Decoding immune-related gene-signatures in colorectal neoplasia.

Background: Colorectal cancer (CRC) is a significant health issue, with notable incidence rates in Norway. The immune response plays a dual role in CRC, offering both protective effects and promoting tumor growth. This research aims to provide a detailed screening of immune-related genes and identify specific genes in CRC and adenomatous polyps within the Norwegian population, potentially serving as detection biomarkers. Methods: The study involved 69 patients (228 biopsies) undergoing colonoscopy, divided into CRC, adenomatous polyps, and control groups. We examined the expression of 579 immune genes through nCounter analysis emphasizing differential expression in tumor versus adjacent non-tumorous tissue and performed quantitative reverse transcription polymerase chain reaction (RT-qPCR) across patient categories. Results: Key findings include the elevated expression of CXCL1, CXCL2, IL1B, IL6, CXCL8 (IL8), PTGS2, and SPP1 in CRC tissues. Additionally, CXCL1, CXCL2, IL6, CXCL8, and PTGS2 showed significant expression changes in adenomatous polyps, suggesting their early involvement in carcinogenesis. Conclusions: This study uncovers a distinctive immunological signature in colorectal neoplasia among Norwegians, highlighting CXCL1, CXCL2, IL1B, IL6, CXCL8, PTGS2, and SPP1 as potential CRC biomarkers. These findings warrant further research to confirm their role and explore their utility in non-invasive screening strategies.

Is Corporate Social Responsibility investing a free lunch? The relationship between ESG, tail risk, and upside potential of stocks before and during the COVID-19 crisis.

Did Corporate Social Responsibility investing benefit shareholders during the COVID-19 pandemic crisis? Distinguishing between downside tail risk and upside reward potential of stock returns, we provide evidence from 5,073 stocks listed on stock markets in ten countries. The findings suggest that better ESG ratings are associated with lower downside risk, but also with lower upside return potential. Thus, ESG ratings helped investors to reduce their risk exposure to the market turmoil caused by the pandemic, while maintaining the fundamental trade-off between risk and reward.

Meat tastes good, legumes are healthy and meat substitutes are still strange - The practice of protein consumption among Swedish consumers.

Replacing some meat with grain legumes would benefit human health, the environment and agriculture. This study analysed legume and meat consumption practices by investigating consumer perceptions and competences relating to lightly processed grain legumes (LPL), legume-based meat substitutes (LBMS) and meat in Sweden, and how these (and demographic variables) influenced stated intention to change consumption. Major differences in consumer perceptions of LPL and LBMS compared with meat related to product attractiveness and status, with meat seen as more fun, popular, suitable in diets and for festive occasions, and tastier. Most consumers knew of the environmental impact of meat and health benefits of LPL. Country of origin, i.e. Swedish origin, was important for many consumers (especially for meat and women). Preferences relating to health and environmental impact were important for intention to decrease meat consumption. Perceived environmental impact was important for intention to change consumption of LPL, but taste, healthiness, weight control, ease of preparation and suitability in the diet were equally or more important. Leveraging stated consumer willingness and intention to eat more LPL by making LPL more accessible to consumers could increase their consumption. For LBMS, there are still important barriers in terms of taste, familiarity and overall attractiveness of these products that need to be overcome to increase their consumption in Sweden.

The cutting edge-an investigation into the pressure necessary for cutting skin with different knife blade types.

Sharp force trauma is routinely encountered in forensic practice. Often the question is posed, how much pressure or energy would have been necessary to inflict a cut with a specific knife, in order to further characterize the perpetrator or determine his intent to cause harm. This paper investigates two knife blades and its individual pressures needed to cut through the epidermis and dermis. In order to examine the necessary force for cutting through the skin, we performed experiments on a piglet skin-on-gelatin phantom. Two similarly small knives-a paring knife with a serrated blade and a Swiss Army pocket knife with a smooth blade-were moved over the phantom surface using a mobile cutting apparatus with varying weight on the load arm with the knife. The depth of the cut was to be determined according to a scale from zero to three: grade 0 = no cut; grade 1 = cut into epidermis only; grade 2 = cut into dermis; grade 3 = complete transection of the entire skin. Each cut inflicted at a specific pressure force was assessed closely in order to ascertain depth, calculate the velocity, and ultimately determine the point at which a cut would inflict grade 3 damage. The smooth blade of a pocket knife needed at least 1900g pressure in order to slice through pig skin mounted on a thick gelatin block, whereas a serrated blade of a paring knife managed to cut into or through the dermis at a comparatively lower force of 700g. Our study shows that at the same cutting velocity, a significant difference in pressure is necessary to inflict the same degree of damage.

