Excellent results of cardiac surgery in patients with previous liver transplantation.

Cardiovascular diseases requiring surgical therapy in patients with prior liver transplantation are rare. Little is known about the outcome of patients with liver allograft undergoing cardiac surgery. Herein we report our experience in this patient population with an emphasis on operative outcomes and mid-term survival. Between January 1998 and December 2004, 12 patients (mean +/- standard deviation age 68 +/- 9 years, 7 [58%] male) with previous liver transplantation who underwent cardiac surgery were identified. Main outcome measures were hospital mortality, postoperative complications, allograft function, and long-term survival. There was no in-hospital mortality. Three major complications (25%) occurred, including 1 each (8%) of respiratory failure, renal failure, and biliary leakage. All complications were resolved by the time of discharge. Allograft dysfunction determined by an increase of liver function parameters was noticed in 4 (33%) and recovered before discharge. The average length of stay in intensive care unit was 72 +/- 45 hours, and the mean length of stay in hospital was 22 +/- 17 days. One- and 5-year survival was 91% +/- 8% and 67% +/- 14%, respectively. Cardiac surgery can be performed safely in liver transplant recipients with extremely low mortality and acceptable morbidities. Allograft dysfunction is a common finding, but it is transient, with early functional recovery. Five-year survival of liver recipients undergoing cardiac procedures is similar to that of the general population undergoing cardiac surgery. Our data suggest that these patients should be considered for cardiac surgery in reference centers with expertise in complex cardiac procedures and perioperative management of these highly specific patients.     

Effect of electrical coupling on ionic current and synaptic potential measurements

Recent studies have found electrical coupling to be more ubiquitous than previously thought, and coupling through gap junctions is known to play a crucial role in neuronal function and network output. In particular, current spread through gap junctions may affect the activation of voltage-dependent conductances as well as chemical synaptic release. Using voltage-clamp recordings of two strongly electrically coupled neurons of the lobster stomatogastric ganglion and conductance-based models of these neurons, we identified effects of electrical coupling on the measurement of leak and voltage-gated outward currents, as well as synaptic potentials. Experimental measurements showed that both leak and voltage-gated outward currents are recruited by gap junctions from neurons coupled to the clamped cell. Nevertheless, in spite of the strong coupling between these neurons, the errors made in estimating voltage-gated conductance parameters were relatively minor (<10%). Thus in many cases isolation of coupled neurons may not be required if a small degree of measurement error of the voltage-gated currents or the synaptic potentials is acceptable. Modeling results show, however, that such errors may be as high as 20% if the gap-junction position is near the recording site or as high as 90% when measuring smaller voltage-gated ionic currents. Paradoxically, improved space clamp increases the errors arising from electrical coupling because voltage control across gap junctions is poor for even the highest realistic coupling conductances. Furthermore, the common procedure of leak subtraction can add an extra error to the conductance measurement, the sign of which depends on the maximal conductance.     

Transcranial magnetic stimulation in the treatment of adolescent depression: a systematic review and meta-analysis of aggregated and individual-patient data from uncontrolled studies

Transcranial magnetic stimulation (TMS) is a non-invasive treatment for adolescent major depressive disorder (MDD). Existing evidence on the efficacy of TMS in adolescent MDD awaits quantitative synthesis. A systematic literature search was conducted, and data from eligible studies were synthesized using random-effects models. Treatment-covariate interactions were examined in exploratory analyses of individual-patient data (IPD). Systematic search of the literature yielded 1264 hits, of which 10 individual studies (2 randomized trials) were included for quantitative synthesis of mainly uncontrolled studies. Individual patient data (IPD) were available from five trials (all uncontrolled studies). Quantitative synthesis of aggregated data revealed a statistically significant negative overall standardized mean change (pooled SMCC = 2.04, 95% CI [1.46; 2.61], SE = 0.29, p < .001), as well as a significant overall treatment response rate (Transformed Proportion = 41.30%, 95% CI [31.03; 51.57], SE = 0.05; p < 0.001), considering data from baseline to post-treatment. Exploratory IPD analyses suggests TMS might be more effective in younger individuals and individuals with more severe depression, and efficacy might be enhanced with certain treatment modality settings, including higher number of TMS sessions, longer treatment durations, and unilateral and not bilateral stimulation. Existing studies exhibit methodological shortcomings, including small-study effects and lack of control group, blinding, and randomization—compromising the credibility of the present results. To date, two randomized controlled trials on TMS in adolescent depression have been published, and the only large-scale randomized trial suggests TMS is not more effective than sham stimulation. Future large-scale, randomized, and sham-controlled trials are warranted. Future trials should ensure appropriate selection of patients for TMS treatment and guide precision medicine approaches for stimulation protocols.

