Derivation of the SPAN, a brief diagnostic screening test for post-traumatic stress disorder

The Davidson Trauma Scale (DTS) is a validated 17-item self-rating scale used in the diagnosis of post-traumatic stress disorder (PTSD), which is sensitive to the effects of treatment. It was felt that a shorter version of the scale might provide a better diagnostic screening tool. Subjects were drawn from a sample of 243 patients obtained from multiple cohorts that included a group of survivors of various forms of trauma, including natural disaster, rape and combat. All subjects had diagnostic assessments for PTSD with a clinical interview and completed the DTS. The data were randomly divided between two subsamples, and frequency and severity scores were calculated for the DTS. A four-item scale, the SPAN (named for its top four items: Startle, Physiological arousal, Anger, and Numbness), was developed. It demonstrated an efficiency of 0.88, sensitivity of 0.84, specificity of 0.91 and positive likelihood ratio of 9.1. In a replication sample, values were slightly lower but still acceptable (efficiency = 0.80). A subgroup of PTSD patients received either fluoxetine or placebo in a clinical trial, and a significant SPAN score improvement was observed on fluoxetine. The SPAN, which correlated significantly with the Impact of Events Scale, the Sheehan Disability Scale, and the Structured Interview of PTSD, was found to have a diagnostic accuracy of 88%.     

The involvement of the mediodorsal nucleus of the thalamus and the midbrain extrapyramidal area in locomotion elicited from the ventral pallidum

Motor activity is regulated by projections from the nucleus accumbens to the ventral pallidum, but it is unclear which efferents regulate behavioral output from the ventral pallidum. Motor activity was elicited pharmacologically by microinjecting either the mu opioid receptor agonist, Tyr-D-Ala-Gly-NmePhe-Gly-OH (DAMGO) or the glutamate receptor agonist, alpha-amino-3-hydroxy-5-methyl-4-isoxazole-propionate (AMPA) into the ventral pallidum. The involvement of efferent projections was determined by microinjecting the local anesthetic procaine into the mediodorsal nucleus of the thalamus (MD) or the midbrain extrapyramidal area (MEA) prior to administering DAMGO or AMPA into the ventral pallidum. The motor activity induced by DAMGO was blocked by procaine microinjected into either the MD or the MEA. In contrast, procaine microinjected into the MD did not block motor activity elicited by AMPA while procaine into the MEA abolished the behavioral activation. These data indicate that the involvement of efferent projections from the ventral pallidum to either the MD or MEA in motor activation depends upon the type of receptor stimulated in the ventral pallidum.     

Effect of caries preventive measures on Streptococcus mutans and lactobacilli in selected mothers

Abstract – Mothers of first-born babies were selected on the basis of high salivary counts of Streptococcus mutans. All experimental subjects were given a basic caries preventive program in order to decrease the level of S. Mutans in saliva. the program included dietary counseling, which stressed the role of sucrose in the accumulation of S. Mutans. The treatment was carried out in a public dental office. The effect of the treatment was assessed by microbiological examination of salivary levels of S. mutars and lactobacilli. a stratistically significant reducation in both S. mutans and lactobacilli was found. The basic preventive program was effective in reducing the nuber of S. mutans below a selected threshold value of 3000000 CFU per mlsaliva in 60% of the mothers. In the remaining subjects chlorhexidine treatment was required to suppress the salivary levels of S. mutans below this value.     

