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Previously, we showed that tear fluid protects corneal epithelial cells against Pseudomonas aeruginosa without suppressing bacterial viability. Here, we studied how tear fluid affects bacterial gene expression.

RNA-sequencing was used to study the P. aeruginosa transcriptome after tear fluid exposure (5h, 37

C). Outcomes were further investigated by biochemical and physiological perturbations to tear fluid and tear-like fluid (TLF) and assessment of bacterial viability following tear/TLF pretreatment and antibiotic exposure.

Tear fluid deregulated ~180 P. aeruginosa genes ≥8 fold versus PBS including downregulating lasI, rhlI, qscR (quorum sensing/virulence), oprH, phoP, phoQ (antimicrobial resistance) and arnBCADTEF (polymyxin B resistance). Upregulated genes included algF (biofilm formation) and hemO (iron acquisition). qPCR confirmed tear down-regulation of oprH, phoP and phoQ. Tear fluid pre-treatment increased P. aeruginosa resistance to meropenem ~5-fold (4μg/ml), but enhanced polymyxin B susceptoteinase K sensitive component(s) to enhance P. aeruginosa sensitivity to polymyxin B.

The lacrimal exocrinopathy of primary Sjögren’s syndrome (pSS) is one of the main causes of severe dry eye syndrome and a burden for patients. Early recognition and treatment could prevent irreversible damage to lacrimal glands. The aim of this study was to find biomarkers in tears, using metabolomics and data mining approaches, in patients with newly-diagnosed pSS compared to other causes of dry eye syndrome.

A prospective cohort of 40 pSS and 40 non-pSS Sicca patients with dryness was explored through a standardized targeted metabolomic approach using liquid chromatography coupled with mass spectrometry. A metabolomic signature predictive of the pSS status was sought out using linear (logistic regression with elastic-net regularization) and non-linear (random forests) machine learning architectures, after splitting the studied population into training, validation and test sets.

Among the 104 metabolites accurately measured in tears, we identified a discriminant signature composed of nine metabolites (two amino acids serine, aspartate; one biogenic amine dopamine; six lipids Lysophosphatidylcholine C161, C181, C182, sphingomyelin C160 and C223, and the phoshatidylcholine diacyl PCaa C424), with robust performances (ROC-AUC=0.83) for predicting the pSS status. Adjustment for age, sex and anti-SSA antibodies did not disrupt the link between the metabolomic signature and the pSS status. The non-lipidic components also remained specific for pSS regardless of the dryness severity.

Our results reveal a metabolomic signature for tears that distinguishes pSS from other dry eye syndromes and further highlight nine key metabolites of potential interest for early diagnosis and therapeutics of pSS.

Our results reveal a metabolomic signature for tears that distinguishes pSS from other dry eye syndromes and further highlight nine key metabolites of potential interest for early diagnosis and therapeutics of pSS.

Adult spinal deformity (ASD) surgeries are complex, involving long operative times and surgical morbidity. It is currently unclear how the invasiveness of ASD surgery compares to other major operations.

To (1) develop a quantitative score of surgical morbidity and invasiveness, and (2) compare this score between ASD surgery and other major operations.

Retrospective review of prospectively collected data.

A prospective surgical registry was used to identify all patients undergoing ASD surgery involving ≥ 7 segments. Seventeen additional procedures were included coronary artery bypass grafting (CABG), pancreatectomy, and esophagectomy, among others.

Perioperative factors (operative time, transfusions, ventilation) and complications were collected and combined with a previously validated Postoperative Morbidity Survey to create a Surgical Invasiveness and Morbidity Score (SIMS).

Computed scores were compared across surgeries using Welch’s t-test. Multiple linear regression modeling was used to compartrolling for important perioperative factors. These data have implications for patient counseling, resource allocation, and informed consent.Reprogramming non-cardiomyocytes (non-CMs) into cardiomyocyte (CM)-like cells is a promising strategy for cardiac regeneration in conditions such as ischemic heart disease. Here, we used a modified mRNA (modRNA) gene delivery platform to deliver a cocktail of four cardiac-reprogramming genes (Gata4 (G), Mef2c (M), Tbx5 (T) and Hand2 (H)) together with three reprogramming-helper genes (Dominant Negative (DN)-TGFβ, DN-Wnt8a and Acid ceramidase (AC)), termed 7G-modRNA, to induce CM-like cells. We showed that 7G-modRNA reprogrammed 57% of CM-like cells in vitro. Through a lineage-tracing model, we determined that delivering the 7G-modRNA cocktail at the time of myocardial infarction reprogrammed ∼25% of CM-like cells in the scar area and significantly improved cardiac function, scar size, long-term survival and capillary density. Mechanistically, we determined that while 7G-modRNA cannot create de-novo beating CMs in vitro or in vivo, it can significantly upregulate pro-angiogenic mesenchymal stromal cells markers and transcription factors. We also demonstrated that our 7G-modRNA cocktail leads to neovascularization in ischemic-limb injury, indicating CM-like cells importance in other organs besides the heart. modRNA is currently being used around the globe for vaccination against COVID-19, and this study proves this is a safe, highly efficient gene delivery approach with therapeutic potential to treat ischemic diseases.

