Blood biochemistry represents a minimally invasive tool for monitoring sea turtle health, assessing injured sea turtles and supporting conservation strategies. In Grenada, West Indies, plasma biochemical variables were examined in 33 nesting leatherback (Dermochelys coriacea), 49 foraging green (Chelonia mydas), 49 foraging hawksbill (Eretmochelys imbricata) and 12 nesting hawksbill sea turtles sampled between 2017 and 2022. Plasma biochemistry reference intervals are described herein except for nesting hawksbills, which are represented by descriptive statistics due to the low sample size. Select analyte concentrations were positively correlated with curved carapace length in leatherbacks (chloride), green turtles (total protein, albumin and globulin) and foraging hawksbills (total protein, albumin and phosphorus). Cholesterol (7.8 mmol/l ± 1.6 SD) and triglyceride (6.9 mmol/l ± 1.9 SD) concentrations were significantly higher in leatherbacks compared to foraging green turtles, foraging hawksbills and nesting hawksbills (P < 0.001 for all). Cholesterol was significantly higher in nesting hawksbills compared to foraging green turtles (P = 0.050) and foraging hawksbills (P = 0.050). Foraging hawksbills demonstrated significantly higher aspartate transaminase activities than leatherbacks (P = 0.002), green turtles (P = 0.009) and nesting hawksbills (P < 0.001). Biochemical results provide baseline population health data and support guidance for treatments during clinical sea turtle rehabilitation efforts. They also provide insight into species-specific physiologic differences and preludes further studies to better characterize the impacts of life-stage class on biochemistry reference intervals to better support wild sea turtle populations in Grenada.

UNASSIGNED: Matrix metalloproteinase 7 (MMP7) has been suggested as a promising biomarker in diagnosing biliary atresia (BA). This study aimed to assess the diagnostic accuracy of serum MMP7 in BA in the Middle Eastern population.
UNASSIGNED: In this cross-sectional study, neonates and infants with direct hyperbilirubinemia admitted to Namazi referral hospital, Shiraz, Iran, were studied. Baseline demographic and clinical characteristics and blood samples were obtained on admission. MMP7 serum concentration was measured using an enzyme-linked immunosorbent assay (ZellBio GmbH, Ulm, Germany).
UNASSIGNED: 44 infants with a mean age of 65.59 days were studied. Of these patients, 13 cases were diagnosed with BA, and 31 cases\' cholestasis related to other etiologies. Serum MMP7 concertation was 2.13 ng/mL in the BA group and 1.85 ng/mL in the non-BA group. MMP7 was significantly higher in those presented with either dark urine or acholic stool. The predictive performance capability of the MMP7 was not significant in the discrimination of BA from the non-BA group based on receiver operating characteristic curve analysis (area under curve: 0.6, 95% confidence interval: 0.45-0.75). In the optimal cut of point 1.9, the sensitivity and specificity were 84.6% and 45.1%, respectively. Further combination of MMP7 with Gamma-glutamyl transferase (GGT), alkaline phosphatase, direct and total bilirubin, and dark urine or acholic stool was not remarkably boosted the diagnostic accuracy of the test. Interestingly, GGT at a cut-off point of 230 U/L was 84.6% sensitive and 90.3% specific for BA.
UNASSIGNED: Our results are not consistent with previous studies on this subject. Considering more conventional and available tests like GGT besides conducting future studies with greater samples and different geographical areas is recommended.

