Notes

Mechanochemical Rearrangements.
Even though its development starts early in utero, neonatal skin is still immature at birth relative to adult and undergoes a maturation process extending to the first years of life. It is now established that the stratum corneum is thinner and dryer and that skin contains less natural moisturizing factors and lipids in newborns compared to children and adults. Moreover, it has been shown that skin surface area expansion is not linear throughout life and is peaking perinatally, suggesting that baby skin has a higher epidermal cellular turnover. Despite growing resources showing differences between adult and infant skin physiology, molecular and metabolic specificities of baby skin are still poorly understood. To address this critical knowledge gap, we performed an integrative transcriptomic and metabolomic study comparing human primary foreskin and abdominal keratinocytes from male babies and female adults, respectively. Based on state-of-the-art integrative frameworks, our analyses revealed a major shift in the global energetic metabolism in baby foreskin keratinocytes compared to adult abdominal keratinocytes, highlighting increased amino acid metabolism and mitochondrial oxidative phosphorylation in baby cells to fuel the citric acid cycle, while showing glycolysis as the major cell energy source in adult cells.Laminin-332 pemphigoid is a rare and chronic autoimmune blistering disease which results in subepidermal blisters and erosive lesions predominantly localized to mucous membranes. As histologic inflammation is variable and non-complement-fixing IgG antibodies against laminin-332 are the predominant class of autoantibodies deposited at the epidermal basement membrane zone, we hypothesized that complement-independent pro-inflammatory and blistering pathways existed similarly to that previously shown in bullous pemphigoid. As autoantibodies to laminin α3 are most prevalent, we studied the major cellular response to blockade of laminin α3 using a well-characterized monoclonal antibody (P3H9-2). RNA-seq revealed upregulation of numerous desmosomal genes (DSG1, DSG3, DSC1, DSC3 and DSP) as well as KRT1 and KRT10. Additionally, P3H9-2-treated cells demonstrated downregulation of most hemidesmosomal genes. A pro-inflammatory response was not appreciated. Using pharmacological inhibitors, we identified both protein kinase C and NOTCH as key regulators of P3H9-2 induced differentiation. We lastly utilized 3D human skin equivalents to determine whether blockade of laminin α3 would lead to delayed blistering, consistent with keratinocyte differentiation. Significant blistering was noted after 72 h of treatment, with only minimal separation at 24 h. In summary, blockade of laminin α3 alters keratinocyte differentiation, representing a potential complement-independent mechanism of blistering.Sulfonylurea receptor 1 (SUR1) overexpression in the central nervous system is a potential biomarker for positron emission tomography (PET) imaging of brain damage and recovery. VU0071063, a selective ligand of SUR1 able to cross the blood-brain barrier, was isotopically radiolabeled with carbon-11 from a desmethyl precursor obtained quantitatively in one step. Ready-to-inject [11C]VU0071063 was obtained in 18 ± 2% radiochemical yield and 103 ± 22 GBq/μmol molar activity. PET imaging in healthy rats demonstrated a significant brain penetration and rapid elimination of the tracer in vivo, encouraging further investigation in animal models of SUR1 overexpression.The relationship between knee moments and markers of knee osteoarthritis progression has not been examined in different knee osteoarthritis subtypes. The objective was to examine relationships between external knee moments during gait and tibiofemoral cartilage thickness in patients with nontraumatic and posttraumatic knee osteoarthritis. For this cross-sectional study, participants with knee osteoarthritis were classified into two groups nontraumatic (n = 22; mean age 60 years) and posttraumatic (n = 19; mean age 56 years, history of anterior cruciate ligament rupture). Gait data were collected with a three-dimensional motion capture system sampled at 100 Hz and force plates sampled at 2000 Hz. External knee moments were calculated using inverse dynamics. Cartilage thickness was determined with magnetic resonance imaging (T1-weighted, 3D sagittal gradient-echo sequence). Linear regression analyses examined relationships between cartilage thickness with knee moments, group, and their interaction. A higher knee adduction moment impulse was negatively associated with medial to lateral cartilage thickness ratio (B = -1.97). This relationship differed between participants in the nontraumatic osteoarthritis group (r = -0.56) and posttraumatic osteoarthritis group (r = -0.30). A higher late stance knee extension moment was associated with greater medial femoral condyle cartilage thickness (B = -0.86) and medial to lateral cartilage thickness (B = -0.73). These relationships also differed between participants in the nontraumatic osteoarthritis group (r = -0.61 and r = -0.51, respectively) and posttraumatic osteoarthritis group (r = 0.10 and r = 0.25, respectively). Clinical Significance The relationship between knee moments with tibiofemoral cartilage thickness differs between patients with nontraumatic and posttraumatic knee osteoarthritis. The potential influence of mechanical knee loading on articular cartilage may also differ between these subtypes.
Hypoxaemia is a common concern during equine general anaesthesia. The prevalence and predictors of hypoxaemia in horses undergoing elective anaesthesia in particular are poorly documented.

To determine and compare the prevalence of hypoxaemia (defined as PaO
≤80mm Hg, on the lowest value recorded) in horses undergoing anaesthesia for exploratory laparotomy and elective procedures, and to identify risk factors in both subpopulations.