Usefulness of Genetic Testing in Sudden Cardiac Arrest Survivors With or Without Previous Clinical Evidence of Heart Disease.

Genetic testing in survivors of sudden cardiac arrest (SCA) with a suspicious cardiac phenotype is considered clinically useful, whereas its value in the absence of phenotype is disputed. We aimed to evaluate the clinical utility of genetic testing in survivors of SCA with or without cardiac phenotype. Sixty unrelated SCA survivors (median age: 34 [interquartile range 20 to 43] years, 82% male) without coronary artery disease were included: 24 (40%) with detectable cardiac phenotype (Ph(+)SCA) after the SCA event and 36 (60%) with no clear cardiac phenotype (Ph(-)SCA). The targeted exome sequencing was performed using the TruSight-One Sequencing Panel (Illumina). Variants in 185 clinically relevant cardiac genes with minor allele frequency <1% were analyzed. A total of 32 pathogenic or likely pathogenic variants were found in 27 (45%) patients: 17 (71%) in the Ph(+)SCA group and 10 (28%) in the Ph(-)SCA group. Sixteen (67%) Ph(+)SCA patients hosted mutations congruent with the suspected phenotype, in which 12 (50%) were cardiomyopathies and 4 (17%) channelopathies. In Ph(-)SCA cases, 6 (17%) carried a mutation in cardiac ion channel genes that could explain the event. The additional 4 (11%) mutations in this group, could not explain the phenotype and require additional studies. In conclusion, cardiac genetic testing was positive in nearly 2/3 patients of the Ph(+)SCA group and in 1/6 of the Ph(-)SCA group. The test was useful in both groups to identify or confirm an inherited heart disease, with an important impact on the patient care and first-degree relatives at risk.

Penetration Depths of Conducted Electrical Weapon Probes Into Human Skull Phantoms.

Occasional case reports have described isolated cases of conducted electrical weapon (CEW) probes piercing the human skull. In an experimental setting, we examined whether these cases were just unfortunate incidents, how deeply such probes can pierce the skull, and whether firing distance and CEW probe type play a role in the skull-piercing capability.We fired 5 different CEW cartridges (XP 10.6 m, XP 7.6 m, smart 10.6 m, smart 7.6 m, and smart probe 7.6 m) from 4 different distances (0.5, 1, 2, and 4 m) at head phantoms made of either 5- or 7-mm-thick polyurethane spheres covered with a thin layer of gelatine and buckskin. The piercing depths were recorded by computed tomographic scanning.All tested cartridges managed to pierce the head phantoms. Piercing depths of up to 6.6 mm in the 5-mm heads and depths of almost 5 mm in the 7-mm heads were recorded. Deepest piercing depths were attained with firing distances of 2 m or less.Our results showed that all tested CEW probes are capable of piercing the skull and that shorter firing distances tend to lead to deeper piercing depths.

High Production of Neuraminidase by a Vibrio cholerae Non-O1 Strain--the First Possible Alternative to Toxigenic Producers.