UNASSIGNED: Progression of alcohol-associated liver disease (ALD) is driven by genetic predisposition. The rs13702 variant in the lipoprotein lipase (LPL) gene is linked to non-alcoholic fatty liver disease. We aimed at clarifying its role in ALD.
UNASSIGNED: Patients with alcohol-associated cirrhosis, with (n = 385) and without hepatocellular carcinoma (HCC) (n = 656), with HCC attributable to viral hepatitis C (n = 280), controls with alcohol abuse without liver damage (n = 366), and healthy controls (n = 277) were genotyped regarding the LPL rs13702 polymorphism. Furthermore, the UK Biobank cohort was analysed. LPL expression was investigated in human liver specimens and in liver cell lines.
UNASSIGNED: Frequency of the LPL rs13702 CC genotype was lower in ALD with HCC in comparison to ALD without HCC both in the initial (3.9% vs. 9.3%) and the validation cohort (4.7% vs. 9.5%; p <0.05 each) and compared with patients with viral HCC (11.4%), alcohol misuse without cirrhosis (8.7%), or healthy controls (9.0%). This protective effect (odds ratio [OR] = 0.5) was confirmed in multivariate analysis including age (OR = 1.1/year), male sex (OR = 3.0), diabetes (OR = 1.8), and carriage of the PNPLA3 I148M risk variant (OR = 2.0). In the UK Biobank cohort, the LPL rs13702 C allele was replicated as a risk factor for HCC. Liver expression of LPL mRNA was dependent on LPL rs13702 genotype and significantly higher in patients with ALD cirrhosis compared with controls and alcohol-associated HCC. Although hepatocyte cell lines showed negligible LPL protein expression, hepatic stellate cells and liver sinusoidal endothelial cells expressed LPL.
UNASSIGNED: LPL is upregulated in the liver of patients with alcohol-associated cirrhosis. The LPL rs13702 high producer variant confers protection against HCC in ALD, which might help to stratify people for HCC risk.
UNASSIGNED: Hepatocellular carcinoma is a severe complication of liver cirrhosis influenced by genetic predisposition. We found that a genetic variant in the gene encoding lipoprotein lipase reduces the risk for hepatocellular carcinoma in alcohol-associated cirrhosis. This genetic variation may directly affect the liver, because, unlike in healthy adult liver, lipoprotein lipase is produced from liver cells in alcohol-associated cirrhosis.

Epigastric abdominal pain is a common indication for consultation. In the majority of cases, medical history, clinical examination and routine biological exams allow for an easy diagnosis. Sometimes the symptomatology is unusual, in which case it is essential to perform a complete clinical examination and to use various imaging techniques to search for eventual atypical causes. Membranous obstruction of inferior vena cava is a rare cause of such a phenomenon. We describe a Budd-Chiari syndrome caused by membranous obstruction of inferior vena cava in a 66-year-old woman with no medical history as a rare cause of epigastric abdominal pain. We will describe this clinical experience in the light of the literature and point out the contribution of radiological imaging in the diagnosis of this rare pathology.

Alcohol-related liver disease (ALD) represents one of the leading causes of chronic liver disease and is a major cause of liver-related deaths worldwide. ALD encompasses a range of disorders including simple steatosis, alcoholic steatohepatitis, fibrosis, cirrhosis, and hepatocellular carcinoma. Patients with underlying ALD and continued heavy alcohol consumption can also develop an episode of acute-on-chronic liver injury called alcohol-associated hepatitis, the most severe form of the disease, which portends a poor prognosis. The most important risk factor for the development of ALD is the amount of alcohol consumed. Individual susceptibility to progression to advanced fibrosis among heavy drinkers is likely determined by a combination of behavioral, environmental, genetic, and epigenetic factors, but the mechanisms are largely unknown. The only effective therapy for ALD is prolonged alcohol abstinence. Diagnosis of ALD involves assessing patients for alcohol use disorder and signs of advanced liver disease. In clinical practice, the histological assessment for ALD diagnosis is uncommon, and it is usually based on the medical history, clinical manifestations, and laboratory and imaging tests. Several promising biomarkers that can have both diagnostic and prognostic value in patients with ALD have been identified in recent years. This review provides an overview of the clinical spectrum of ALD, the diagnostic approach of the disease from different perspectives as well as current diagnostic and prognostic biomarkers.

