Analysis of the genes coding for subunit 10 and 15 of cytochrome <Emphasis Type="Italic">c</Emphasis> oxidase in Alzheimer’s disease

Decay of mitochondria and oxidative stress are associated with normal aging, but many neurodegenerative diseases, and particularly Alzheimer’s disease (AD), are characterized by a significant increase in the intensity of these traits. Recent data suggest the possible contribution of heme deficiency to the progressive derangement of mitochondria in AD brain; shortage of heme, and particularly of heme-a, actually leads to loss of mitochondrial cytochrome c oxidase (COX), abnormal production of reactive oxygen species and altered amyloid precursor protein metabolism. We reasoned that differences in the amount and/or functioning of COX assembly subunit 10 (COX10) and 15 (COX15), the key enzymes involved in heme-a biosynthesis, could be linked to variations of the individual risk to develop AD. We analyzed their mRNA expression in the hippocampus from AD patients and controls, investigated the existence of nucleotide variations in their DNA sequences and analyzed their distribution in large groups of AD and control individuals. COX 15 mRNA was significantly more abundant in the cerebral tissue of AD patients (3.18 ± 1.70 vs. 1.22 ± 0.66 μg, normalized dose, P = 0.01). The IVS-178G>A SNP in COX10 and the c+1120C>T SNP in COX15 were significantly less represented in the patient group (P < 0.001 and P = 0.017, respectively) with respective odd ratios of 0.22 and 0.59, suggesting a possible protective role toward the risk for AD.     

Clinical validation of a novel enzyme‐linked immunosorbent spot assay‐based in vitro diagnostic assay to monitor cytomegalovirus‐specific cell‐mediated immunity in kidney transplant recipients: a multicenter,longitudinal, prospective,observational study

Impaired cytomegalovirus (CMV)‐specific cell‐mediated immunity (CMV‐CMI) is a major cause of CMV reactivation and associated complications in solid‐organ transplantation. Reliably assessing CMV‐CMI is desirable to individually adjust antiviral and immunosuppressive therapy. This study aimed to evaluate the suitability of T‐Track^® CMV, a novel IFN‐γ ELISpot assay based on the stimulation of peripheral blood mononuclear cells with pp65 and IE‐I CMV proteins, to monitor CMV‐CMI following kidney transplantation. A prospective longitudinal multicenter study was conducted in 86 intermediate‐risk renal transplant recipients. CMV‐CMI, CMV viral load, and clinical complications were monitored over 6 months post‐transplantation. Ninety‐five percent and 88–92% ELISpot assays were positive pre‐ and post‐transplantation, respectively. CMV‐specific response was reduced following immunosuppressive treatment and increased in patients with graft rejection, indicating the ability of the ELISpot assay to monitor patients' immunosuppressive state. Interestingly, median pp65‐specific response was ninefold higher in patients with self‐clearing viral load compared to antivirally treated patients prior to first viral load detection (P < 0.001), suggesting that reactivity to pp65 represents a potential immunocompetence marker. Altogether, T‐Track^® CMV is a highly sensitive IFN‐γ ELISpot assay, suitable for the immunomonitoring of CMV‐seropositive renal transplant recipients, and with a potential use for the risk assessment of CMV‐related clinical complications (ClinicalTrials.gov Identifier: NCT02083042).     

End-expiratory lung volumes and density distribution patterns during partial liquid ventilation in healthy and oleic acid-injured sheep: a computed tomography study

