This case - control study aims to evaluate Procalcitonin (PCT) plasma concentrations in healthy and hospitalized cows with a conclusive diagnosis of inflammation due to bacterial infection. Thirty-four healthy and 131 sick cows were included. Procalcitonin concentrations were assessed using an ELISA kit for cattle. Depending on whether sick cows received antimicrobial treatments prior to admission or not, they were divided in treated (TP) or not treated (NTP) subgroups. Mann-Whitney U tests were performed to determine differences between healthy vs sick cows, while Kruskal-Wallis with Dunn\'s multiple comparison test were applied for healthy vs sick subgroups. Receiver operating characteristic (ROC) analysis was performed to assess the optimal cut-off value. Kaplan-Meier survival curves were determined for cows belonging to the groups with PCT values below and above ROC cut-offs. Plasma PCT concentration was 200.1 (147.8-324.1) pg/mL and 361.6 (239.7-947.1) pg/mL in the healthy control and in the sick group, respectively (P < 0.001). The optimal cut-off value of plasma PCT concentration was 244.4 pg/mL (sensitivity 73.6%, specificity 60.0%). The plasma PCT concentration was 267.5 (210.3-771.2) pg/mL in the TP subgroup and 425.6 (253.1-1242) pg/mL in the NTP subgroup (P = 0.03). Cows with PCT above the ROC cut-off value had a reduced survival percentage and a higher mortality risk (P < 0.05). Procalcitonin showed the ability of differentiate healthy cows from hospitalized cows with a conclusive diagnosis of inflammation due to bacterial infection. Moreover, PCT was a good predictor of negative prognostic outcome.

Zinc is known to have a critical role in the maintenance of intestinal homeostasis, immune cells, and anti-diarrheal and anti-inflammatory actions.
The aim of this study was to evaluate the correlation between zinc status with serum zonulin and gastrointestinal symptoms in diarrhea-predominant patients with irritable bowel syndrome (IBS-D).
This case-control study included 61 newly diagnosed IBS-D patients and 61 healthy matched controls. Dietary zinc intake, serum zinc, and zonulin levels were measured. IBS severity was evaluated using the IBS severity score system (IBS-SSS) questionnaire.
Serum zinc levels were lower in the IBS-D group compared with the controls (p = 0.001). Serum zinc was negatively correlated with serum zonulin in IBS-D patients (r = - 0.271; p = 0.035). Also, a reverse association between the serum zinc and odds of IBS-D was found [OR = 0.979; 95% CI (0.966-0.992)].
Our results suggest that zinc may have a role in the pathogenesis of IBS. However, clinical trial studies are warranted to evaluate this finding.

A 67-year-old man visited his doctor because of anorexia and was diagnosed with gastric cancer based on endoscopic findings. Endoscopy revealed a 0-Ⅰ type tumor, 6 cm in size, at the gastric angle. Preoperative CT showed no apparent lymph node or distant metastases. Distal gastrectomy was performed for gastric cancer with Billroth Ⅰ reconstruction. He had no complications and was discharged on postoperative day 11. The pathological Stage was pT2N0M0, pStage ⅠB, and he underwent no adjuvant chemotherapy. Four months postoperatively, serum CA19-9, AFP, and PIVKA-Ⅱ were elevated, and CT revealed multiple liver tumors. A liver biopsy was performed for the definitive diagnosis. The patient was diagnosed with liver metastases from gastric cancer. It is considered that AFP and PIVKA-Ⅱ were produced by the liver metastasis from gastric cancer. He received chemotherapy for liver metastasis and died 1 year after the recurrence.

Secondary sclerosing cholangitis in critically ill patients (SC-CIP) occurs after long-term intensive care treatment. This study aimed to assess the gut-liver axis in SC-CIP. Stool microbiome composition, gut permeability, bacterial translocation and serum bile acid profiles of 18 SC-CIP patients compared to 11 patients after critical illness without liver disease (CIP controls), 21 patients with cirrhosis and 21 healthy controls were studied. 16S rDNA was isolated from stool and sequenced using the Illumina technique. Diamine oxidase, zonulin, soluble CD14 (sCD14) and lipopolysaccharide binding protein were measured in serum and calprotectin in stool. Serum bile acids were analyzed by high-performance liquid chromatography-mass spectrometry (HPLC-MS). Reduced microbiome alpha diversity and altered beta diversity were seen in SC-CIP, CIP controls and cirrhosis compared to healthy controls. SC-CIP patients showed a shift towards pathogenic taxa and an oralization. SC-CIP, CIP controls and cirrhotic patients presented with impaired gut permeability, and biomarkers of bacterial translocation were increased in SC-CIP and cirrhosis. Total serum bile acids were elevated in SC-CIP and cirrhosis and the bile acid profile was altered in SC-CIP, CIP controls and cirrhosis. In conclusions, observed alterations of the gut-liver axis in SC-CIP cannot solely be attributed to liver disease, but may also be secondary to long-term intensive care treatment.