We report the case of a 19-month-old girl with late-onset ornithine transcarbamylase (OTC) deficiency initially referred to gastroenterology for intermittent vomiting lasting a year and abnormal liver enzymes (AST 730 U/L [reference range 26-55 U/L]; ALT 1213 U/L [reference range 11-30 U/L]) without hepatomegaly. While the patient was hospitalized for liver biopsy, intermittent tremors of the upper extremities with varying severity were noted. The patient was presumed to have hyperammonemia secondary to acute liver failure and was discharged after 5 days; follow-up monitoring led to readmission 7 days later. A brain MRI showed nonspecific bilateral pericallosal and bifrontal white matter FLAIR hyperintensities. These findings raised suspicion for a metabolic disease and prompted a genetics consultation. After inconclusive biochemical testing and worsening clinical status, rapid whole genome sequencing results were obtained identifying a novel, de novo, likely pathogenic, variant c.608C > T (p.Ser203Phe) in the OTC gene. The patient was promptly started on an oral nitrogen scavenger, citrulline supplementation, and protein restriction. Ammonia and glutamine levels normalized within 1 month of treatment and have stayed within the goal ranges with continued tailoring of treatment. Her parents noted resolution of vomiting and improved mood stability. Liver enzymes normalized after 2 months of treatment. The tremor, identified as asterixis, improved and a repeat brain MRI 3 months after the initial imaging showed near-complete resolution of previous white matter hyperintensities.

UNASSIGNED: The low-phospholipid-associated cholelithiasis (LPAC) syndrome is a recently described peculiar form of cholelithiasis associated with the ATP-binding-cassette subfamily B, member 4 (ABCB4) gene deficiency. The purpose of our study was to analyse the relationship between magnetic resonance (MR) features and the genetic status of ABCB4 in people with LPAC syndrome.
UNASSIGNED: A total of 233 individuals with proven LPAC syndrome were enrolled between January 2003 and June 2018 in a retrospective single-centre study. Inclusion criteria included availability of clinical files, MR images, and genetic data. MR images were analysed by consensus among 3 senior radiologists blinded to the status of ABCB4 gene mutation.
UNASSIGNED: A total of 125 individuals (mean age at first MR imaging 40.8 years; 66% females; 48% ABCB4 variant) were included. MR abnormalities were found in 61 (49%) of the 125 individuals. Forty (67%) of the 60 individuals with an ABCB4 gene variant had MR abnormalities as compared with 21 (33%) of the 65 individuals without an ABCB4 gene variant (odds ratio [OR] 4.1, 95% CI 1.9-9.5, p = 0.0001). Compared to individuals with no variant, individuals with an ABCB4 variant were more likely to show intrahepatic macrolithiasis (56 vs. 17%; OR 6.3, 95% CI 2.6-16.2, p <0.0001), bile duct dilatation (60 vs. 18%; OR 6.5, 95% CI 2.7-16.3, p <0.0001), and at least 1 MR feature of complication (35 vs. 15%; OR 2.9, 95% CI 1.1-7.8, p <0.05).
UNASSIGNED: ABCB4-related LPAC syndrome is associated with more frequent and severe hepatobiliary MR abnormalities. This finding strongly supports the major role of the ABCB4 gene in the pathogenesis of LPAC syndrome and highlights a genotype-phenotype association in this inherited disease with genetic heterogeneity.
UNASSIGNED: ABCB4-related LPAC syndrome associated with an ABCB4 gene variant demonstrates more frequent and severe hepatobiliary MR abnormalities. This finding supports the major role of the ABCB4 gene in the pathogenesis of LPAC syndrome.

