Selective prevention of combat-related post-traumatic stress disorder using attention bias modification training: a randomized controlled trial.

BACKGROUND: Efficacy of pre-trauma prevention for post-traumatic stress disorder (PTSD) has not yet been established in a randomized controlled trial. Attention bias modification training (ABMT), a computerized intervention, is thought to mitigate stress-related symptoms by targeting disruptions in threat monitoring. We examined the efficacy of ABMT delivered before combat in mitigating risk for PTSD following combat. METHOD: We conducted a double-blind, four-arm randomized controlled trial of 719 infantry soldiers to compare the efficacy of eight sessions of ABMT (n = 179), four sessions of ABMT (n = 184), four sessions of attention control training (ACT; n = 180), or no-training control (n = 176). Outcome symptoms were measured at baseline, 6-month follow-up, 10 days following combat exposure, and 4 months following combat. Primary outcome was PTSD prevalence 4 months post-combat determined in a clinical interview using the Clinician-Administered PTSD Scale. Secondary outcomes were self-reported PTSD and depression symptoms, collected at all four assessments. RESULTS: PTSD prevalence 4 months post-combat was 7.8% in the no-training control group, 6.7% with eight-session ABMT, 2.6% with four-session ABMT, and 5% with ACT. Four sessions of ABMT reduced risk for PTSD relative to the no-training condition (odds ratio 3.13, 95% confidence interval 1.01-9.22, p < 0.05, number needed to treat = 19.2). No other between-group differences were found. The results were consistent across a variety of analytic techniques and data imputation approaches. CONCLUSIONS: Four sessions of ABMT, delivered prior to combat deployment, mitigated PTSD risk following combat exposure. Given its low cost and high scalability potential, and observed number needed to treat, research into larger-scale applications is warranted. The ClinicalTrials.gov identifier is NCT01723215.

Concanavalin A modulates a potassium channel in cultured Aplysia neurons.

A novel 100 pS K(+)-selective ion channel is frequently observed in cell-attached membrane patches from cultured Aplysia neurons. The activity of this channel is moderately voltage-dependent, but channel openings are rare and brief even when the patch is strongly depolarized. However, the activity of the channel is increased dramatically by the addition of the lectin concanavalin A (Con A), to the patch pipette. The channel is also activated by Con A in the bathing medium, suggesting that the lectin's action is via an as yet unidentified intracellular second messenger. In the one single-channel patch studied, Con A had no effect on the channel mean open time; rather it decreased the average duration of the long closed times between bursts of openings. Thus Con A increases either the open probability of single channels, the number of functional channels in the patch, or both. The functional significance of the Con A-induced modulation of K+ channel activity remains to be determined.

A dynamically regulated 14-3-3, Slob, and Slowpoke potassium channel complex in Drosophila presynaptic nerve terminals.

Slob is a novel protein that binds to the carboxy-terminal domain of the Drosophila Slowpoke (dSlo) calcium-dependent potassium (K(Ca)) channel. A yeast two-hybrid screen with Slob as bait identifies the zeta isoform of 14-3-3 as a Slob-binding protein. Coimmunoprecipitation experiments from Drosophila heads and transfected cells confirm that 14-3-3 interacts with dSlo via Slob. All three proteins are colocalized presynaptically at Drosophila neuromuscular junctions. Two serine residues in Slob are required for 14-3-3 binding, and the binding is dynamically regulated in Drosophila by calcium/calmodulin-dependent kinase II (CaMKII) phosphorylation. 14-3-3 coexpression dramatically alters dSlo channel properties when wild-type Slob is present but not when a double serine mutant Slob that is incapable of binding 14-3-3 is present. The results provide evidence for a dSlo/Slob/14-3-3 regulatory protein complex.

Slob, a novel protein that interacts with the Slowpoke calcium-dependent potassium channel.