Vibrio cholerae neuraminidase (VCNA) is widely used in biochemical and medical research, in processes for preparing homogenous sialoconjugates, and in the pharmaceutical industry. Its production by non-toxigenic strains is quite desirable, in order to avoid the expensive safety measures. Here, we report the first method for highly effective production of a novel, purified V. cholerae extracellular neuraminidase from a non-toxigenic strain. The enzyme is highly active, and its properties, as well as the responsible gene nanH, are practically identical with those of the toxigenic strains. It cleaves α,2 → 3 and α,2 → 6 glycosidic bonds with highest affinity (K M 1.7 × 10(-5) µM) for human transferrin. The deduced amino acid sequence of the enzyme reveals three binding sites for Ca(2+) and one for sialic acid. The sequence analysis of the nanH gene, being the first for a V. cholerae non-O1 strain, shows 99% identity with a new nanH allele of an O1 Vibrio strain. The simple laboratory technology for efficient production of the new VCNA is based on the use of common and cheap nutrient media and easily available inducer--glycomacropeptide. The rapid purification consists of salting-out and diethylaminoethanol (DEAE) and Q-Sepharose chromatography steps. Purified preparation contains no aldolase and protease, which gives the production scheme a great potential for industrial application.

Anastomotic leakage after laparoscopic single-port sigmoid resection: combined transanal and transabdominal minimal invasive management.

BACKGROUND: Laparoscopic colorectal surgery has become the gold standard in the therapy of benignant and malignant colorectal pathologies. Anastomotic leakage is still a reason for laparotomy; applying a diverting stoma or performing a Hartman's procedure is common [1, 2]. Laparoscopic treatment of an early-detected anastomotic leakage is suggested from other authors [3, 4]. In our video we demonstrate a combined minimal invasive transabdominal and transanal treatment concept in patients with early-detected anastomotic leakage. METHODS: Two consecutive patients developing an anastomotic leakage after single-port laparoscopic sigmoid resection for stage II/III diverticulitis (Hanson & Stock) were treated with a combined minimal invasive approach. Anastomotic leakage was diagnosed by triple contrast computed tomography on postoperative day 4 in patient one and on postoperative day 7 in patient two. Operative treatment was performed immediately on the same day without delay. RESULTS: In both patients a combined transanal and transabdominal approach was performed. First step was a diagnostic laparoscopy in order to exclude fecal peritonitis. Using a single-port device (SILS Port Covidien), transanal inspection of the anastomosis was also performed: In both patients anastomotic tissue margins were vital, and the leakage affected only a quarter of the anastomotic circumference. Transanal stitches were placed to close the anastomotic leakage. Laparoscopic transabdominal irrigation was performed, and two suction drainages were placed in the pelvis. Postoperative antibiotic treatment and a gradual return to slid food were carried out. Functional result at follow-up of 102 and 112 days (with rectoscopy) showed no residual leak and no stricture of the anastomosis, and both of patients had a normal rectal function.

[Atrial fibrillation-pharmacological therapy for rate and rhythm control]. / Vorhofflimmern - Medikamentöse Therapie bei Rhythmus- oder Frequenzkontrolle.

The therapeutic management of patients with atrial fibrillation is based on the three pillars (1) prevention of thromboembolism, (2) rate control, and (3) rhythm control. Patients with one or more risk factors should be treated with an oral anticoagulants in order to prevent stroke and to reduce mortality. The goals of rate control, prevention of heart failure and alleviation of atrial fibrillation related symptoms, normally can be achieved by pharmacological agents slowing the conduction in the AV node (e. g. ß-blockers, calcium channel blockers, digoxin). For patients remaining symptomatic despite sufficient rate control adding a rhythm control strategy may be considered. The currently available antiarrhythmic drugs (e. g. flecainide, propafenone, sotalol, dronedarone, amiodarone) are characterized by a rather low efficacy in maintaining sinus rhythm and various possibly life threatening side effects. Therefore, invasive therapies as catheter ablation are frequently needed to achieve rhythm control in symptomatic patients with atrial fibrillation.

Molecular basis for fungicidal action of neothyonidioside, a triterpene glycoside from the sea cucumber, Australostichopus mollis.