Retrospective cohort study.

Data were collected from 774 records of 708 horses undergoing general anaesthesia between April 2017 and August 2020. Potential predictors of hypoxaemia in horses undergoing anaesthesia for exploratory laparotomy or elective procedures were investigated separately by univariable penalised maximum likelihood logistic regression, followed by multivariable analysis. The lowest recorded PaO
was used as a single data point for the determination of hypoxaemia and arterial oxygen partial pressure to fractional inspired oxygen ratio analysis.

Hypoxploratory laparotomy were over six times more likely to become hypoxaemic than horses undergoing elective procedures. Bodyweight, type of procedure, and high PIP were predictors of hypoxaemia.
Model for end-stage liver disease (MELD) likely has nonlinear effects on operative outcomes. We use machine learning to evaluate the nonlinear (dependent variable may not correlate one to one with an increased risk in the outcome) relationship between MELD and outcomes of cardiac surgery.

Society of Thoracic Surgery indexed elective cardiac operations between 2011 and 2018 were included. MELD was retrospectively calculated. Logistic regression models and an imbalanced random forest classifier were created on operative mortality. Cox regression models and random forest survival models evaluated survival. Variable importance analysis (VIMP) ranked variables by predictive power. Linear and machine-learned models were compared with receiver operator characteristic (ROC) and Brier score.

We included 3872 patients. Operative mortality was 1.7% and 5-year survival was 82.1%. MELD was the fourth largest positive predictor on VIMP analysis for operative long-term survival and the strongest negative predictor for operative mortality. MELD was not a significant predictor for operative mortality or long-term survival in the logistic or Cox regressions. The logistic model ROC area was 0.762, compared to the random forest classifier ROC of 0.674. The Brier score of the random forest survival model was larger than the Cox regression starting at 2 years and continuing throughout the study period. Bootstrap estimation on linear regression demonstrated machine-learned models were superior.

MELD and mortality are nonlinear. MELD was insignificant in the Cox multivariable regression but was strongly important in the random forest survival model and when using bootstrapping, the superior utility was demonstrated of the machine-learned models.
MELD and mortality are nonlinear. MELD was insignificant in the Cox multivariable regression but was strongly important in the random forest survival model and when using bootstrapping, the superior utility was demonstrated of the machine-learned models.A strain was isolated from an activated sludge system and identified as Halomonas piezotolerans HN2 in this study, which is the first strain in H. piezotolerans with the capability of heterotrophic nitrification and aerobic denitrification. Strain HN2 showed the maximum nitrogen removal rate of 9.10 mg/L/h by utilizing ammonium at the salinity of 3.0%. Under saline environment, HN2 could remove nitrogen efficiently in neutral and slightly alkaline environments, with the carbon sources of sodium succinate and sodium citrate and the C/N ratio of 15-20, and the maximum removal efficiencies of ammonium, nitrite, and nitrate were 100%, 96.35%, and 99.7%, respectively. The genomic information revealed the presence of amoA, napA, and nosZ genes in strain HN2, and the target bands of nirS were obtained via a polymerase chain reaction. Therefore, we inferred that ammonium was mainly utilized for the growth of strain HN2 through assimilation, and another part of the initial ammonium was converted into nitrate through nitrification, and then into gaseous nitrogen through denitrification. This report indicated the potential application of strain HN2 and other nitrifying and denitrifying Halomonas strains in the removal of nitrogen pollution in marine-related environments and also implies the important role of Halomonas in the nitrogen cycle process of the ocean.Restriction fragment length polymorphism (RFLP) of mitochondrial DNA (mtDNA) had been used for molecular identification of Sporothrix spp., which is the causative fungi of sporotrichosis and the most prevalent deep-seated dermatomycosis. Also, mtDNA-RFLP had been used to investigate the molecular epidemiology of sporotrichosis. While the current standard for molecular diagnosis is performed by sequence analysis of the calmodulin gene (CAL), correspondence between the results from CAL and mtDNA is of diagnostic and epidemiological interest. BAY-876 GLUT inhibitor Here, we investigated the correspondence between CAL and mtDNA used for molecular identification of Sporothrix globosa and S. schenckii, which are two major species. We also investigated and propose molecular markers suitable to describe the epidemiology of S. globosa, which is considered as a species with few intraspecific polymorphisms. Eighty-seven strains morphologically identified as S. schenckii sensu lato were investigated. They were identified as group A (17 types, 17 strains) or B (14 types, 70 strains) by mtDNA-RFLP. Partial sequences of CAL, internal transcribed spacer, and spacer between atp9 and cox2 genes of mtDNA of these strains were determined. All group A strains corresponded to S. schenckii, and group B to S. globosa. The sequences of the amplicons targeted on the spacer region in mtDNA of S. globosa ranged 510-515 bp in length and exhibited 10 molecular variations, whereas CAL indicated seven molecular variations. In conclusion, most of the S. schenckii sensu lato strains isolated from Japanese sporotrichosis patients were confirmed as S. globosa, because group B, which comprised the majority of strains, matched perfectly with S. globosa by the CAL sequencing study. We proposed sequence variations in the spacer between atp9 and cox2 genes of mtDNA as a suitable molecular epidemiological marker for S. globosa.
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