Slob, a novel protein that binds to the carboxy-terminal domain of the Drosophila Slowpoke (dSlo) calcium-dependent potassium channel, was identified with a yeast two-hybrid screen. Slob and dSlo coimmunoprecipitate from Drosophila heads and heterologous host cells, suggesting that they interact in vivo. Slob also coimmunoprecipitates with the Drosophila EAG potassium channel but not with Drosophila Shaker, mouse Slowpoke, or rat Kv1.3. Confocal fluorescence microscopy demonstrates that Slob and dSlo redistribute in cotransfected cells and are colocalized in large intracellular structures. Direct application of Slob to the cytoplasmic face of detached membrane patches containing dSlo channels leads to an increase in channel activity. Slob may represent a new class of multi-functional channel-binding proteins.

Cross-View Neuroimage Pattern Analysis in Alzheimer's Disease Staging.

The research on staging of pre-symptomatic and prodromal phase of neurological disorders, e.g., Alzheimer's disease (AD), is essential for prevention of dementia. New strategies for AD staging with a focus on early detection, are demanded to optimize potential efficacy of disease-modifying therapies that can halt or slow the disease progression. Recently, neuroimaging are increasingly used as additional research-based markers to detect AD onset and predict conversion of MCI and normal control (NC) to AD. Researchers have proposed a variety of neuroimaging biomarkers to characterize the patterns of the pathology of AD and MCI, and suggested that multi-view neuroimaging biomarkers could lead to better performance than single-view biomarkers in AD staging. However, it is still unclear what leads to such synergy and how to preserve or maximize. In an attempt to answer these questions, we proposed a cross-view pattern analysis framework for investigating the synergy between different neuroimaging biomarkers. We quantitatively analyzed nine types of biomarkers derived from FDG-PET and T1-MRI, and evaluated their performance in a task of classifying AD, MCI, and NC subjects obtained from the ADNI baseline cohort. The experiment results showed that these biomarkers could depict the pathology of AD from different perspectives, and output distinct patterns that are significantly associated with the disease progression. Most importantly, we found that these features could be separated into clusters, each depicting a particular aspect; and the inter-cluster features could always achieve better performance than the intra-cluster features in AD staging.

Transient and long-term effects of temperature on electrogenic activity of Drosophila nerves and muscles.

Electrical responses of indirect flight muscles in Drosophila fruit flies are markedly affected by a 10 degree C increment from ambient temperature: refractory period of evoked neuromuscular responses is shortened with temperature elevation due to effects on neuronal components. Excitation threshold of these muscle fibers increases transiently during elevation of temperature, while the frequency of directly-evoked muscle spikes increases gradually. These temperature-induced changes are reversible upon lowering the temperature back to ambient temperature.

Inactivating and non-inactivating outward current channels in cell-attached patches of Helix neurons.

Two species of inactivating outward current channels and a non-inactivating voltage-dependent current were seen in cell-attached patches of Helix neurons. Large, slowly inactivating channels had a slope conductance of 44 pS as measured with patch pipets containing the normal extracellular ion concentrations, including 4 mM potassium. Latency to maximal opening was 50-220 ms, and the inactivation time constant averaged 350 ms. Channel opening was decreased by preceding depolarization. The channels were selective for potassium and inhibited by 50 mM TEA. Small, quickly inactivating channels were 14 pS and had kinetics and voltage dependence similar to IA. Patch depolarization also activated a non-inactivating voltage-dependent outward current having channel conductance and/or kinetics such that individual channel openings and closings could not be distinguished. Such current was also seen in the presence of 50 mM TEA, but not in the presence of Co2+, characteristics which are similar to outward hydrogen ion currents, described by others in Helix neurons.

Triplicated bursting neuron R15 in an Aplysia abdominal ganglion: non-symmetrical coupling, common synaptic inputs and response to dopamine.

