Compositions of gut microbiota before and shortly after hepatitis C viral eradication by direct antiviral agents.
It is unclear whether dysbiosis in hepatitis C virus (HCV) infected patients results from the viral infection per se or develops as a result of hepatic dysfunction. We aimed to characterize compositions in gut microbiome before and shortly after HCV clearance. In this prospective cohort study, adult patients with confirmed HCV viremia were screened before receiving direct antiviral agents. Those with recent exposure to antibiotics or probiotics (within one month), prior abdominal surgery, or any malignancy were ineligible. Stool was collected before antiviral therapy started and at 12 weeks after the treatment completed. From the extracted bacterial DNA, 16 s rRNA gene was amplified and sequenced. Each patient was matched 1:2 in age and sex with uninfected controls. A total of 126 individuals were enrolled into analysis. The gut microbiome was significantly different between HCV-infected patients (n = 42), with or without cirrhosis, and their age-and sex-matched controls (n = 84) from the levels of phylum to amplicon sequence variant (all p values < 0.01 by principal coordinates analysis). All patients achieved viral eradication and exhibited no significant changes in the overall composition of gut microbiome following viral eradication (all p values > 0.5), also without significant difference in alpha diversity (all p values > 0.5). For the purpose of exploration, we also reported bacteria found differently abundant before and after HCV eradication, including Coriobacteriaceae, Peptostreptococcaceae, Staphylococcaceae, Morganellaceae, Pasteurellaceae, Succinivibrionaceae, and Moraxellaceae. Gut microbiota is altered in HCV-infected patients as compared with uninfected controls, but the overall microbial compositions do not significantly change shortly after HCV eradication.


An alternative domain determines nuclear localization in multifunctional protein 4.1.
Multiple protein 4.1 isoforms are originated by alternative pre-mRNA splicing, differential use of two translation initiation sites, and posttranslational modifications. The complexity of alternative splicing events suffered by the 4.1 pre-mRNA makes necessary the direct cloning of 4.1 full-coding cDNA sequences to ensure that the encoded 4.1 proteins are naturally occurring isoforms. We have approached this point by reverse transcription-polymerase chain reaction techniques using RNA from the nucleated human Molt-4 T-cell line as a starting template. Molecular cloning of 4.1 cDNAs using the second translation initiation codon has allowed us to identify two 4.1 isoforms, designated 4.1H and 4.1I, which are differentially targeted to the nucleus (4.1H) and the cytoplasm (4.1I). These two isoforms differ only in the inclusion (4.1H) or exclusion (4.1I) of 21 amino acids encoded by exon 16. A cluster of basic amino acids, KKKR, generated by joining of the sequences encoded by the constitutive exon 13 and the alternative exon 16, is necessary for the nuclear targeting of 4.1H, as demonstrated by site-directed mutagenesis analysis. Immunofluorescence microscopy and biochemical studies indicate that 4.1H belongs to the group of nuclear 4.1 proteins that are distributed diffusely throughout the nucleoplasm and that are extractable in 0.5% Triton X-100. This is the first demonstration of differential nuclear targeting by the presence of an alternative domain, among naturally occurring protein 4.1 isoforms.


[A new method in fetal heart electrophysiology - fetal magnetocardiography].
Fetal magnetocardiography (fMCG) is used as a non-invasive method for registering the electrophysiological fetal heart activity. Superconducting quantum interference device-based magnetometers are currently used to make fMCG recordings. In contrast to fetal ECG, this method is independent of signal loss due to isolating factors such as, especially, the vernix caesaroa between the 27th and 34th weeks of gestation. We report about a term newborn with a third degree AV block, examined by this method.


Dietary betaine intake is associated with skeletal muscle mass change over 3 years in middle-aged adults: the Guangzhou Nutrition and Health Study.
A higher dietary intake or serum concentration of betaine has been associated with greater lean body mass in middle-aged and older adults. However, it remains unknown whether betaine intake is associated with age-related loss of skeletal muscle mass (SMM). We assessed the association between dietary betaine intake and relative changes in SMM after 3 years in middle-aged adults. A total of 1242 participants aged 41-60 years from the Guangzhou Nutrition and Health Study 2011-2013 and 2014-2017 with body composition measurements by dual-energy X-ray absorptiometry were included. A face-to-face questionnaire was used to collect general baseline information. After adjustment for potential confounders, multiple linear regression found that energy-adjusted dietary betaine intake was significantly and positively associated with relative changes (i.e. percentage loss or increase) in SMM of legs, limbs and appendicular skeletal mass index (ASMI) over 3 years of follow-up (β 0·322 (se 0·157), 0·309 (se 0·142) and 0·303 (se 0·145), respectively; P < 0·05). The ANCOVA models revealed that participants in the highest betaine tertile had significantly less loss in SMM of limbs and ASMI and more increase in SMM of legs over 3 years of follow-up, compared with those in the bottom betaine tertile (all Ptrend < 0·05). In conclusion, our findings suggest that elevated higher dietary betaine intake may be associated with less loss of SMM of legs, limbs and ASMI in middle-aged adults.


Serological diagnosis of congenital toxoplasmosis.
A comparison of the indirect haemagglutination test (IHAT) with the dye test (DT) in 23 infants with congenital toxoplasmosis showed that in the early part of the first year of life the IHAT titres were nearly all lower than the DT titres. In six cases the IHAT was negative or the titre was so low that the cases could have been missed in routine screening. Later in the first year the IHAT titres became higher than the DT and remained so. The infants belonging to mothers with a high IHAT and therefore assumed to have become infected early in pregnancy had severe infections which included all the cases of hydrocephalus. Infants of mothers with low IHAT titres relative to the DT and therefore thought to have been infected later in pregnancy had generalized, mild or subclinical infection. With some difficulty a suitable commercial conjugated anti-IgM serum was found that gave positive results in immunofluorescent antibody tests for specific IgM antibody with all the infected infants and their mothers throughout the first year and negative results in uninfected infants and their mothers.


Continuous inhaled nitric oxide therapy in a case of sickle cell disease with multiorgan involvement.
A 27-year-old female with sickle cell disease (HbSS) was admitted presenting with severe bone pain and fever. She refused blood transfusions throughout her hospital stay for religious reasons. During the first 9 days of admission, the patient's clinical presentation became worse despite antibiotic coverage. The patient exhibited pulmonary infiltrates and mild hypertension, increased pain, fever, tachycardia, and decreased hematocrit. After day 8 of admission, her laboratory findings and clinical presentation indicated that her disease was markedly worse. With the patient's consent, inhaled nitric oxide therapy (iNO = 40 ppm) was initiated and continued for 3.2 days. After a full day of iNO therapy, the clinical improvement was limited to temperature normalization and stabilization of her hemoglobin levels. After 2 more days of iNO therapy, her multiple clinical complications of sickle cell disease improved markedly and she was discharged 3 days after completion of the iNO treatment. The complications of NO therapy, such as methemoglobulinemia or decreased blood pressure, were not detected during the iNO therapy. Although limited to a single individual, we propose that our anecdotal experience suggests that iNO therapy may (i) need to be continuous for several days to provide improved benefits, (ii) treat several of sickle cell complications besides pain, and (iii) exhibit few complications. These proposals need to be confirmed in clinical trials.