Clinical- and surgery-specific risk factors for post-operative sepsis: a systematic review and meta-analysis of over 30 million patients

Surgery Today - Post-operative sepsis is a severe complication of surgery, which often worsens the clinical outcomes. While several risk factors have been identified, the importance of others...     

Age-related differences in vastus lateralis fascicle behavior during fast accelerative leg-extension movements

Leg-extensor rate of power development (RPD) decreases during aging. This study aimed to identify the underlying mechanism of the age-related decline in RPD during a fast acceleration in terms of in vivo vastus lateralis (VL) fascicle shortening behavior. Thirty-nine men aged between 25 and 69 years performed three maximal isokinetic leg-extensor tests with a fixed initial acceleration of 45° knee extension in 150 ms until 340°/s knee angular velocity. RPD, VL activity, and ultrasound images were recorded to assess (relative) fascicle shortening and mean shortening velocity for the phases of electromechanical delay, pretension, and acceleration. Our findings show that fascicle shortening and mean shortening velocity during a fast action increase with aging (0.002 per year, P = .035 and 0.005 s⁻¹ per year, P = .097, respectively), mainly due to a higher amount of shortening in the phase of electromechanical delay. The ratio of VL fascicle length over upper leg length at rest showed a negative correlation (r = −.46, P = .004) with RPD/body mass, while pennation angle at rest showed a trend toward a positive correlation (r = .28, P = .089). To conclude, our findings indicate that the ability to reach high VL fascicle shortening velocities in vivo is not reduced in older men while performing preprogrammed fast accelerations. The greater amount of fascicle shortening in old age is probably the result of age-related differences in the tendinous properties of the muscle-tendon complex, forcing the fascicles to shorten more in order to transmit the muscle force to the segment.     

A chasing dead-end case report: a fatal lead intoxication following an attempted homicide

Forensic Toxicology - In developed countries, lead intoxication is decreasing in adults as sources of contamination were considerably reduced. Hence, cases of lead encephalopathy have become...     

Exploratory relationships between cognitive improvements and training induced plasticity in hippocampus and cingulum in a rat model of mild traumatic brain injury: a diffusion MRI study

Traumatic brain injury (TBI) is a major cause of long-term cognitive deficits, even in mild TBI patients. Computerized cognitive training can help alleviate complaints and improve daily life functioning of TBI patients. However, the underlying biological mechanisms of cognitive training in TBI are not fully understood. In the present study, we utilised for the first time a touchscreen cognitive training system in a rat model of mild TBI. Moreover, we wanted to examine whether the beneficial effects of a cognitive training are task-dependent and selective in their target. Specifically, we examined the effect of two training tasks, i.e. the Paired Associate Learning (PAL) task targeting spatial memory functioning and 5-Choice Continuous Performance (5-CCP) task loading on attention and inhibition control, on the microstructural organization of the hippocampus and cingulum, respectively, using diffusion tensor imaging (DTI). Our findings revealed that the two training protocols induced similar effects on the diffusion MRI metrics. Further, in the TBI groups who received training microstructural organization in the hippocampus and cingulum improved (as denoted by increases in fractional anisotropy), while a worsening (i.e., increases in mean diffusivity and radial diffusivity) was found in the TBI control group. In addition, these alterations in diffusion MRI metrics coincided with improved performance on the training tasks in the TBI groups who received training. Our findings show the potential of DTI metrics as reliable measure to evaluate cognitive training in TBI patients and to facilitate future research investigating further improvement of cognitive training targeting deficits in spatial memory and attention.

     

Role of VIP1/PACAP receptors in postoperative ileus in rats

1. Vasoactive intestinal polypeptide (VIP) is an inhibitory neurotransmitter in the enteric nervous system. We investigated the role of VIP₁/PACAP receptors in postoperative ileus in rats.
2. Different degrees of inhibition of the gastrointestinal transit, measured by the migration of Evans blue, were achieved by skin incision, laparotomy or laparotomy plus mechanical stimulation of the gut.
3. The transit after skin incision or laparotomy was not altered by the VIP₁/PACAP receptor antagonist Ac-Hisl,D-Phe², K¹⁵, R¹⁶, VIP(3–7), GRF(8–27)-NH₂ nor by the VIP₁/PACAP receptor agonist K¹⁵, R¹⁶, VIP(1–7), GRF(8–27)-NH₂ and the VIP₂/PACAP receptor agonist RO 25-1553 (5 μg kg⁻¹).
4. However, the transit after laparotomy plus mechanical stimulation was significantly enhanced by the VIP₁/PACAP receptor antagonist, whereas it was further inhibited by the VIP₁/PACAP receptor agonist. The combination of the VIP₁/PACAP receptor agonist and antagonist counteracted the effect of both drugs alone. The VIP₂/PACAP receptor agonist did not alter the effect of the VIP₁/PACAP receptor antagonist.
5. The combination of the VIP₁/PACAP receptor antagonist plus the nitric oxide (NO) synthase inhibitor L-nitroarginine had no effect on the transit after laparotomy plus mechanical stimulation, while the transit after skin incision was significantly decreased.
6. These findings suggest the involvement of VIP₁/PACAP receptors, next to NO, in the pathogenesis of postoperative ileus. However, the combination of the VIP₁/PACAP antagonist and the NO synthase inhibitor abolished the beneficial effect of each drug alone, suggesting the need for one of the inhibitory neurotransmitters to enable normal gastrointestinal transit.