There is an accumulation in studies which strive to reveal zonulin\'s potential role in mental disorders. To date, one cross-sectional recent study examined zonulin in patients with bipolar disorders (BDs); however, its role still remains vague due to high fluctuation. Our aims are to determine plasma zonulin levels in exacerbation and treatment response periods, and to examine the associations between zonulin and symptom severity in BD. 30 patients with BD type I and 29 healthy controls participated in the current study. Socio-demographic form, Young Mania Rating Scale (YMRS), and Hamilton Depression Rating Scale (HAM-D) were administered. Enzyme-linked immune assay (ELISA) method was used to measure the plasma zonulin levels of the participants. The groups did not differ in plasma zonulin-level comparisons. Plasma zonulin did not alter between the exacerbation and treatment response periods of the patients. Besides, no associations were found between plasma zonulin-level and disease symptoms. Intestinal barrier integrity was not found to be altered among patients with BD type I. The lack of alterations in plasma zonulin level between different periods may be attributable to several factors. One possible factor might be the ELISA method which can detect other proteins (e.g., properdin) rather than zonulin. Therefore, it might fail to indicate direct observation of intestinal permeability. However, future study designs with more accurate estimation of zonulin in a larger sample may provide a different perspective on intestinal permeability\'s possible role in BD etiology.

We report a case of a 75-year-old man with a-fetoprotein(AFP)-producing gastric cancer accompanied by multiple large liver metastases. The patient underwent a total gastrectomy for gastric cancer(p-T3N3H0P0M0, fStage ⅢB). The patient then underwent chemotherapy(TS-1 80m g/day)following the radical operation. However, 5 months after the radical operation, he presented with multiple large liver tumors, which were subsequently biopsied. Based on immunohistochemical examination, the liver tumors were negative for AFP protein, but were similar to hepatoid adenocarcinoma, and no fibrosis was observed in the background liver. Therefore, we diagnosed the tumors as liver metastases of AFP producing gastric cancer and metachronous liver metastasis. The patient underwent transcatheter arterial chemoembolization(TACE). TACE decreased the AFP and PIVKA-Ⅱ levels and reduced the multiple huge liver metastases. Due to the increase in AFP and the multiple liver metastases, despite intensive hepatic infusion chemotherapy, he died 5 months after admission.

There are two forms of diabetes insipidus, central (neurohypophyseal), and nephrogenic, caused by pathogenic variants in the AVP gene and the AVPR2 or AQP2 genes, respectively. We report on a four-generation family, seven individuals had central diabetes insipidus (CDI) and the female index patient seen from age 16 to 26 years had (mild) nephrogenic diabetes insipidus. In her father with CDI, a known pathogenic heterozygous AVP variant c.232_234del p.(Glu78del) was identified, confirming the diagnosis of CDI in him and the other affected family members. In the proband, molecular analysis disclosed a novel heterozygous AVPR2 gene variant, c.962A > T p.(Asn321Ile) and an extremely skewed X-inactivation, confirming X-linked nephrogenic diabetes insipidus (XL-NDI). Whole exome sequencing showed no further causative mutation. This is the first report on the co-existence of CDI and NDI in one family. Our review of symptomatic female AVPR2 heterozygotes includes 23 families with at least one affected female (including this study). There were 21 different causative mutations. Mutation types in females did not differ from those in males. Both severe XL-NDI and mild forms were reported in females. All six females with severe XL-NDI had complete loss-of-function (null) mutations. The remaining 17 female probands had milder XL-NDI caused by 14 missense variants and three null variants of the AVPR2 gene. X-inactivation was studied in nine of these females; all showed extreme or slight skewing. The review underlines that XL-NDI in female AVPR2 heterozygotes is always accompanied by skewed X-inactivation, emphasizing a need for X-inactivation studies in these females.