Neothyonidioside is a triterpene glycoside (TG) isolated from the sea cucumber, Australostichopus mollis, that is potently cytotoxic to S. cerevisiae, but does not permeabilize cellular membranes. We mutagenized S. cerevisiae and isolated a neothionidioside-resistant (neo(R)) strain. Using synthetic genetic array mapping and sequencing, we identified NCP1 as the resistance locus. Quantitative HPLC revealed that neo(R)/ncp1 mutants have reduced ergosterol content. Ergosterol added to growth media reversed toxicity, demonstrating that neothionidioside binds directly to ergosterol, similar to the polyene natamycin. Ergosterol synthesis inhibitors ketoconazole and atorvastatin conferred resistance to neothionidioside in a dose-dependent manner showing that a threshold ergosterol concentration is required for toxicity. A genome-wide screen of deletion mutants against neothionidioside revealed hypersensitivity of many of the component genes in the ESCRT complexes relating to multivesicular body formation. Confocal microscopy of cells stained with a vital dye showed blockage at this step. Thus, we propose neothionidioside may affect membrane curvature and fusion capability in the endosome-vacuole pathway.

The importance of class-I antiarrhythmic drug test in the evaluation of patients with syncope: unmasking Brugada syndrome.

INTRODUCTION: The Brugada syndrome (BrS) can first present with syncope. Class-I antiarrhythmic drug (AAD) test is used to unmask the diagnostic coved-type ECG pattern in case it is not spontaneously present. The aim of the study was to analyze patients with BrS presenting with syncope as first manifestation and compare patients with syncope and a spontaneous coved-type ECG to patients with syncope in whom a class-I AAD test unmasked the disease. METHODS AND RESULTS: Fifty-eight of 157 probands (36.9%) had syncope as first manifestation of the disease. Twenty-six patients (44.8%, group A) showed a spontaneous coved-type ECG diagnostic for BrS at first presentation. In 32 patients (55.2%, group B) without spontaneous coved-type ECG pattern at first presentation (36% normal ECGs and 19% type-II ECG pattern), a class-I AAD test unmasked the disease. Twenty-one patients of group A and 29 patients of group B underwent implantable cardioverter defibrillator (ICD) implantation. The mean follow up as 9.7 ± 55.7 month. Four patients in group A (15.4%) and 3 patients (9.3%) in group B had appropriate ICD shock delivery due to ventricular fibrillation or ventricular tachycardia (P = NS). CONCLUSION: One of 3 patients with BrS presents first with syncope. More than one-third of these patients have a normal ECG at investigation for syncope and the correct diagnosis would have been missed without a class-I AAD test. Patients presenting with syncope are at similar risk irrespective of the presence of a spontaneous coved-type ECG.

Added value of transoesophageal echocardiography during transseptal puncture performed by inexperienced operators.

AIMS: Transseptal puncture (TP) appears to be safe in experienced hands; however, it can be associated with life-threatening complications. The aim of our study was to demonstrate the added value of routine use of transoesophageal echocardiography (TEE) for the correct positioning of the transseptal system in the fossa ovalis, thus potentially preventing complications during fluoroscopy-guided TP performed by inexperienced operators. METHODS AND RESULTS: Two hundred and five patients undergoing pulmonary vein isolation procedure (PVI) for drug-resistant paroxysmal or persistent atrial fibrillation were prospectively included. When the operator (initially blinded to TEE) assumed that the transseptal system was in a correct position according to fluoroscopical landmarks, the latter was then checked with TEE unblinding the physician. If necessary, further refinement of the catheter position was performed. Refinement >10 mm, or in case of catheter pointing directly at the aortic root or posterior wall were considered as major repositioning. Thirty-four patients required major repositioning. Regression analysis revealed age (P: 0.0001, Wald: 12.9, 95% confidence interval: 1.04-1.16), left atrial diameter (P: 0.01, Wald: 6.6, 95% confidence interval: 1.04-1.34), previous PVI (P: 0.01, Wald: 6.3, 95% confidence interval: 1.31-8.76), and atrial septal thickness (P: 0.03, Wald: 4.5, 95% confidence interval: 1.05-3.4) as independent predictors of major revision with TEE. CONCLUSION: Routine 2D TEE in addition to traditional fluoroscopic TP appears to be very useful to guide the TP assembly in a correct puncture position and thus, to avoid TP-related complications. However, further randomized prospective comparative studies are necessary to support these suggestions.

