Rectal perforation after laser hemorrhoidoplasty: a case report.

This case report outlines the intricate management of rectal perforation following laser hemorrhoidoplasty in a 31-year-old female, leading to an acute abdomen, sepsis, and multiorgan failure. Urgent laparoscopic exploration and the establishment of a double-loop colostomy were undertaken, marking the beginning of a complex course characterized by relapsed pelvic sepsis. Laser hemorrhoidoplasty has gained widespread acceptance for its minimally invasive approach in treating hemorrhoids. Remarkably, to our knowledge, the case we present is the first major complication reported after laser hemorrhoidoplasty, likely attributed to collateral thermic and mechanical tissue damage.

The UFM1 Pathway Impacts HCMV US2-Mediated Degradation of HLA Class I.

To prevent accumulation of misfolded proteins in the endoplasmic reticulum, chaperones perform quality control on newly translated proteins and redirect misfolded proteins to the cytosol for degradation by the ubiquitin-proteasome system. This pathway is called ER-associated protein degradation (ERAD). The human cytomegalovirus protein US2 induces accelerated ERAD of HLA class I molecules to prevent immune recognition of infected cells by CD8+ T cells. Using US2-mediated HLA-I degradation as a model for ERAD, we performed a genome-wide CRISPR/Cas9 library screen to identify novel cellular factors associated with ERAD. Besides the identification of known players such as TRC8, p97, and UBE2G2, the ubiquitin-fold modifier1 (UFM1) pathway was found to affect degradation of HLA-I. UFMylation is a post-translational modification resembling ubiquitination. Whereas we observe ubiquitination of HLA-I, no UFMylation was detected on HLA-I or several other proteins involved in degradation of HLA-I, suggesting that the UFM1 pathway impacts ERAD in a different manner than ubiquitin. Interference with the UFM1 pathway seems to specifically inhibit the ER-to-cytosol dislocation of HLA-I. In the absence of detectable UFMylation of HLA-I, UFM1 may contribute to US2-mediated HLA-I degradation by misdirecting protein sorting indirectly. Mass spectrometry analysis of US2-expressing cells showed that ribosomal proteins are a major class of proteins undergoing extensive UFMylation; the role of these changes in protein degradation may be indirect and remains to be established.

Correction to: A Genetic Investigation of the Well-Being Spectrum.

In the original version of this article, unfortunately, in the acknowledgement section "National Institutes of Health (NIH, R37 AG033590-08) to J Cacioppo" was omitted. This has been corrected by publishing this erratum.

A Genetic Investigation of the Well-Being Spectrum.

The interrelations among well-being, neuroticism, and depression can be captured in a so-called well-being spectrum (3-phenotype well-being spectrum, 3-WBS). Several other human traits are likely linked to the 3-WBS. In the present study, we investigate how the 3-WBS can be expanded. First, we constructed polygenic risk scores for the 3-WBS and used this score to predict a series of traits that have been associated with well-being in the literature. We included information on loneliness, big five personality traits, self-rated health, and flourishing. The 3-WBS polygenic score predicted all the original 3-WBS traits and additionally loneliness, self-rated health, and extraversion (R2 between 0.62% and 1.58%). Next, using LD score regression, we calculated genetic correlations between the 3-WBS and the traits of interest. From all candidate traits, loneliness and self-rated health were found to have the strongest genetic correlations (rg = - 0.79, and rg= 0.64, respectively) with the 3-WBS. Lastly, we use Genomic SEM to investigate the factor structure of the proposed spectrum. The best model fit was obtained for a two-factor model including the 5-WBS traits, with two highly correlated factors representing the negative- and positive end of the spectrum. Based on these analyses we propose to include loneliness and self-rated health in the WBS and use a 5-phenotype well-being spectrum in future studies to gain more insight into the determinants of human well-being.

Technical and Clinical Success and Long-Term Durability of Endovascular Treatment for Atherosclerotic Aortic Arch Branch Origin Obstruction: Evaluation of 144 Procedures.

OBJECTIVES: Endovascular treatment of atherosclerotic obstruction of aortic arch branch origins (AABO) has largely replaced open surgery, but long-term outcome data are lacking. This study evaluated mid-term and long-term results of these procedures. DESIGN: Retrospective cohort study. MATERIALS AND METHODS: Patients underwent endovascular treatment for symptomatic atherosclerotic stenosis of AABO between 1995 and 2012. Technical success was defined as uncomplicated revascularization and residual stenosis ≤30%. The primary end point was freedom from restenosis ≥50% on Duplex ultrasonography or magnetic resonance angiography. Secondary end points were freedom from target lesion revascularization or recurrent symptoms. RESULTS: 144 lesions were treated in 114 patients (75 female; mean age 66.3 years), by percutaneous transluminal angioplasty (PTA) in 20 patients and PTA and stent in 117 patients (brachiocephalic artery [BCA] 9/54; left common carotid artery [LCCA] 0/7; left subclavian artery [LSA] 11/56). The lesion could not be passed in four patients, and in three patients the intervention was terminated before angioplasty. The 30-day technical success was 94.4%, without deaths or strokes. Mean follow-up was 52.0 months (range 2-163 months). Restenosis-free survival was 95.6%, 92.9%, 87.6%, and 83.2% at 12, 24, 48, and 60 months, respectively. Log-rank test showed no significant difference between PTA only and PTA with additional stent placement at any point (p = .375), nor between BCA (n = 51), LCCA (n = 6), or LSA (n = 57). During follow-up, 27 patients (23.7%) became symptomatic (15 BCA, 1 LCCA, and 11 LSA); 19 patients with a restenosis of the target lesion (mean 56.7 months). Symptom-free survival was 94.7%, 92.0%, 82.3%, and 77.9% at 12, 24, 48, and 60 months, respectively. CONCLUSION: Endovascular treatment of aortic arch branch origin obstruction is safe and efficacious in experienced hands and can be considered as the preferred treatment, with good mid-term durability. Recurrent symptomatic lesions can be treated safely by renewed endovascular means.