Alcoholic hepatitis in females

In the period 1970-1984 alcoholic hepatitis was diagnosed by liver biopsy in 52 females. Thirty-six patients with cirrhosis were generally in a worse clinical and biochemical state than those without cirrhosis. Biochemical tests for liver function showed significant improvement from admission to the time of liver biopsy. At follow-up liver function tests were generally better in patients who had stopped drinking alcohol compared to those who continued to do so. The 5-year survival rate was 82% for females without cirrhosis, and 45% for those with cirrhosis (p less than 0.03). Considering the sex-related differences in alcohol abuse in the general population we found no evidence of increased susceptibility to the hepatotoxic effect of alcohol in females.     

Experimental verification of a model describing the occupied volume by polymers in solution

A relation is proposed which yields the occupied volume by macromolecular chains in solution. The experimental verification of the model is carried out by a viscometric study of the ternary system polymer A/polymer B/solvent. More precisely the viscometric study permits the determination of the critical concentration c^** corresponding to the incipient overlap of spherical coils.     

An HLA study in 74 Danish haemochromatosis patients and in 21 of their families

HLA-A and -B alleles in 74 Danish patients and 21 homozygous relatives with idiopathic haemochromatosis (IH) were compared with those in a sample of 1719 chromosomes from healthy Danish control subjects. The following alleles occurred with higher frequencies in IH compared to controls: A3: 53.6% vs. 15.1% (Pc less than 0.001); B7: 33.1% vs. 15.6% (Pc less than 0.001); B14: 6.9% vs. 3.0% (Pc greater than 0.05); B38: 5% vs. 0.9% (Pc greater than 0.05); B47: 4.0% vs. 0.4% (Pc greater than 0.05). Pedigree analyses disclosed 19 different haplotypes in IH subjects, compared to 286 haplotypes in controls. The following haplotypes occurred with higher frequency in IH compared to controls: A3,B5: 10.3% vs. 0.3% (Pc less than 0.001); A3,B7: 25.6% vs. 6.6% (Pc = 0.001); A3,B14: 3.4% vs. 0.6% (Pc greater than 0.05); A3,B47: 6.9% vs. 0.2% (Pc greater than 0.05). The major IH marker HLA-A3 was found in 56% of the haplotypes. The patterns of HLA-alleles associated with IH in Denmark show similarities to those in Central Europe, Australia, USA and Canada, being A3,B7 dominated and those in Central Sweden, England and Ireland, being A3,B14 dominated.     

Evidence that the Cys282Tyr mutation of the HFE gene originated from a population in Southern Scandinavia and spread with the Vikings

Hereditary hemochromatosis has been recognized as a clinical disorder for more than 100 years. The common form of the disorder is caused by the Cys282Tyr mutation (C282Y) of the HFE gene. Hereditary hemochromatosis affects predominantly people of Northern European origin. The C282Y mutation probably occurred on a single chromosome carrying the ancestral hemochromatosis haplotype, which subsequently was spread by emigration and the founder effect. It has been estimated that the C282Y mutation appeared 60-70 generations ago. It was initially suggested that the ancestral C282Y mutation occurred within the Celtic group of peoples. However, we hypothesize that the distribution of the C282Y mutation in Europe is more consistent with an origin among the Germanic Iron Age population in Southern Scandinavia. From this area, the mutation could later be spread by the migratory activities of the Vikings. The aim of the present study was to evaluate the validity of these two hypotheses. Several arguments are in favor of the 'Viking hypothesis': first, the highest frequencies (5.1-9.7%) of the C282Y mutation are observed in populations in the Northern part of Europe, i.e. Denmark, Norway, Sweden, Faeroe Islands, Iceland, Eastern part of England (Danelaw) and the Dublin area, all Viking homelands and settlements. Second, the highest allele frequencies are reported among populations living along the coastlines. Third, the frequencies of the C282Y mutation decline from Northern to Southern Europe. Intermediate allele frequencies (3.1-4.8%) are seen in the populations in Central Europe, which is the original Celtic homeland. Low allele frequencies (0-3.1%) are recognized in populations in Southern Europe and the Mediterranean.     