In situ contouring is one of the surgical techniques used for scoliosis reduction. The initial correction could change over time, with deterioration of the sagittal balance. The purpose of this study was to analyze the loss of correction after degenerative lumbar scoliosis surgery using in situ contouring.

Full spine radiographs of 73 patients (mean age 63.3 years, mean follow-up 27 months) were analyzed before surgery, after surgery, and at the final follow-up. The following radiographic parameters were measured C2-C7 lordosis, T4-T12 kyphosis, L1-S1 lordosis, pelvic tilt, pelvic incidence, sacral slope, SVA C7, SVA C2, Cobb angle. Bayesian inference was used to compare the changes in these parameters. A probability>0.95 was considered as a significant change.

After surgery, lumbar lordosis increased from -28.4° to -37.8° (probability 0.999), then decreased to -32.1° at the final follow-up (probability 0.953). Thoracic kyphosis increased from 29.6° to 37.4° after surgery (probability 1.00) and continued to increase to 41.6° at the final follow-up (probability 0.999). SVA C7 increased from 38.5mm to 62.3mm (probability 0.999) and pelvic tilt from 19.4° to 25.1° (probability 1.00) during the follow-up period. Ten patients had to be reoperated because of a surgical site infection. Infection (14%) was associated with an increase of SVA C7 (probability 0.989) and thoracic kyphosis (probability 0.987). Nonunion (16%) was associated with a decrease in lumbar lordosis (probability 0.756).

Correction of degenerative lumbar scoliosis by in situ contouring resulted in sagittal balance correction; however, some of this correction was lost during the follow-up period. The main risk factors were deep wound infection and nonunion.

IV, Retrospective study.

IV, Retrospective study.In this study, effects of different concentrations (0, 5, 10, 20, 30, and 40 mg/L) of glyphosate-based herbicide (GBH) on Nile tilapia (Oreochromis niloticus) were investigated after a 14-day of exposure. After determination of LC50 value, effects of GBH on hematological and serum biochemical parameters in blood samples, DNA damage, lipid peroxidation and catalase activity in liver tissues, expression levels of antioxidant enzyme-related genes (SOD, CAT, GPx, and GST) and immune-related genes (TGF-β, TGF-α and IL1-β) were evaluated. The LC50 value has been found as 44.4 mg/L for GBH. GBH exposure at all concentrations caused alterations in blood parameters. Brepocitinib in vivo GBH induced oxidative stress in liver and DNA damage in blood. Antioxidant enzyme-related genes were significantly up-regulated to suppress oxidative stress. On the other hand, the expression levels of immune-related genes decreased in fish exposure to particularly ≥20 mg/L GBH.Primary sclerosing cholangitis (PSC) is a rare and chronic cholestatic liver disease of unknown cause commonly associated with inflammatory bowel disease (IBD) and characterized by progressive obliterative fibro-inflammation of the biliary tree. Although the natural course is highly variable, PSC is often progressive, leading to biliary cirrhosis and its complications. In addition, PSC is a condition harbouring broad neoplastic potential with increased susceptibility for the development of both biliary and colon cancer. As in other chronic liver diseases, non-invasive methods play a major role in the diagnosis and monitoring of PSC. link2 MR cholangiography is the key exam for the diagnosis and has replaced diagnostic endoscopic retrograde cholangiopancreatography (ERCP). A strict and standardised protocol for carrying out MR cholangiography is recommended. Liver stiffness measured by FibroScan® correlates with the degree of liver fibrosis, has a prognostic value and should be repeated during follow-up. Invasive methods still play an important role, especially ERCP which is indicated for therapeutic purposes or for endo-biliary sample collection in suspected cholangiocarcinoma (following discussion in a multidisciplinary team meeting) and total colonoscopy which is recommended at the initial diagnosis of any PSC and annually in patients with IBD.

ICIs are used in the management of several malignancies. However, they can result in immune-related adverse events, such as colitis. link3 The aim of this study is to obtain an epidemiological survey of patients who develop immune checkpoint inhibitor (ICI)-induced colitis and identify underlying risk factors.

A cohort study was performed using Explorys, a US-based population database. Our cohort included all patients in a five-year interval on an ICI. We further identified those who developed colitis after initiating an ICI. Demographic data and possible risk factors were assessed. Odds ratios were calculated and multivariable statistical analysis was performed.

3.6% of patients developed ICI-induced colitis. Women , Caucasians , individuals older than 65 years , obese patients , and those with a history of alcohol abuse were more likely to develop colitis. Patients who received Nivolumab , Ipilimumab , Pembrolizumab , and Atezolizumab had an increased odds of developing colitis. The majority of cases were diagnosed in the first 6 months of therapy.

This is the largest study to describe the epidemiology of ICI-induced colitis and it is the first to identify underlying risk factors. Ipilimumab poses the greatest risk for ICI-induced colitis. The risk of colitis should be discussed with all patients prior to initiating an ICI, as it may be a factor in choosing among ICIs.

This is the largest study to describe the epidemiology of ICI-induced colitis and it is the first to identify underlying risk factors. Ipilimumab poses the greatest risk for ICI-induced colitis. The risk of colitis should be discussed with all patients prior to initiating an ICI, as it may be a factor in choosing among ICIs.