     

Distinct synaptic dynamics of heterogeneous pacemaker neurons in an oscillatory network

Many rhythmically active networks involve heterogeneous populations of pacemaker neurons with potentially distinct synaptic outputs that can be differentially targeted by extrinsic inputs or neuromodulators, thereby increasing possible network output patterns. To understand the roles of heterogeneous pacemaker neurons, we characterized differences in synaptic output from the anterior burster (AB) and pyloric dilator (PD) neurons in the lobster pyloric network. These intrinsically distinct neurons are strongly electrically coupled, coactive, and constitute the pyloric pacemaker ensemble. During pyloric oscillations, the pacemaker neurons produce compound inhibitory synaptic connections to the follower lateral pyloric (LP) and pyloric constrictor (PY) neurons, which fire out of phase with AB/PD and with different delay times. Using pharmacological blockers, we separated the synapses originating from the AB and PD neurons and investigated their temporal dynamics. These synapses exhibited distinct short-term dynamics, depending on the presynaptic neuron type, and had different relative contributions to the total synaptic output depending on waveform shape and cycle frequency. However, paired comparisons revealed that the amplitude or dynamics of synapses from either the AB or PD neuron did not depend on the postsynaptic neuron type, LP or PY. To address the functional implications of these findings, we examined the correlation between synaptic inputs from the pacemakers and the burst onset phase of the LP and PY neurons in the ongoing pyloric rhythm. These comparisons showed that the activity of the LP and PY neurons is influenced by the peak phase and amplitude of the synaptic inputs from the pacemaker neurons.     

Potent neutralization of severe acute respiratory syndrome (SARS) coronavirus by a human mAb to S1 protein that blocks receptor association

Effective prophylaxis and antiviral therapies are urgently needed in the event of reemergence of the highly contagious and often fatal severe acute respiratory syndrome (SARS) coronavirus (SARS-CoV) infection. We have identified eight recombinant human single-chain variable region fragments (scFvs) against the S1 domain of spike (S) protein of the SARS-CoV from two nonimmune human antibody libraries. One scFv 80R efficiently neutralized SARS-CoV and inhibited syncytia formation between cells expressing the S protein and those expressing the SARS-CoV receptor angiotensin-converting enzyme 2 (ACE2). Mapping of the 80R epitope showed it is located within the N-terminal 261-672 amino acids of S protein and is not glycosylation-dependent. 80R scFv competed with soluble ACE2 for association with the S1 domain and bound S1 with high affinity (equilibrium dissociation constant, Kd=32.3 nM). A human IgG1 form of 80R bound S1 with a 20-fold higher affinity of 1.59 nM comparable to that of ACE2 (Kd=1.70 nM), and neutralized virus 20-fold more efficiently than the 80R scFv. These data suggest that the 80R human monoclonal antibody may be a useful viral entry inhibitor for the emergency prophylaxis and treatment of SARS, and that the ACE2-binding site of S1 could be an attractive target for subunit vaccine and drug development.     

Mental and personality disorders in infertile women with polycystic ovary: a case-control study

BackgroundPolycystic Ovarian Syndrome (PCOS) is one of the most common causes of infertility in women.ObjectiveThe current study investigated mental and personality disorders in infertile women with and without PCOS.MethodsThis case-control study evaluated 400 infertile women who referred to the Infertility Center in Babol city (North of Iran). Participants were categorized into the case group (201 PCOS) and the control group (199 without PCOS). All of the participants completed the Millon Clinical Multi-axial Inventory-III (MCMI-III).ResultsThe mean scores for clinical personality patterns were significantly higher for six personality disorders (schizoid, avoidant, antisocial, depressive, sadistic, and negativistic) and for three classes of severe personality disorder patterns (schizotypal, borderline, and paranoid) in infertile women with PCOS than in women without PCOS. The mean scores for eight clinical disorders (somatoform, manic disorder, dysthymia, alcohol-dependence, drug-dependence, post-trauma stress disorder, major depression, and delusion disorder) were also higher in infertile women with PCOS than in women without PCOS.ConclusionThe scores of many mental and personality disorders are higher in infertile women with PCOS than in women without PCOS. Thus, clinicians should prioritize recognizing and treating psychological problems of infertile women with PCOS.