HLA class II (DR, DQ, DP) in patients with sarcoidosis: evidence of an increased frequency of DRw6.

The distribution of HLA class II (DR, DQ, and DP) antigens was studied in 41 patients with symptomatic sarcoidosis (SA) and ethnically matched healthy controls. HLA-DR, -DQw1 and -DQw3 typings were performed with alloantisera in the conventional microcytotoxic test, whereas -DP typings were done using primed lymphocyte typing. The frequencies of DRw6 were 41.5% in SA patients and 17.9% in controls (relative risk, RR = 3.2, p = 0.00087, p less than 0.05 when corrected). DR3 was decreased to 14.6% in SA patients compared to 25.9% in controls (RR = 0.49, p = 0.07, i.e., not statistically significant). The decreased frequency of DR3 was only seen in patients with severe, long-standing disease. In contrast, the DRw6 increase was most pronounced in patients with severe disease (RR = 6.4; p = 0.003). There were no statistically significant deviations in the frequencies of DQ and DP alleles between patients and controls. In conclusion, our data suggest that DRW6 confers susceptibility and DR3 resistance to severe, long-standing disease.     

Association of sleep duration and quality with immunological response after vaccination against severe acute respiratory syndrome coronavirus-2 infection

Growing evidence suggests that sleep could affect the immunological response after vaccination. The aim of this prospective study was to investigate possible associations between regular sleep disruption and immunity response after vaccination against coronavirus disease 2019 (COVID-19). In total, 592 healthcare workers, with no previous history of COVID-19, from eight major Greek hospitals were enrolled in this study. All subjects underwent two Pfizer–BioNTech messenger ribonucleic acid (mRNA) COVID-19 vaccine BNT162b2 inoculations with an interval of 21 days between the doses. Furthermore, a questionnaire was completed 2 days after each vaccination and clinical characteristics, demographics, sleep duration, and habits were recorded. Blood samples were collected and anti-spike immunoglobulin G antibodies were measured at 20 ± 1 days after the first dose and 21 ± 2 days after the second dose. A total of 544 subjects (30% males), with median (interquartile range [IQR]) age of 46 (38–54) years and body mass index of 24·84 (22.6–28.51) kg/m² were eligible for the study. The median (IQR) habitual duration of sleep was 6 (6–7) h/night. In all, 283 participants (52%) had a short daytime nap. In 214 (39.3%) participants the Pittsburgh Sleep Quality Index score was >5, with a higher percentage in women (74·3%, p < 0.05). Antibody levels were associated with age (r = −0.178, p < 0.001), poor sleep quality (r = −0.094, p < 0.05), insomnia (r = −0.098, p < 0.05), and nap frequency per week (r = −0.098, p < 0.05), but after adjusting for confounders, only insomnia, gender, and age were independent determinants of antibody levels. It is important to emphasise that insomnia is associated with lower antibody levels against COVID-19 after vaccination.     

Modified CLSI Extended-Spectrum β-Lactamase (ESBL) Confirmatory Test for Phenotypic Detection of ESBLs among Enterobacteriaceae Producing Various β-Lactamases

The worldwide dissemination of Enterobacteriaceae producing AmpC β-lactamases and carbapenemases makes difficult the phenotypic detection of extended-spectrum β-lactamases (ESBLs), as they may be masked by these additional enzymes. A modification of the CLSI ESBL confirmatory test was developed and evaluated in a comparative study for its ability to successfully detect ESBLs among Enterobacteriaceae producing various carbapenemases (Klebsiella pneumoniae carbapenemase [KPC], VIM, NDM, and OXA-48) and plasmidic or derepressed AmpCs. The modified CLSI ESBL confirmatory test was performed with cefotaxime and ceftazidime disks with and without clavulanate, on which both boronic acid (BA) and EDTA were dispensed. A total of 162 genotypically confirmed ESBL-positive Enterobacteriaceae isolates (83 carbapenemase/ESBL producers, 25 AmpC/ESBL producers, and 54 ESBL-only producers) were examined. For comparison, 139 genotypically confirmed ESBL-negative Enterobacteriaceae isolates (94 of them possessed carbapenemases and 20 possessed AmpCs) were also tested. The standard CLSI ESBL confirmatory test was positive for 106 of the 162 ESBL producers (sensitivity, 65.4%) and showed false-positive results for 4 of the 139 non-ESBL producers (specificity, 97.1%). The modified CLSI ESBL confirmatory test detected 158 of 162 ESBL producers (sensitivity, 97.5%) and showed no false-positive results for non-ESBL producers (specificity, 100%). The findings of the study demonstrate that the modified CLSI ESBL confirmatory test using antibiotic disks containing both BA and EDTA accurately detects ESBLs in Enterobacteriaceae regardless of the coexistence of additional β-lactam resistance mechanisms.     

