The first Irish genome and ways of improving sequence accuracy

Whole-genome sequencing of an Irish person reveals hundreds of thousands of novel genomic variants. Imputation using previous known information improves the accuracy of low-read-depth sequencing

Maternal factors and utilization of the antenatal care services during pregnancy associated with low birth weight in rural Nepal: analyses of the antenatal care and birth weight records of the MATRI-SUMAN trial

Low birth weight (LBW) remains a major public health problem in developing countries, including Nepal. This study was undertaken to examine the association between LBW and maternal factors and antenatal care service utilization, in rural Nepal, using data obtained for a capacity-building and text-messaging intervention, designed to enhance maternal and child health service utilization among pregnant women, in rural Nepal (“MATRI-SUMAN”). The study used a clustered randomized controlled design and was conducted during 2015–2016. We investigated maternal and antenatal care service utilization determinants of LBW, using a logistic regression model. Of the four hundred and two singleton babies, included in the present study, seventy-eight (19.4%) had an LBW (mean (SD), 2210.64 (212.47)) grams. It was found that Dalit caste/ethnicity, illiteracy, manual labor, a female baby, and having more than four family members were significantly positively associated with LBW. In addition, mothers who did not visit an antenatal care (ANC) unit, visited an ANC < 4 times, did not take iron and folic acid (IFA), de-worming tablets, and mothers that did not consume additional food, during pregnancy, were more likely to have an LBW baby, than their counterparts. The MATRI-SUMAN intervention and availability of a kitchen garden at home, were found to reduce the risk of LBW. Nepalese child survival policies and programs should pay attention to these maternal and antenatal care service utilization factors, while designating preventive strategies to improve child health outcomes

Formyl-methionine as an N-degron of a eukaryotic N-end rule pathway

In bacteria, nascent proteins bear the pretranslationally generated N-terminal (Nt) formyl-methionine (fMet) residue. Nt-fMet of bacterial proteins is a degradation signal, termed fMet/N-degron. In contrast, proteins synthesized by cytosolic ribosomes of eukaryotes were presumed to bear unformylated Nt-Met. Here we found that the yeast formyltransferase Fmt1, although imported into mitochondria, could also produce Nt-formylated proteins in the cytosol. Nt-formylated proteins were strongly up-regulated in stationary phase or upon starvation for specific amino acids. This up-regulation strictly required the Gcn2 kinase, which phosphorylates Fmt1 and mediates its retention in the cytosol. We also found that the Nt-fMet residues of Nt-formylated proteins act as fMet/N-degrons, and identified the Psh1 ubiquitin ligase as the recognition component of this eukaryotic fMet/N-end rule pathway, which destroys Nt-formylated proteins

Endoscopic Removal of Inflated Transected Sengstaken–Blakemore Tube Using Endoscopic Scissors

Balloon tamponade using Sengstaken–Blakemore (SB) tube is employed as a bridging therapy in cases in which endoscopic therapy fails to control esophageal variceal bleeding. Although SB tube insertion can lead to successful hemostasis, it is accompanied by numerous complications, with SB tube transection being one of the rarest complications. A 53-year-old man with liver cirrhosis and hepatocellular carcinoma presented with massive esophageal variceal bleeding. Therapeutic endoscopic variceal ligation failed, and SB tube was inserted. The SB tube was unexpectedly disconnected because of the patient’s irritability due to hepatic encephalopathy. The esophageal and gastric balloon of the SB tube remained inflated in the stomach. Whereas the use of other endoscopic instruments was ineffective, endoscopic removal was successfully accomplished using endoscopic scissors. In conclusion, we detected SB tube transection in a patient with hepatic encephalopathy and removed remnants of the inflated tube using endoscopic scissors

HMGB1, a potential regulator of tumor microenvironment in KSHV-infected endothelial cells

High-mobility group box 1 (HMGB1) is a protein that binds to DNA and participates in various cellular processes, including DNA repair, transcription, and inflammation. It is also associated with cancer progression and therapeutic resistance. Despite its known role in promoting tumor growth and immune evasion in the tumor microenvironment, the contribution of HMGB1 to the development of Kaposi’s sarcoma (KS) is not well understood. We investigated the effect of HMGB1 on KS pathogenesis using immortalized human endothelial cells infected with Kaposi’s sarcoma-associated human herpes virus (KSHV). Our results showed that a higher amount of HMGB1 was detected in the supernatant of KSHV-infected cells compared to that of mock-infected cells, indicating that KSHV infection induced the secretion of HMGB1 in human endothelial cells. By generating HMGB1 knockout clones from immortalized human endothelial cells using CRISPR/Cas9, we elucidated the role of HMGB1 in KSHV-infected endothelial cells. Our findings indicate that the absence of HMGB1 did not induce lytic replication in KSHV-infected cells, but the cell viability of KSHV-infected cells was decreased in both 2D and 3D cultures. Through the antibody array for cytokines and growth factors, CXCL5, PDGF-AA, G-CSF, Emmprin, IL-17A, and VEGF were found to be suppressed in HMGB1 KO KSHV-infected cells compared to the KSHV-infected wild-type control. Mechanistically, phosphorylation of p38 would be associated with transcriptional regulation of CXCL5, PDGF-A and VEGF. These observations suggest that HMGB1 may play a critical role in KS pathogenesis by regulating cytokine and growth factor secretion and emphasize its potential as a therapeutic target for KS by modulating the tumor microenvironment