OBJECTIVE: To determine end-expiratory lung volumes (EELVs) and the distribution of gas and perflubron during low- and high-dose partial liquid ventilation (PLV) in healthy and oleic-acid-injured lungs. DESIGN: A prospective, randomized study. SETTING: A university medical school laboratory approved for animal research. SUBJECTS: Adult sheep. INTERVENTIONS: A total of 18 sheep were randomly divided into two groups (healthy and oleic acid lung injury) and received PLV with perflubron at incremental doses. MEASUREMENTS AND MAIN RESULTS: Animals were ventilated in a volume-control mode with a positive end-expiratory pressure of 5 cm H2O. Baseline computed tomographic scans of the entire lung were obtained during end-expiratory hold. Thereafter, the animals were randomized to undergo either PLV alone (healthy group) or after oleic acid lung injury was introduced (injury group). In both groups, PLV was induced by instilling 10 mL/kg perflubron into the endotracheal tube over 5 mins (low-dose PLV). At 60 mins after dosing, another set of computed tomographic scans during end-expiratory hold was obtained. Thereafter, another 20 mL/kg perflubron was instilled in both groups (cumulative dose, 30 mL/kg perflubron, high-dose PLV), and computed tomographic scanning was repeated 60 mins later. EELVs were calculated. To study density distribution patterns, the lungs were divided into nine segments, and the mean Hounsfield attenuation number was calculated for each segment. In healthy animals, low-dose PLV did not change EELV (47.5 +/- 8.1 mL/kg vs. 44.5 +/- 6.1 mL/kg at 10 mL/kg perflubron), whereas high-dose PLV significantly increased EELV (58.1 +/- 3.3 mL/kg, p <.01). Oleic acid lung injury significantly reduced EELV (53.9 +/- 7.5 mL/kg vs. 43.9 +/- 8.7 mL/kg, p <.01). Low-dose PLV reestablished baseline EELV (59.8 +/- 10.5 mL/kg), and high-dose PLV resulted in a significant increase in EELV (89.2 +/- 12 mL/kg, p =.003). PLV increased the mean Hounsfield attenuation number along the ventrodorsal axis in the three coronal blocks in a dose-dependent manner. In the oleic acid lung injury group, PLV produced a more homogeneous pattern of density distribution, with the highest Hounsfield attenuation numbers observed in the medial segments. CONCLUSION: High-dose PLV significantly increased EELV in both states, indicating lung distention. Healthy lungs were filled in a dose-dependent, gravity-governed fashion, showing steep craniocaudal and ventrodorsal gradients. In the oleic acid lung injury model studied, perflubron tended to accumulate on top of the most severely injured dorsal and diaphragmatic parts, rendering effective recruitment by liquid positive end-expiratory pressure in these regions questionable.     

In-vitro performance of a single-chambered total artificial heart in a Fontan circulation

Journal of Artificial Organs - An in-vitro study was conducted to investigate the general feasibility of using only one pumping chamber of the SynCardia total artificial heart (TAH) as a...     

Accuracy of portable quantitative capnometers and capnographs under prehospital conditions

This study was designed to assess the pCO(2) accuracy of portable mainstream (Tidal Wave, Novametrix; Propaq 106, Protocol) and sidestream capnometers (Capnocheck 8200, BCI; Capnocount mini, Weinmann; NPB-75, Nellcor Puritan Bennett; SC-210, Pryon) with respect to international standards and preclinical emergency conditions. Measurements were performed under temperature conditions of +22 degrees C and -20 degrees C using dry gas mixtures with different CO(2) concentrations (STPD) and in patients ventilated with pure oxygen (BTPS). Accuracy presented to be between +1% (Capnocheck) and +12% (Propaq) (STPD) and between -0.4% (Capnocheck) and +11% (Tidal Wave) (BTPS). The measurements were affected by low ambient temperature only in the NPB-75 (+15%). Our results indicate that portable quantitative capnometers are able to fulfill accuracy requirements as requested by international standards but can be affected by changing ambient temperatures.     

The link between childhood trauma and dissociation in frequent users of classic psychedelics and dissociatives

Background: Childhood trauma severity is associated with the level of subsequent substance use as well as with the self-reported severity of dissociation. Classic psychedelics and dissociatives target neurotransmitter systems thought to be involved in the onset of dissociative symptoms and may evoke severe and long-lasting symptoms of depersonalization in some users. However, it is currently unclear whether drug use puts people with a history of childhood trauma at higher risk of developing dissociative symptoms.

Objectives: The current study investigates whether the one-year prevalence of substance use significantly moderates the link between childhood trauma and the severity of depersonalization.

Methods: Participants (n = 297, of which 80.2% were active users) filled out an online self-report questionnaire including the Childhood Trauma Questionnaire (CTQ), the Cambridge Depersonalisation Scale (CDS), and information about their substance use.

Results: Results indicate that childhood trauma and substance use are significant individual predictors of dissociation scores in this sample, but no moderation of substance use on the link between childhood trauma and depersonalization was established.

Conclusions: It is hypothesized that the quality (particularly the context) of the experience of substance use rather than the sheer quantity may be responsible for the manifestation of depersonalization.