     

Clinical validation of saquinavir/ritonavir genotypic resistance score in protease-inhibitor-experienced patients

OBJECTIVE: To identify a genotypic score for resistance to saquinavir boosted with ritonavir (SQV/r; 1,000/100 mg twice daily)-based regimens in protease inhibitor (PI)-experienced patients. METHODS: One-hundred and fifty-one PI-experienced patients receiving a SOV/r-containing regimen were enrolled retrospectively. The virological response (VR) was defined as the decrease in HIV RNA at months 3-5. The effect of each mutation in the protease gene on the VR to SQV/r regimen was assessed using non-parametric univariate analyses and then a step-by-step analysis was carried out using a Jonckheere-Tepstra (JT) nonparametric test to retain the group of mutations most strongly associated with VR. RESULTS: Among the 138 patients with detectable plasma SQV, the median VR was -1.48 [range: -4 to +1.2] log10 copies/ml. Changes at 12 codons were associated with a reduced VR to SQV/r: codons 10, 15, 20, 24, 46, 54, 62, 71, 73, 82, 84 and 90. The JT procedure led to selection of the following genotypic score, 10+15+20+ 24+62+73+82+84+90, as providing the strongest association with VR. In the 35 patients with none of the mutations in this score, the median decrease in HIV RNA was -2.24 log10 copies/ml and it was -1.88 (n=29), -1.43 (n=24), -0.52 (n=30), -0.18 (n=9), -0.11 (n=6) and -0.30 (n=5) log10 copies/ml in those with 1, 2, 3, 4, 5 and 6 mutations, respectively. CONCLUSION: With this resistance score to SQV/r, the isolates were classified as having no evidence of resistance (0-2), possible resistance (3) or resistance (> or =4) by grouping the number of mutations in samples for which the viral load reduction was similar.     

Allele variations in the OCA2 gene (pink-eyed-dilution locus) are associated with genetic susceptibility to melanoma

The occuloalbinism 2 (OCA2) gene, localized at 15q11, encodes a melanosomal transmembrane protein that is involved in the most common form of human occulo-cutaneous albinism, a human genetic disorder characterized by fair pigmentation and susceptibility to skin cancer. We wondered whether allele variations at this locus could influence susceptibility to malignant melanoma (MM). In all, 10 intragenic single-nucleotide polymorphisms (SNPs) were genotyped in 113 patients with melanomas and in 105 Caucasian control subjects with no personal or family history of skin cancer. By comparing allelic distribution between cases and controls, we show that MM and OCA2 are associated (p value=0.030 after correction for multiple testing). Then, a recently developed strategy, the 'combination test' enabled us to show that a combination formed by two SNPs was most strongly associated to MM, suggesting a possible interaction between intragenic SNPs. In addition, the role of OCA2 on MM risk was also detected using a logistic model taking into account the presence of variants of the melanocortin 1 receptor gene (MC1R, a key pigmentation gene) and all pigmentation characteristics as melanoma risk factors. Our data demonstrate that a second pigmentation gene, in addition to MC1R, is involved in genetic susceptibility to melanoma.     

Alu-mediated deletion of SOX10 regulatory elements in Waardenburg syndrome type 4

Waardenburg syndrome type 4 (WS4) is a rare neural crest disorder defined by the combination of Waardenburg syndrome (sensorineural hearing loss and pigmentation defects) and Hirschsprung disease (intestinal aganglionosis). Three genes are known to be involved in this syndrome, that is, EDN3 (endothelin-3), EDNRB (endothelin receptor type B), and SOX10. However, 15-35% of WS4 remains unexplained at the molecular level, suggesting that other genes could be involved and/or that mutations within known genes may have escaped previous screenings. Here, we searched for deletions within recently identified SOX10 regulatory sequences and describe the first characterization of a WS4 patient presenting with a large deletion encompassing three of these enhancers. Analysis of the breakpoint region suggests a complex rearrangement involving three Alu sequences that could be mediated by a FosTes/MMBIR replication mechanism. Taken together with recent reports, our results demonstrate that the disruption of highly conserved non-coding elements located within or at a long distance from the coding sequences of key genes can result in several neurocristopathies. This opens up new routes to the molecular dissection of neural crest disorders.     

HLA -A, -C, -B, -DRB1, -DQB1 and -DPB1 allele and haplotype frequencies in 4514 healthy Norwegians

We report HLA-A, -C, -B, -DRB1, -DQB1 and -DPB1 allele frequencies and estimated haplotype frequencies from 4514 healthy Norwegians who volunteered to participate in the Norwegian Bone Marrow Donor Registry. HLA genotyping was conducted on a Next Generation Sequencing platform. Data were analyzed using Arlequin and Pypop software. No significant deviations from Hardy-Weinberg Equilibrium were noted at any of the loci studied. We discuss the representability for the Norwegian population and argue that the presented HLA data could serve as a Norwegian reference panel.