S-allylcysteine Improves Blood Flow Recovery and Prevents Ischemic Injury by Augmenting Neovasculogenesis.

Studies suggest that a low level of circulating human endothelial progenitor cells (EPCs) is a risk factor for ischemic injury and coronary artery disease (CAD). Consumption of S-allylcysteine (SAC) is known to prevent CAD. However, the protective effects of SAC on the ischemic injury are not yet clear. In this study, we examined whether SAC could improve blood flow recovery in ischemic tissues through EPC-mediated neovasculogenesis. The results demonstrate that SAC significantly enhances the neovasculogenesis of EPCs in vitro. The molecular mechanisms for SAC enhancement of neovasculogenesis include the activation of Akt/endothelial nitric oxide synthase signaling cascades. SAC increased the expression of c-kit, β-catenin, cyclin D1, and Cyclin-dependent kinase 4 (CDK4) proteins in EPCs. Daily intake of SAC at dosages of 0.2 and 2 mg/kg body weight significantly enhanced c-kit protein levels in vivo. We conclude that dietary consumption of SAC improves blood flow recovery and prevents ischemic injury by inducing neovasculogenesis in experimental models

Therapeutic Lung Lavage with Diluted Surfactant in Neonates with Severe Meconium Aspiration Syndrome

Meconium aspiration syndrome (MAS) may result in considerable morbidity and mortality in newborn infants. The current standard treatment is still in need of improvement for the most severe patients. We report 3 cases with devastating MAS that was successfully treated with therapeutic lung lavage. These cases were all delivered in local obstetrics clinics or hospitals with meconium-stained amniotic fluid and non-vigorous appearance at birth. However, no endotracheal suction was performed when they were born. All of them suffered from severe hypoxia and unstable vital signs despite there being high ventilatory settings when they were transferred to the tertiary medical center. Therapeutic lung lavage with diluted surfactant (Survanta, 5 mg/mL, 30 mL/kg in 2 aliquots) was performed within 24 hours of age. Bloody fluid (about 40–50% of total lavage amount) was recovered in all 3 cases. Although brief desaturation and bradycardia were observed during the procedures, 2 of them tolerated the procedures well and improved soon after lavage. The other patient received lung lavage in a relatively unstable condition and needed chest tapping to relieve bilateral pleural effusion. Their respiratory condition improved after the procedures, and they were all discharged within 1 month without major respiratory complications. These successful experiences are compatible with previous animal studies and other case reports with different lavage protocols. We conclude that therapeutic lung lavage may improve the outcome in newborn infants with severe MAS, and there were no significant adverse side effects observed. Before performing lung lavage, stabilization and optimal support may prevent unexpected results during and after lavage

Hyperbilirubinemia with urinary tract infection in infants younger than eight weeks old

AbstractBackgroundHyperbilirubinemia is one of the most common causes for hospital admission in neonatal infants. Previous studies have found that jaundice may be one of the initial symptoms related to urinary tract infection (UTI) in infants. This study is to evaluate the incidence and related factors of neonatal infants with the initial presentation of hyperbilirubinemia and final diagnosis of UTI in a tertiary teaching hospital.MethodsWe retrospectively investigated the medical records of admitted infants younger than 8 weeks old with hyperbilirubinemia between January and December 2008. The jaundiced infants having tests of urinalysis were enrolled into our study and grouped into UTI or no UTI group according to the findings of urinary culture.ResultsA total of 217 neonatal jaundiced infants were enrolled. Among them, 12 cases (5.5%) were grouped into the UTI group, and the most common cultured bacterium from their urine was Escherichia coli. There was no significant difference in the babies’ birth weight, maternal conditions, or total bilirubin levels between the two groups. There was also no significant difference between the two groups in their admission age (9.7 ± 13.5 days vs. 6.1 ± 6.7 days in UTI and no UTI groups, respectively) or the ratio of outpatients (50% vs. 25% in UTI and no UTI groups, respectively) (p > 0.05). The cases of UTI group had significantly lower hemoglobin (15.2 ± 2.7 g/dL vs. 17.2 ± 2.3 g/dL, respectively) and higher formula feeding rate (8.3% vs. 2.9%, respectively) than the no UTI group (p < 0.05).ConclusionThe incidence of UTI in the admitted infants with hyperbilirubinemia was as high as approximately 5.5%. The most common cultured bacterium in urine was E coli. Therefore, performing urinary tests to exclude the possibility of coincidental UTI may be necessary for admitted jaundiced infants younger than 8 weeks old

