerebellum. Given that reaction time increased with target distance in reachable space, we performed a subsequent parametric analysis that revealed a related increase of activity in the fronto‐parietal network including the cerebellum. Unreachable targets did not show similar activation, and particularly in regions associated to motor production and motor imagery. Taken together, these results suggest that dynamical motor representations used to determine what is reachable are also part of the perceptual process leading to the distinct representation of peripersonal and extrapersonal spaces.     

Comparison of the relative toxicities of Shiga-like toxins type I and type II for mice.

In earlier studies using a streptomycin-treated mouse model of infection caused by enterohemorrhagic Escherichia coli (EHEC), animals fed Shiga-like toxin type II (SLT-II)-producing strains developed acute renal cortical necrosis and died, while mice fed Shiga-like toxin type I (SLT-I)-producing clones did not die (E. A. Wadolkowski, L. M. Sung, J. A. Burris, J. E. Samuel, and A. D. O'Brien, Infect. Immun. 58:3959-3965, 1990). To examine the bases for the differences we noted between the two toxins in the murine infection model, we injected mice with purified toxins and carried out histopathological examinations. Despite the genetic and structural similarities between the two toxins, SLT-II had a 50% lethal dose (LD50) which was approximately 400 times lower than that of SLT-I when injected intravenously or intraperitoneally into mice. Histopathologic examination of toxin-injected mice revealed that detectable damage was limited to renal cortical tubule epithelial cells. Passive administration of anti-SLT-II antibodies protected mice from SLT-II-mediated kidney damage and death. Immunofluorescence staining of normal murine kidney sections incubated with purified SLT-I or SLT-II demonstrated that both toxins bound to cortical tubule and medullary duct epithelial cells. Compared with SLT-I, SLT-II was more heat and pH stable, suggesting that SLT-II is a relatively more stable macromolecule. Although both toxins bound to globotriaosylceramide, SLT-I bound with a higher affinity in a solid-phase binding assay. Differences in enzymatic activity between the two toxins were not detected. These data suggest that structural/functional differences between the two toxins, possibly involving holotoxin stability and/or receptor affinity, may contribute to the differential LD50s in mice.     

The involvement of CD14 in stimulation of cytokine production by uronic acid polymers

In this study the molecular mechanisms behind the stimulatory activities of the uronic acid polymers poly mannuronic acid (poly M), high M alginate and oxidized cellulose (C60XY) were investigated and compared with lipopolysaccharide (LPS). The cytokine-inducing abilities of the uronic acid polymers and LPS were examined on CD14-positive human monocytes and CD14-negative U373 astrocytoma cells. It was found that LPS induced monocytes and U373 cells to produce tumor necrosis factor (TNF) and interleukin(IL)-6, respectively, by different mechanisms. The poly uronic acids induced monocytes to produce TNF, but with 100-1000 times less potency compared to LPS. On U373 cells, LPS at concentrations ? 32 ng/ml resulted in a dose-related IL-6 production, whereas the poly uronic acids had negligible effects even at 1 mg/ml. The binding data demonstrate that only the CD14-positive monocytes in the peripheral blood mononuclear cells population bound poly M. Furthermore, poly M was found to bind to CD14 in the presence of serum. Antibodies against CD14 also inhibited the TNF-inducing activity of the three uronic acid polymers tested. In conclusion, these results demonstrate that uronic acid polymers induce TNF production through mechanisms which involve CD 14.     

Power spectral analysis of the electroencephalographic and hemodynamic correlates of propofol anesthesia in the rat: Intravenous infusion

Based on the tail-flick response to noxious thermal stimuli, we determined in the present study that effective antinociception could be achieved in adult male Sprague-Dawley rats 15 min after intravenous infusion of propofol at 60 mg/kg/h. Simultaneous power spectral analysis of the electroencephalographic (EEG) and systemic arterial pressure signals further revealed a concomitant depression of the activity of all EEG frequency bands (δ, θ, , β), alongside hypotension, negative inotropic and chronotropic actions, and attenuated baroreceptor reflex and vasomotor activity. These effects were congruent with a plasma concentration of propofol in the arterial blood of 1.70 ± 0.13 μg/ml, as determined by high-performance liquid chromatography.     

Mechanical properties of experimental dental composites containing a combination of mesoporous and nonporous spherical silica as fillers

ObjectivesMesoporous fillers have been investigated for use in dental composites because of their potential for creating micromechanical filler/resin matrix interphase bonding. Such a micromechanical bonding could eliminate the need for the silane treatment of fillers for interfacial chemical bonding that is prone to hydrolysis in the oral environment. In the case of micromechanical bonding, dental polymer chains are threaded mechanically (like a “necklace”) through nanosized channels in the fillers.MethodsA combination of mesoporous silica, which was synthesized using the non-surfactant templating method, and nonporous spherical silica (500 nm) was used to prepare experimental dental composites. The porous silica used in this study contained interconnected pores and channels as opposed to porous fillers containing surface pores. The compressive strength, compressive modulus, flexural modulus, and flexural strength of these composites were evaluated.ResultsThe results showed that composites containing a combination of mesoporous and nonporous fillers have better mechanical properties than the composites having either of these fillers alone.SignificanceThe results showed that a combination of mesoporous and nonporous materials can be used to prepare stronger dental materials that may resist hydrolysis and wear.