Oxidative stress and matrix metalloproteinase-9 activity in the liver after hypoxia and reoxygenation with 21% or 100% oxygen in newborn piglets

We designed a randomized controlled study to identify and compare the liver tissue responses in systemic hypoxia and resuscitation with 21% and 100% oxygen using an animal model of neonatal hypoxia and reoxygenation. Twenty-seven piglets (1–3 days old, weight 1.5–2.0 kg) were acutely instrumented and mechanically ventilated. The animals underwent 2 h of normocapnic alveolar hypoxia (10–15% oxygen) then reoxygenation with 21% or 100% oxygen for 1 h, then 1 h with 21% oxygen. Controls were sham-operated without hypoxia-reoxygenation. After 2 h of reoxygenation liver tissue samples were immediately processed for histological and biochemical analyses of markers of oxidative stress and tissue injury. Two hours of hypoxia caused a significant reduction in mean arterial pressure with cardiogenic shock and metabolic acidemia, with similar recovery upon resuscitation with 21% and 100% oxygen. After 2 h of reoxygenation, the hepatic GSSG:total glutathione ratio and matrix metalloproteninase-9 activity, which correlated with the portal venous oxygenation at 15 min of reoxygenation, were greater in the 100% group and hepatic lactate level was higher in the 21% group than the controls (all P < 0.05). Both hypoxic-reoxygenated groups had similarly elevated hepatic Bcl-2 levels. Apart from more non-distinct mitochondria identified in the 100% group, hepatic tissue adenylate energy charge and plasma transaminases levels did not differ among groups. We concluded that in this acute model of neonatal hypoxia and reoxygenation, resuscitation using 21% oxygen avoids the excess oxidative stress and elevated matrix metalloproteninase-9 activity in the liver when 100% oxygen was used. The study supports the conservative use of oxygen in optimizing post-hypoxic hepatic recovery.     

Primary HIV-1 R5 isolates from end-stage disease display enhanced viral fitness in parallel with increased gp120 net charge

To better understand the evolution of the viral envelope glycoproteins (Env) in HIV-1 infected individuals who progress to AIDS maintaining an exclusive CCR5-using (R5) virus population, we cloned and sequenced the env gene of longitudinally obtained primary isolates. A shift in the electrostatic potential towards an increased net positive charge was revealed in gp120 of end-stage viruses. Residues with increased positive charge were primarily localized in the gp120 variable regions, with the exception of the V3 loop. Molecular modeling indicated that the modifications clustered on the gp120 surface. Furthermore, correlations between increased Env net charge and lowered CD4⁺ T cell counts, enhanced viral fitness, reduced sensitivity to entry inhibitors and augmented cell attachment were disclosed. In summary, this study suggests that R5 HIV-1 variants with increased gp120 net charge emerge in an opportunistic manner during severe immunodeficiency. Thus, we here propose a new mechanism by which HIV-1 may gain fitness.     

Sex differences in acute and long‐term brain recovery after concussion

Concussion is associated with acute disturbances in brain function and behavior, with potential long‐term effects on brain health. However, it is presently unclear whether there are sex differences in acute and long‐term brain recovery. In this study, magnetic resonance imaging (MRI) was used to scan 61 participants with sport‐related concussion (30 male, 31 female) longitudinally at acute injury, medical clearance to return to play (RTP), and 1‐year post‐RTP. A large cohort of 167 controls (80 male, 87 female) was also imaged. Each MRI session assessed cerebral blood flow (CBF), along with white matter fractional anisotropy (FA) and mean diffusivity (MD). For concussed athletes, the parameters were converted to difference scores relative to matched control subgroups, and partial least squares modeled the main and sex‐specific effects of concussion. Although male and female athletes did not differ in acute symptoms or time to RTP , all MRI measures showed significant sex differences during recovery. Males had greater reductions in occipital‐parietal CBF (mean difference and 95%CI: 9.97 ml/100 g/min, [4.84, 15.12] ml/100 g/min, z = 3.73) and increases in callosal MD (9.07 × 10⁻⁵, [−14.14, −3.60] × 10⁻⁵, z = −3.46), with greatest effects at 1‐year post‐RTP. In contrast, females had greater reductions in FA of the corona radiata (16.50 × 10⁻³, [−22.38, −11.08] × 10⁻³, z = −5.60), with greatest effects at RTP. These findings provide new insights into how the brain recovers after a concussion, showing sex differences in both the acute and chronic phases of injury.