Recent state-of-the-art analyses in insect phylogeny have exclusively used very large datasets to elucidate higher-level phylogenies. We have tested an alternative and novel approach by evaluating the potential phylogenetic signals of identified and relatively short neuropeptide precursor sequences with highly conserved functional units. For that purpose, we examined available transcriptomes of 40 blattodean species for the translated amino acid sequences of 17 neuropeptide precursors. Recently proposed intra-ordinal relationships of Blattodea, based on the analysis of 2370 protein-coding nuclear single-copy genes (Evangelista et al., 2019), were corroborated with maximum support. The functionally different precursor units were analyzed separately for their phylogenetic information. Although the degree of information was different in the different sequence motifs, all precursor units contained phylogenetic informative data at the ordinal level, and their separate analysis did not reveal contradictory topologies. This study is the first comprehensive exploitation of complete neuropeptide precursor sequences of arthropods in such a context and demonstrates the applicability of these rather short but conserved sequences for an alternative, fast and simple analysis of phylogenetic relationships.

BACKGROUND Hepatocellular carcinoma (HCC) is a common primary hepatic cancer. Regardless of its metastatic potential, metastasis to skeletal muscle is rare, especially to one solitary muscle. The diagnostic efficiency of Protein induced by Vitamin K absence/antagonist-II (PIVKA-II) has been illustrated sufficiently and it has been proven that PIVKA-II is a potent biomarker and independent of alpha-fetoprotein (AFP). The present report describes a case of solitary muscle metastasis with PIVKA-II elevation. CASE REPORT An 81-year-old man noticed a growing mass in the proximal posterior thigh, and it was found to be a solitary tumor in the biceps femoris muscle. He had undergone a medial segmentectomy for primary HCC and transcatheter arterial chemoembolization for an intrahepatic recurrence 7 and 4 years before, respectively. The level of PIVKA-II was elevated to 11 400 mAU/mL, but the alpha-fetoprotein (AFP) level was normal. Elevation of PIVKA-II to over 50 mAU/mL had been observed 7 months before the muscular lesion was first observed. When the solitary metastasis was diagnosed, a wide resection was performed in the same way as for primary sarcoma, and the PIVKA-II value decreased to 71 mAU/mL. No recurrence at the muscle was observed, but multiple lung metastases were seen and the PIVKA-II was elevated to 1410 mAU/mL 4 months after the resection. CONCLUSIONS Resection of the solitary muscle metastasis helped control the local metastatic lesion and helped with ability to perform daily activities, as well as possibly prolonging survival. PIVKA-II is an important biomarker for HCC surveillance in conjunction with alpha-fetoprotein (AFP). PIVKA-II can be independent of AFP. Examination of the whole body is still necessary in cases with elevated PIVKA-II in order to detect extrahepatic metastasis.

BACKGROUND: Alterations of the small-intestinal permeability (s-IP) might play an essential role in both diarrhoea-predominant IBS (D-IBS) and celiac disease (CD) patients. Our aims were to analyse in D-IBS patients the symptom profile along with the levels of urinary sucrose (Su), lactulose (La), mannitol (Ma), and circulating biomarkers (zonulin, intestinal fatty acid binding protein - I-FABP, and diamine oxidase - DAO) of the gastrointestinal (GI) barrier function. The pro-inflammatory interleukins 6 and 8 (IL-6 and IL-8), the plasma values of lipopolysaccharide (LPS), and Toll-like receptor 4 (TLR-4) were also investigated. Besides, these biomarkers were compared with those in CD and healthy controls (HC). Finally, comparisons were performed between D-IBS patients with [D-IBS(+)] and without [D-IBS(-)] increased s-IP according to normal or altered La/Ma ratio.
METHODS: The study included 39 D-IBS patients, 32 CD patients, and 20 HC. GI permeability was assayed by high-performance liquid chromatography determination in the urine of Su and La/Ma ratio. ELISA kits assayed circulating concentrations of zonulin, I-FABP, DAO, IL-6, IL-8, LPS, and TLR-4. The Mann-Whitney or the Kruskal-Wallis with Dunn\'s post-test was used to assess differences among the groups.
RESULTS: As for the La/Ma ratio, %Su, and I-FABP levels, D-IBS patients were significantly different from CD, but not HC. IL-6 levels were significantly higher in CD than HC, whereas IL-8 levels were significantly higher in both D-IBS and CD patients than HC. By opposite, LPS, and TLR-4 concentrations did not differ significantly among the groups. When D-IBS patients were categorised according to normal or altered s-IP, D-IBS(+) patients had %La, %Su, I-FABP, and DAO levels significantly higher than D-IBS(-) ones. The inflammatory parameters and markers of bacterial translocation (namely, IL-6 and LPS) were significantly higher in D-IBS(+) patients than D-IBS(-) ones.
CONCLUSIONS: The present study suggests that two distinct D-IBS subtypes could be identified. The investigation of possible s-IP alterations (i.e., considering the La/Ma ratio) might be useful to assess better and categorise this heterogeneous D-IBS population.
BACKGROUND: NCT01574209 . Registered March 2012. First recruitment started in April 2012.