Does the cerebral state index separate consciousness from unconsciousness?

BACKGROUND: The Cerebral State Monitor™ (CSM) is an electroencephalogram (EEG)-based monitor that is claimed to measure the depth of hypnosis during general anesthesia. We calculated the prediction probability (P(K)) for its ability to separate consciousness from unconsciousness in surgical patients with different anesthetic regimens. METHODS: Digitized EEG recordings of a previous study of 40 nonpremedicated, adult patients undergoing elective surgery under general anesthesia were replayed using an EEG player and reanalyzed using the CSM. Patients were randomly assigned to receive either sevoflurane-remifentanil or propofol-remifentanil. The study design included a slow induction of anesthesia and an episode of intended wakefulness. CSM values at loss and return of consciousness were compared. P(K) was calculated from values 30 seconds before and 30 seconds after loss and return of consciousness. RESULTS: The P(K) for the differentiation between consciousness and unconsciousness was 0.75 ± 0.03 (mean ± SE). For sevoflurane-remifentanil, P(K) was 0.71 ± 0.04. For propofol-remifentanil, P(K) was 0.81 ± 0.03. CONCLUSIONS: The ability of CSM for separation of consciousness and unconsciousness was comparable to other commercially available EEG-based indices.

Correlation of fat embolism severity and subcutaneous fatty tissue crushing and bone fractures.

Pulmonary fat embolism (PFE) is frequently encountered in blunt trauma. The clinical manifestation ranges from no impairment in light cases to death due to right-sided heart failure or hypoxaemia in severe cases. Occasionally, pulmonary fat embolism can give rise to a fat embolism syndrome (FES), which is marked by multiorgan failure, respiratory disorders, petechiae and often death. It is well known that fractures of long bones can lead to PFE. Several authors have argued that PFE can arise due to mere soft tissue injury in the absence of fractures, a claim other authors disagree upon. In this study, we retrospectively examined 50 victims of blunt trauma with regard to grade and extent of fractures and crushing of subcutaneous fatty tissue and presence and severity of PFE. Our results indicate that PFE can arise due to mere crushing of subcutaneous fat and that the fracture grade correlated well with PFE severity (p = 0.011). The correlation between PFE and the fracture severity (body regions affected by fractures and fracture grade) showed a lesser significant correlation (p = 0.170). The survival time (p = 0.567), the amount of body regions affected by fat crushing (p = 0.336) and the fat crush grade (p = 0.485) did not correlate with the PFE grade, nor did the amount of body regions affected by fractures. These results may have clinical implications for the assessment of a possible FES development, as, if the risk of a PFE is known, preventive steps can be taken.

Comprehensive sensomics analysis of hop-derived bitter compounds during storage of beer.

For the first time, quantitative LC-MS/MS profiling of 56 hop-derived sensometabolites contributing to the bitter taste of beer revealed a comprehensive insight into the transformation of individual bitter compounds during storage of beer. The proton-catalyzed cyclization of trans-iso-α-acids was identified to be the quantitatively predominant reaction leading to lingering, harsh bitter tasting tri- and tetracyclic compounds such as, e.g. the cocongeners tricyclocohumol, tricyclocohumene, isotricyclocohumene, tetracyclocohumol, and epitetracyclocohumol, accumulating in beer during storage with increasing time and temperature. The key role of these transformation products in storage-induced trans-iso-α-acid degradation was verified for the first time by multivariate statistics and hierarchical cluster analysis of the sensomics data obtained for a series of commercial beer samples stored under controlled conditions. The present study offers the scientific basis for a knowledge-based extension of the shelf life of the desirable beer's bitter taste and the delay of the onset of the less preferred harsh bitter aftertaste by controlling the initial pH value of the beer and by keeping the temperature as low as possible during storage of the final beverage.

Dissociation between anterograde and retrograde conduction during transvenous cryoablation of parahissian accessory pathways.