One-year recombinant growth hormone therapy does not improve hemoglobin state and morphology of erythrocytes in growth hormone deficient children

An increase in growth rates of children suffering from growth hormone deficiency (GHD) subjected to recombinant growth hormone treatment (rGHT) was shown to be accompanied by acceleration of metabolic processes that may stimulate oxygen consumption in various organs and tissues. Therefore, oxygen-transporting properties of RBC should undergo considerable changes during the rGHT. The aim of this study was to examine the effects of rGHT on erythrocyte shape and hemoglobin state in GHD children. The level of oxyhemoglobin (Oxy-Hb) in RBC was analyzed by Raman spectroscopy. The RBC count, mean corpuscular hemoglobin (MCH), mean corpuscular volume (MCV) and other parameters were calculated. The blood of eleven treatment-naive prepubertal children with GHD (aged 3–9, median 5.7 years) was examined and compared with control group (aged 5–7; median 6.0 years) at three time points: 0, 3 and 12 months of rGHT. Before rGHT, the MI in GHD children was higher (median 0.48 vs 0.14 p = 0.0018) and the RBC count was lower (median 4.20 vs 4.96 10¹² cells/L p = 0.0022) than in control group. After the treatment, cell count in GHD patients did not differ significantly from the control group, but Oxy-Hb level became higher (median 0.64 vs 0.41 p = 0.0075). During rGHT, MCV decreased (median 80.3 vs 83.2 μm³ p = 0.0231). Morphological and functional characteristics of erythrocytes in GHD children were shown to differ significantly from the healthy control group. A twelve-month rGHT partially improved some of the studied parameters but Oxy-Hb level and echinocyte count remained high.     

RET,a targetable driver of pancreatic adenocarcinoma

Pancreatic ductal adenocarcinoma (PDA) remains a deadly disease, affecting about 40,000 individuals in the United States annually. We aimed to characterize the role of RET as a co-driver of pancreas tumorigenesis. To assess the role of RET as a co-driver of PDA, we generated a novel triple mutant transgenic mouse based on the cre-activated p53^R172H gene and a constitutively active RET ^M919T mutant (PRC). Survival analysis was performed using Kaplan–Meier analysis. Study of human PDA specimens and Pdx-1-Cre/Kras^G12D /p53^R172H (KPC) mice revealed that RET is upregulated during pancreas tumorigenesis, from inception through precursor lesions, to invasive cancer. We demonstrated that activation of RET is capable of inducing invasive pancreatic carcinomas in the background of the P53 inactivation mutation. Compared to KPC mice, PRC animals had distinct phenotypes, including longer latency to tumor progression, longer survival, and the presence of multiple macrometastases. Enhanced activation of the MAPK pathway was observed as early as the PanIN 2 stage. Sequencing of the exonic regions of KRAS in PRC-derived PDA cells revealed no evidence of KRAS mutations. RET can be an essential co-driver of pancreatic tumorigenesis in conjugation with KRAS activity. These data suggest that RET may be a potential target in the treatment of PDA.     

Characterization and Management of Arrhythmic Events in Young Patients With Brugada Syndrome

Background

Information on young patients with Brugada syndrome (BrS) and arrhythmic events (AEs) is limited.