UNASSIGNED: Primary biliary cholangitis (PBC) is a chronic cholangiopathy characterised by immuno-mediated injury of interlobular bile ducts leading to intrahepatic cholestasis and progressive liver fibrosis. PBC histology is characterised by portal inflammation, progressive fibrosis, ductopenia, and the appearance of the so-called ductular reaction. The aim of the present study was to investigate the pathogenetic relevance of ductular reaction in PBC.
UNASSIGNED: Liver biopsies were collected from naïve people with PBC (N = 87). Clinical-serological parameters were obtained at diagnosis and after 1 year of ursodeoxycholic acid (UDCA) treatment. Histological staging was performed on all slides according to multiple scoring systems and criteria for PBC. Liver samples were obtained from Mdr2 -/- mice treated with or without UDCA. Samples were processed for histology, immunohistochemistry, and immunofluorescence.
UNASSIGNED: Ductular reaction in people with PBC correlated with the disease stage and liver fibrosis, but not with disease activity; an extensive ductular reaction correlated with serum alkaline phosphatase levels at diagnosis, response to UDCA, and individuals\' estimated survival, independently from other histological parameters, including disease stage. In people with PBC, reactive ductules were associated with the establishment of junctions with bile canaliculi and with fibrogenetic cell activation. Consistently, in a mouse model of intrahepatic cholestasis, UDCA treatment was effective in reducing ductular reaction and fibrosis and increasing ductular-canalicular junctions.
UNASSIGNED: Extensive ductular reaction outlines a severe histologic phenotype in PBC and is associated with an inadequate therapy response and a worse estimated prognosis.
UNASSIGNED: In people affected by primary biliary cholangitis (PBC), the histological appearance of extensive ductular reaction identifies individuals at risk of progressive fibrosis. Ductular reaction at diagnosis correlates with the lack of response to first-line therapy with ursodeoxycholic acid and serves to restore ductular-canalicular junctions in people with PBC. Assessing ductular reaction extension at diagnosis may add valuable information for clinicians.

Stratifying patients according to disease severity has been a major hurdle during the COVID-19 pandemic. This usually requires evaluating the levels of several biomarkers, which may be cumbersome when rapid decisions are required. In this manuscript we show that a single nanoparticle aggregation test can be used to distinguish patients that require intensive care from those that have already been discharged from the intensive care unit (ICU). It consists of diluting a platelet-free plasma sample and then adding gold nanoparticles. The nanoparticles aggregate to a larger extent when the samples are obtained from a patient in the ICU. This changes the color of the colloidal suspension, which can be evaluated by measuring the pixel intensity of a photograph. Although the exact factor or combination of factors behind the different aggregation behavior is unknown, control experiments demonstrate that the presence of proteins in the samples is crucial for the test to work. Principal component analysis demonstrates that the test result is highly correlated to biomarkers of prognosis and inflammation that are commonly used to evaluate the severity of COVID-19 patients. The results shown here pave the way to develop nanoparticle aggregation assays that classify COVID-19 patients according to disease severity, which could be useful to de-escalate care safely and make a better use of hospital resources.

The current work clarifies the negative effects of excess exposure to boric acid (H3BO3) as a boron-containing compound on rats and the possible ameliorative effect of melatonin (MEL). Forty rats were equally divided into 5 groups as follows: group 1 was treated as control while groups 2, 3, 4 and 5 were orally administered corn oil (0.5 ml), H3BO3 (1330 mg/kg BW), MEL (10 mg/kg BW) and H3BO3 + MEL for 28 consecutive days, respectively. At the end of the experiment, blood was sampled for biochemical and hematological analysis and tissues were collected for histopathological examination. The obtained results demonstrated that the exposure to H3BO3 induced hepatorenal dysfunctions, alterations in bone-related minerals and hormones levels, prostaglandin E2 as inflammatory mediator and hematological indices. H3BO3 induced histological alterations in the liver, kidneys, bone and skin. The co-administration of MEL with H3BO3 resulted in a significant improvement in most of the measured parameters and restoration of morpho-functional state of different organs compared to the H3BO3 group. In conclusion, the study clearly demonstrated that H3BO3- induced various adverse effects and that melatonin may be beneficial in a partial mitigating the H3BO3 and may represent a novel approach in the counteracting its toxicity.