Ablation of parahissian accessory pathways (APs) is a challenging procedure because of the high risk to provoke "iatrogenic" atrioventricular (AV) nodal block. The feasibility and safety of cryoablation (CA) have been already demonstrated both in patients with AV nodal reentry tachycardia and in those with anteroseptal APs. However, dissociation between anterograde and retrograde conduction after CA has not yet been described. We report two cases of CA of parahissian AP associated with transient dissociation between anterograde and retrograde conduction.

Pulmonary vein ostium shape and orientation as possible predictors of occlusion in patients with drug-refractory paroxysmal atrial fibrillation undergoing cryoballoon ablation.

AIMS: No specific data are available on the influence of pulmonary vein (PV) anatomy and shape on cryoballoon ablation (CA) catheter efficacy in delivering cryothermal energy and, consequently, in obtaining PV isolation. METHODS AND RESULTS: Among a larger series of patients (68) with drug-refractory paroxysmal atrial fibrillation who underwent CA in our department, 52 patients were included in our study. All of them had a multislice cardiac computed tomography (MSCT) before the procedure. We retrospectively evaluated their MSCT scans focusing our attention on PV ovality and orientation in the frontal plane. A fair inverse association was documented between the ovality index of the left PVs and the degree of occlusion (r=-0.486 and P<0.003 for the LSPV and r=-0.360 and P=0.033 for the LIPV), whereas no association was found between the ovality index of the right PVs and the degree of occlusion (r=-0.283 and P=0.083 for the RSPV and r=0.235 and P=0.093 for RIPV). Nevertheless, a strong inverse association was found between the orientation of the PV ostia and the degree of occlusion in each vein (r=-0.804 and P<0.001 for the LSPV, r=-0.415 and P=0.013 for LIPV, r=-0.798 and P<0.001 for the RSPV, and r=-0.867 and P<0.001 for RIPV). CONCLUSION: Pulmonary vein ostium shape and orientation evaluated by MSCT proved to be useful in predicting the degree of occlusion obtained during CA.

Anatomical extent of pulmonary vein isolation after cryoballoon ablation for atrial fibrillation: comparison between the 23 and 28 mm balloons.

BACKGROUND: Pulmonary vein isolation seems to occur in the distal part of the ostium leaving the atrium largely unablated when using the 23 mm cryoballoon catheter ablation for atrial fibrillation. We hypothesize that ablating with the larger 28 mm cryoballoon would target a wider portion of the left atrial cavity. AIM: To compare the anatomical extent of pulmonary vein isolation using electroanatomical mapping when performing atrial fibrillation ablation with a 23 mm or a 28 mm cryoballoon. METHODS: Eight consecutive patients selected for circumferential pulmonary vein cryoballoon isolation for highly symptomatic paroxysmal atrial fibrillation were randomly assigned to ablation with the 23 or 28 mm balloon. After ablation, electroanatomical mapping was performed to compare the anatomical extent of pulmonary vein isolation between the two balloon dimensions. RESULTS: Extent of pulmonary vein isolation significantly differed when the lesions with either balloon dimensions were compared. Pulmonary vein isolation only occurred in the tubular part of the ostium when performed with the 23 mm balloon. Conversely, the lesion created with the 28 mm balloon included a larger portion of the left atrium. In fact, when using the smaller balloon (23 mm) the mean documented extent of electrical isolation was 20.7 ± 2.8% of the maps' surface, whereas it was 40.2 ± 3.9% when performing ablation with the bigger balloon (28 mm). The difference in calculated area of electrical isolation between group A and B was statistically significant (P < 0.05). CONCLUSION: Pulmonary vein isolation occurs significantly more proximally in the atrium when performing atrial fibrillation ablation with a 28 mm cryoballoon when compared with a 23 mm balloon.

Accelerated idioventricular rhythm during ajmaline test: a case report.

We present an unusual transient pro-arrhythmic effect of ajmaline in a patient with resuscitated cardiac arrest and a left ventricular apical aneurysm. We discuss the clinical presentation and the possible physio-pathological explanation for this new pro-arrhythmic effect linked to administration of intravenous ajmaline.