An abdominal ganglion of the mollusc Aplysia californica was found to contain 3 neurons in the place normally occupied by a single R15 cell. The 3 neurons exhibited properties characteristic of R15 neurons including spontaneous bursts. The bursts appeared asynchronously in spite of electrotonic coupling between them. The coupling function approximated a low pass filter with a cut-off frequency between 0.02 and 0.05 Hz in accordance with a measured coupling time-constant of 5--10 sec. Coupling measured in the cell body was found to be stronger for hyperpolarizing currents than for depolarizing currents injected into any of the 3 cells. This 'symmetrical rectification' can be explained by a rectifying axonal membrane interposed between the site of coupling and the site of recording. All 3 cells were found to have dopamine receptors and to receive common synaptic inputs. Since the coupling efficiency was found to vary depending on the direction of current flow, depolarizing synaptic inputs and spike burst generation remain autonomous.

Na(+)-activated K+ channels are widely distributed in rat CNS and in Xenopus oocytes.

We recorded the activity of K+ channels activated by sodium (KNa channels) in two widely used preparations, primary cell cultures prepared from neocortex, cerebellum, midbrain, brainstem and spinal cord, and Xenopus oocytes. KNa channels from all regions shared an absolute dependence on [Na+], had conductances of 140-170 pS in symmetrical 150 mM K+ and exhibited characteristic substates. The role of this channel must now be considered in terms of its widespread distribution.

Single-trabecula building block for large-scale finite element models of cancellous bone.

Recent development of high-resolution imaging of cancellous bone allows finite element (FE) analysis of bone tissue stresses and strains in individual trabeculae. However, specimen-specific stress/strain analyses can include effects of anatomical variations and local damage that can bias the interpretation of the results from individual specimens with respect to large populations. This study developed a standard (generic) 'building-block' of a trabecula for large-scale FE models. Being parametric and based on statistics of dimensions of ovine trabeculae, this building block can be scaled for trabecular thickness and length and be used in commercial or custom-made FE codes to construct generic, large-scale FE models of bone, using less computer power than that currently required to reproduce the accurate micro-architecture of trabecular bone. Orthogonal lattices constructed with this building block, after it was scaled to trabeculae of the human proximal femur, provided apparent elastic moduli of approximately 150 MPa, in good agreement with experimental data for the stiffness of cancellous bone from this site. Likewise, lattices with thinner, osteoporotic-like trabeculae could predict a reduction of approximately 30% in the apparent elastic modulus, as reported in experimental studies of osteoporotic femora. Based on these comparisons, it is concluded that the single-trabecula element developed in the present study is well-suited for representing cancellous bone in large-scale generic FE simulations.

Twenty-one years of monitoring congenital malformations (1974-1994): The Israel Birth Defects Monitoring System, affiliated with the International Clearinghouse.

The first 21 years of monitoring of congenital malformations by a hospital-based program affiliated to the International Clearinghouse is analyzed. The foundation activities, methodology, data and time trends are presented and precautions in interpretation of this information are emphasized. The great majority of congenital malformations, including Down syndrome, have stable rates making the search of their causes and the development of intervention methods much harder. The practical implications of these data and the appropriate recommendations are discussed.

Lung nodule classification with multilevel patch-based context analysis.

In this paper, we propose a novel classification method for the four types of lung nodules, i.e., well-circumscribed, vascularized, juxta-pleural, and pleural-tail, in low dose computed tomography scans. The proposed method is based on contextual analysis by combining the lung nodule and surrounding anatomical structures, and has three main stages: an adaptive patch-based division is used to construct concentric multilevel partition; then, a new feature set is designed to incorporate intensity, texture, and gradient information for image patch feature description, and then a contextual latent semantic analysis-based classifier is designed to calculate the probabilistic estimations for the relevant images. Our proposed method was evaluated on a publicly available dataset and clearly demonstrated promising classification performance.

New technique for movement analysis: application to biological systems.

