Incisional hernia after upper abdominal surgery: A randomised controlled trial of midline versus transverse incision

Objectives: To determine whether a transverse incision is an alternative to a midline incision in terms of incisional hern

Low recurrence rate of a two-layered closure repair for primary and recurrent midline incisional hernia without mesh

Background: Incisional hernia is a serious complication after abdominal surgery and occurs in 11-23% of laparotomies. Repair can be done, for instance, with a direct suture technique, but recurrence rates are high. Recent literature advises the use of mesh repair. In contrast to this development, we studied the use of a direct suture repair in a separate layer technique. The objective of this retrospective observational study is to assess the outcomes (recurrences and complications) of a two-layered open closure repair for primary and recurrent midline incisional hernia without the use of mesh. Methods: In an observational retrospective cohort study, we analysed the hospital and outpatient records of 77 consecutive patients who underwent surgery for a primary or recurrent incisional hernia between 1st May 2002 and 8th November 2006. The repair consisted of separate continuous suturing of the anterior and posterior fascia, including the rectus muscle, after extensive intra-abdominal adhesiolysis. Results: Forty-one men (53.2%) and 36 women (46.8%) underwent surgery. Sixty-three operations (81.8%) were primary repairs and 14 (18.2%) were repairs for a recurrent incisional hernia. Of the 66 patients, on physical examination, three had a recurrence (4.5%) after an average follow-up of 2.6 years. The 30-day postoperative mortality was 1.1%. Wound infection was seen in five patients (6.5%). Conclusions: A two-layered suture repair for primary and recurrent incisional hernia repair without mesh with extensive adhesiolysis was associated with a recurrence rate comparable to mesh repair and had an acceptable complication rate

The Mechanisms of Codon Reassignments in Mitochondrial Genetic Codes

Many cases of non-standard genetic codes are known in mitochondrial genomes. We carry out analysis of phylogeny and codon usage of organisms for which the complete mitochondrial genome is available, and we determine the most likely mechanism for codon reassignment in each case. Reassignment events can be classified according to the gain-loss framework. The gain represents the appearance of a new tRNA for the reassigned codon or the change of an existing tRNA such that it gains the ability to pair with the codon. The loss represents the deletion of a tRNA or the change in a tRNA so that it no longer translates the codon. One possible mechanism is Codon Disappearance, where the codon disappears from the genome prior to the gain and loss events. In the alternative mechanisms the codon does not disappear. In the Unassigned Codon mechanism, the loss occurs first, whereas in the Ambiguous Intermediate mechanism, the gain occurs first. Codon usage analysis gives clear evidence of cases where the codon disappeared at the point of the reassignment and also cases where it did not disappear. Codon disappearance is the probable explanation for stop to sense reassignments and a small number of reassignments of sense codons. However, the majority of sense to sense reassignments cannot be explained by codon disappearance. In the latter cases, by analysis of the presence or absence of tRNAs in the genome and of the changes in tRNA sequences, it is sometimes possible to distinguish between the Unassigned Codon and Ambiguous Intermediate mechanisms. We emphasize that not all reassignments follow the same scenario and that it is necessary to consider the details of each case carefully.Comment: 53 pages (45 pages, including 4 figures + 8 pages of supplementary information). To appear in J.Mol.Evo

Vitamin D levels in children and adolescents with chronic tic disorders: a multicentre study.