Long-term prognosis and the need for histologic assessment of chronic hepatitis B in the serological immune-tolerant phase

Background/Aims The histologic status of the immune-tolerant (IT) phase of chronic hepatitis B relative to long-term outcomes is unclear. This study aimed to discover how the serological criteria currently in use correspond to histologic criteria in determining the IT phase and indication for liver biopsy. Methods Patients in the serological IT phase determined by positive hepatitis B e antigen, hepatitis B virus (HBV) DNA ≥106 IU/mL, and normal or minimally elevated alanine aminotransferase (ALT) ≤60 IU/L, who underwent liver biopsy at three different hospitals were included. The distribution of the histologic IT phase, defined as fibrosis of stage 1 or less and inflammation of grade 1 or less, was compared with that of the serological IT phase. The risk factors for the incidence of liver-related events, such as hepatocellular carcinoma, liver cirrhosis, liver transplantation, and death, were also analyzed. Results Eighty-two (31.7%) out of 259 clinically suspected IT phase patients belonged to the histologic IT phase. Age over 35, high AST, and low albumin were useful for ruling out the histologic IT phase. Risk factors predicting liver-related events were age and significant fibrosis stage. There was no significant difference in the proportion of histologic IT phase and clinical prognosis between normal ALT and mildly elevated ALT groups. However, even in patients with normal ALT, age was an important factor in predicting the presence of the histologic IT phase. Conclusions A significant number of patients who belonged to the serological IT phase were not in the histologic IT phase. Patients over 35 years and those with high AST, low albumin, and low HBV DNA levels were more likely to experience poor long-term clinical outcomes. Therefore, additional histologic assessment should be considered

Impact of successful restoration of sinus rhythm in patients with atrial fibrillation and acute heart failure: Results from the Korean Acute Heart Failure registry

Background: Restoring and maintaining sinus rhythm (SR) in patients with atrial fibrillation (AF) failed to show superior outcomes over rate control strategies in prior randomized trials. However, there is sparse data on their outcomes in patients with acute heart failure (AHF).Methods: From December 2010 to February 2014, 5,625 patients with AHF from 10 tertiary hospitals were enrolled in the Korean Acute Heart Failure registry, including 1,961 patients whose initial electrocardiogram showed AF. Clinical outcomes of patients who restored SR by pharmacological or electrical cardioversion (SR conversion group, n = 212) were compared to those of patients who showed a persistent AF rhythm (AF persistent group, n = 1,662).Results: All-cause mortality both in-hospital and during the follow-up (median 2.5 years) were significantly lower in the SR conversion group than in the AF persistent group after adjustment for risk factors (adjusted hazard ratio [HR]; 95% confidence interval [CI] = 0.26 [0.08–0.88], p = 0.031 and 0.59 [0.43–0.82], p = 0.002, for mortality in-hospital and during follow-up, respectively). After 1:3 propensity score matching (SR conversion group = 167, AF persistent group = 501), successful restoration of SR was associated with lower all-cause mortality (HR [95% CI] = 0.68 [0.49–0.93], p = 0.015), heart failure rehospitalization (HR [95% CI] = 0.66 [0.45–0.97], p = 0.032), and composite of death and heart failure rehospitalization (HR [95% CI] = 0.66 [0.51–0.86], p = 0.002).Conclusions: Patients with AHF and AF had significantly lower mortality in-hospital and during follow-up if rhythm treatment for AF was successful, underscoring the importance of restoring SR in patients with AHF

Prevalence of behavioral risk factors of cardiovascular diseases and associated socio-economic factors among pregnant women in a rural area in Southern Nepal

Background: Cardiovascular diseases (CVDs) have dramatically infiltrated populations living in abject poverty in Low- and Middle-income Countries (LMICs), and poor maternal and child health outcomes have been frequently reported for those with CVD risk factors. However, few studies have explored the behavioral risk factors of CVDs among pregnant women in rural settings. This study aimed at determining the prevalence and identifying the socio-economic predictors of behavioral risk factors of CVDs among pregnant women in rural area in Southern Nepal. Methods: A Community-based cross-sectional study was conducted in 52 clusters of Dhanusha District of Nepal in a total of 426 pregnant women in their second trimester using multistage cluster sampling method. Multivariable logistic regression model was used to assess independent associations between behavioral risk factors during pregnancy and maternal socio-economic characteristics. Results: Of the 426 study participants, 86.9, 53.9, 21.3 and 13.3%, respectively, reported insufficient fruits and vegetables consumption, insufficient physical activity, tobacco use, and harmful alcohol drinking. Socio-economic factors significantly associated with more than one behavioral risk factors in expectant mothers with a primary level education (adjusted odds ratio (AOR) 2.78; 95% Confidence Interval (CI) (1.35–5.72)), 20–34 years age group (Adjusted Odds Ratio (AOR) 0.27; 95% CI (0.13–0.56)), and those with the highest wealth index (AOR 0.36; 95% CI (0.16–0.84)). Conclusion: Higher prevalence of behavioral risk factors for CVDs and their socio-economic factors prevailing among pregnant women living in rural Nepal call for immediate health promotion interventions such as community awareness and appropriate antenatal counseling