A new system for motion analysis is described. Modulation of light intensity of an organism's movement over an opaque and transparent checkerboard grid is monitored by a photocell. The photocell's output is proportional to the organism's amplitude and frequency of movement. This output is analyzed by a continuous interval dot display and spectrum analysis. The system was tested by analyzing the activity of 4 Drosophila strains which are known to differ in their activity. General applicability of the system is discussed.

Calcium current in growth balls from isolated Helix aspersa neuronal growth cones.

Growth cones were severed from their neurites in primary cultures of Helix aspersa neurons. Following isolation, growth cones rolled up into 5-10-micron-diameter spheres, which remained attached to a poly-L-lysine or lectin-coated glass coverslip. Whole-cell-configuration patch-clamp recordings from isolated growth cones revealed inward calcium currents upon block of outward currents with internally perfused CsCl. Up to 50 microM tetrodotoxin did not affect this current. In 20-micron-diameter spheres, a peak current of 1.2 nA was reached within 3 ms under voltage-clamp conditions for a 60-mV pulse from a holding potential of -50 mV. Channel density calculations averaged to approximately one channel per square micrometer. A two-phase inactivation was evident under voltage-clamp steps from -50 mV to +15 mV. The growth balls described can be internally perfused and voltage clamped to measure ionic currents involved in growth cone function.

A novel cGMP-activated Cl- channel in renal proximal tubules.

Cl- channels activated by natriuretic peptides were detected in cultured rat proximal convoluted tubule (PCT) cells with the use of patch-clamp methodology. Bath application of atrial natriuretic peptide (ANP) activates a 150-pS Cl- channel with the open probability (Po) of the channel increasing from 0.0008 +/- 0.0003 to 0.021 +/- 0.008. 8-Bromoguanosine 3',5'-cyclic monophosphate (8-BrcGMP), a membrane-permeable analogue of cGMP, increased channel activity in the on-cell mode. In inside-out patches the channel was activated by cGMP in a dose-dependent manner. Channel activity decreased after washing out and increased on reapplication of cGMP. A similar activation was observed also in presence of either of two protein kinase inhibitors, N-[2-(methylamino)ethyl]-5-isoquinolinesulfonamide dihydrochloride or KT5823, or a phosphatase inhibitor. Bath application of urodilatin mimicked the action of ANP. Po of the channel was found to be independent of both voltage and Ca2+, and gating activity could be blocked by the stilbene, 4,4-dinitrostilbene-2,2-disulfonic acid. These results demonstrate a Cl- conductance in PCT cells modulated by ANP and urodilatin via their second messenger, cGMP.

Diverse modulations of chloride channels in renal proximal tubules.

Cl- selective channels were detected and characterized in apical membranes of cultured rat renal proximal convoluted tubule cells (PCT) using patch-clamping methods. Subpopulations of Cl- channels modulated by cyclic nucleotides, Ca2+, or voltage were identified. Two different 30-pS, voltage-independent, Cl- channels modulated by adenosine 3',5'-cyclic monophosphate (cAMP) or Ca2+ were seen most frequently. The cAMP-dependent channel was activated by membrane-permeable analogues of cAMP, dibutyryl-cAMP or 8-bromo-cAMP. Catalytic subunit of protein kinase A (PKA) applied to detached inside-out patches, activated the channel as well, suggesting activation via phosphorylation. Channel activity was blocked by 4,4'-diisothiocyanostilbene-2,2'-disulfonic acid, by 4,4-dinitrostilbene-2,2-disulfonic acid, and by SCN-. Permeability sequence for different halides was Cl- > I > F with a Cl(-)-to-cation permeability ratio (PCl/Pcation) of 7:1. The Ca(2+)-sensitive channel was not activated by cAMP nor by PKA. A third anionic selective channel encountered infrequently is voltage dependent and has a unitary conductance of 145 pS, with a PCl/Pcation value of 9:1. This diversity of Cl- channels may underlie the rich repertoire of physiological functions attributed to Cl- channels.