This study investigated whether vitamin D is associated with the presence or severity of chronic tic disorders and their psychiatric comorbidities. This cross-sectional study compared serum 25-hydroxyvitamin D [25(OH)D] (ng/ml) levels among three groups: children and adolescents (3-16 years) with CTD (n = 327); first-degree relatives (3-10 years) of individuals with CTD who were assessed for a period of up to 7 years for possible onset of tics and developed tics within this period (n = 31); and first-degree relatives who did not develop tics and were ≥ 10 years old at their last assessment (n = 93). The relationship between 25(OH)D and the presence and severity of tics, as well as comorbid obsessive-compulsive disorder (OCD) and attention-deficit/hyperactivity disorder (ADHD), were analysed controlling for age, sex, season, centre, latitude, family relatedness, and comorbidities. When comparing the CTD cohort to the unaffected cohort, the observed result was contrary to the one expected: a 10 ng/ml increase in 25(OH)D was associated with higher odds of having CTD (OR 2.08, 95% CI 1.27-3.42, p < 0.01). There was no association between 25(OH)D and tic severity. However, a 10 ng/ml increase in 25(OH)D was associated with lower odds of having comorbid ADHD within the CTD cohort (OR 0.55, 95% CI 0.36-0.84, p = 0.01) and was inversely associated with ADHD symptom severity (β = - 2.52, 95% CI - 4.16-0.88, p < 0.01). In conclusion, lower vitamin D levels were not associated with a higher presence or severity of tics but were associated with the presence and severity of comorbid ADHD in children and adolescents with CTD

Extensive molecular tinkering in the evolution of the membrane attachment mode of the Rheb GTPase

Rheb is a conserved and widespread Ras-like GTPase involved in cell growth regulation mediated by the (m)TORC1 kinase complex and implicated in tumourigenesis in humans. Rheb function depends on its association with membranes via prenylated C-terminus, a mechanism shared with many other eukaryotic GTPases. Strikingly, our analysis of a phylogenetically rich sample of Rheb sequences revealed that in multiple lineages this canonical and ancestral membrane attachment mode has been variously altered. The modifications include: (1) accretion to the N-terminus of two different phosphatidylinositol 3-phosphate-binding domains, PX in Cryptista (the fusion being the first proposed synapomorphy of this clade), and FYVE in Euglenozoa and the related undescribed flagellate SRT308; (2) acquisition of lipidic modifications of the N-terminal region, namely myristoylation and/or S-palmitoylation in seven different protist lineages; (3) acquisition of S-palmitoylation in the hypervariable C-terminal region of Rheb in apusomonads, convergently to some other Ras family proteins; (4) replacement of the C-terminal prenylation motif with four transmembrane segments in a novel Rheb paralog in the SAR clade; (5) loss of an evident C-terminal membrane attachment mechanism in Tremellomycetes and some Rheb paralogs of Euglenozoa. Rheb evolution is thus surprisingly dynamic and presents a spectacular example of molecular tinkering

Brief Report: AIP Mutation in Pituitary Adenomas in the 18th Century and Today

From New England Journal of Medicine, Volume 364, issue 1, p.43-50. Copyright © (2011) Massachusetts Medical Society. Reprinted with permission.Gigantism results when a growth hormone–secreting pituitary adenoma is present before epiphyseal fusion. In 1909, when Harvey Cushing examined the skeleton of an Irish patient who lived from 1761 to 1783,1-3 he noted an enlarged pituitary fossa. We extracted DNA from the patient’s teeth and identified a germline mutation in the aryl hydrocarbon–interacting protein gene (AIP). Four contemporary Northern Irish families who presented with gigantism, acromegaly, or prolactinoma have the same mutation and haplotype associated with the mutated gene. Using coalescent theory, we infer that these persons share a common ancestor who lived about 57 to 66 generations earlier

Recoding of Translation in Turtle Mitochondrial Genomes: Programmed Frameshift Mutations and Evidence of a Modified Genetic Code

A +1 frameshift insertion has been documented in the mitochondrial gene nad3 in some birds and reptiles. By sequencing polyadenylated mRNA of the chicken (Gallus gallus), we have shown that the extra nucleotide is transcribed and is present in mature mRNA. Evidence from other animal mitochondrial genomes has led us to hypothesize that certain mitochondrial translation systems have the ability to tolerate frameshift insertions using programmed translational frameshifting. To investigate this, we sequenced the mitochondrial genome of the red-eared slider turtle (Trachemys scripta), where both the widespread nad3 frameshift insertion and a novel site in nad4l were found. Sequencing the region surrounding the insertion in nad3 in a number of other turtles and tortoises reveal general mitochondrial +1 programmed frameshift site features as well as the apparent redefinition of a stop codon in Parker’s snake-neck turtle (Chelodina parkeri), the first known example of this in vertebrate mitochondria

Nonlinear spectral image fusion

In this paper we demonstrate that the framework of nonlinear spectral decompositions based on total variation (TV) regularization is very well suited for image fusion as well as more general image manipulation tasks. The well-localized and edge-preserving spectral TV decomposition allows to select frequencies of a certain image to transfer particular features, such as wrinkles in a face, from one image to another. We illustrate the effectiveness of the proposed approach in several numerical experiments, including a comparison to the competing techniques of Poisson image editing, linear osmosis, wavelet fusion and Laplacian pyramid fusion. We conclude that the proposed spectral TV image decomposition framework is a valuable tool for semi- and fully-automatic image editing and fusion

Wnt5a induces ROR1 to complex with HS1 to enhance migration of chronic lymphocytic leukemia cells.

ROR1 (receptor tyrosine kinase-like orphan receptor 1) is a conserved, oncoembryonic surface antigen expressed in chronic lymphocytic leukemia (CLL). We found that ROR1 associates with hematopoietic-lineage-cell-specific protein 1 (HS1) in freshly isolated CLL cells or in CLL cells cultured with exogenous Wnt5a. Wnt5a also induced HS1 tyrosine phosphorylation, recruitment of ARHGEF1, activation of RhoA and enhanced chemokine-directed migration; such effects could be inhibited by cirmtuzumab, a humanized anti-ROR1 mAb. We generated truncated forms of ROR1 and found its extracellular cysteine-rich domain or kringle domain was necessary for Wnt5a-induced HS1 phosphorylation. Moreover, the cytoplamic, and more specifically the proline-rich domain (PRD), of ROR1 was required for it to associate with HS1 and allow for F-actin polymerization in response to Wnt5a. Accordingly, we introduced single amino acid substitutions of proline (P) to alanine (A) in the ROR1 PRD at positions 784, 808, 826, 841 or 850 in potential SH3-binding motifs. In contrast to wild-type ROR1, or other ROR1P→︀A mutants, ROR1P(841)A had impaired capacity to recruit HS1 and ARHGEF1 to ROR1 in response to Wnt5a. Moreover, Wnt5a could not induce cells expressing ROR1P(841)A to phosphorylate HS1 or activate ARHGEF1, and was unable to enhance CLL-cell motility. Collectively, these studies indicate HS1 plays an important role in ROR1-dependent Wnt5a-enhanced chemokine-directed leukemia-cell migration

CD49d Is the strongest flow cytometry–based predictor of overall survival in chronic lymphocytic leukemia

Purpose Although CD49d is an unfavorable prognostic marker in chronic lymphocytic leukemia (CLL), definitive validation evidence is lacking. A worldwide multicenter analysis was performed using published and unpublished CLL series to evaluate the impact of CD49d as an overall (OS) and treatment-free survival (TFS) predictor. Patients and Methods A training/validation strategy was chosen to find the optimal CD49d cutoff. The hazard ratio (HR) for death and treatment imposed by CD49d was estimated by pooled analysis of 2,972 CLLs; Cox analysis stratified by center and stage was used to adjust for confounding variables. The importance of CD49d over other flow cytometry–based prognosticators (eg, CD38, ZAP-70) was ranked by recursive partitioning. Results Patients with ≥ 30% of neoplastic cells expressing CD49d were considered CD49d+. Decrease in OS at 5 and 10 years among CD49d+ patients was 7% and 23% (decrease in TFS, 26% and 25%, respectively). Pooled HR of CD49d for OS was 2.5 (2.3 for TFS) in univariate analysis. This HR remained significant and of similar magnitude (HR, 2.0) in a Cox model adjusted for clinical and biologic prognosticators. Hierarchic trees including all patients or restricted to those with early-stage disease or those age ≤ 65 years always selected CD49d as the most important flow cytometry–based biomarker, with negligible additional prognostic information added by CD38 or ZAP-70. Consistently, by bivariate analysis, CD49d reliably identified patient subsets with poorer outcome independent of CD38 and ZAP-70. Conclusion In this analysis of approximately 3,000 patients, CD49d emerged as the strongest flow cytometry–based predictor of OS and TFS in CLL