Differential early diagnosis of benign versus malignant lung cancer using systematic pathway flux analysis of peripheral blood leukocytes

Early diagnosis of lung cancer is critically important to reduce disease severity and improve overall survival. Newer, minimally invasive biopsy procedures often fail to provide adequate specimens for accurate tumor subtyping or staging which is necessary to inform appropriate use of molecular targeted therapies and immune checkpoint inhibitors. Thus newer approaches to diagnosis and staging in early lung cancer are needed. This exploratory pilot study obtained peripheral blood samples from 139 individuals with clinically evident pulmonary nodules (benign and malignant), as well as ten healthy persons. They were divided into three cohorts: original cohort (n = 99), control cohort (n = 10), and validation cohort (n = 40). Average RNAseq sequencing of leukocytes in these samples were conducted. Subsequently, data was integrated into artificial intelligence (AI)-based computational approach with system-wide gene expression technology to develop a rapid, effective, non-invasive immune index for early diagnosis of lung cancer. An immune-related index system, IM-Index, was defined and validated for the diagnostic application. IM-Index was applied to assess the malignancies of pulmonary nodules of 109 participants (original + control cohorts) with high accuracy (AUC: 0.822 [95% CI: 0.75–0.91, p < 0.001]), and to differentiate between phases of cancer immunoediting concept (odds ratio: 1.17 [95% CI: 1.1–1.25, p < 0.001]). The predictive ability of IM-Index was validated in a validation cohort with a AUC: 0.883 (95% CI: 0.73–1.00, p < 0.001). The difference between molecular mechanisms of adenocarcinoma and squamous carcinoma histology was also determined via the IM-Index (OR: 1.2 [95% CI 1.14–1.35, p = 0.019]). In addition, a structural metabolic behavior pattern and signaling property in host immunity were found (bonferroni correction, p = 1.32e − 16). Taken together our findings indicate that this AI-based approach may be used for “Super Early” cancer diagnosis and amend the current immunotherpay for lung cancer

Airway Microbiota Dynamics Uncover a Critical Window for Interplay of Pathogenic Bacteria and Allergy in Childhood Respiratory Disease.

Repeated cycles of infection-associated lower airway inflammation drive the pathogenesis of persistent wheezing disease in children. In this study, the occurrence of acute respiratory tract illnesses (ARIs) and the nasopharyngeal microbiome (NPM) were characterized in 244 infants through their first five years of life. Through this analysis, we demonstrate that >80% of infectious events involve viral pathogens, but are accompanied by a shift in the NPM toward dominance by a small range of pathogenic bacterial genera. Unexpectedly, this change frequently precedes the detection of viral pathogens and acute symptoms. Colonization of illness-associated bacteria coupled with early allergic sensitization is associated with persistent wheeze in school-aged children, which is the hallmark of the asthma phenotype. In contrast, these bacterial genera are associated with "transient wheeze" that resolves after age 3 years in non-sensitized children. Thus, to complement early allergic sensitization, monitoring NPM composition may enable early detection and intervention in high-risk children

A cytoplasmic RNA virus generates functional viral small RNAs and regulates viral IRES activity in mammalian cells

The roles of virus-derived small RNAs (vsRNAs) have been studied in plants and insects. However, the generation and function of small RNAs from cytoplasmic RNA viruses in mammalian cells remain unexplored. This study describes four vsRNAs that were detected in enterovirus 71-infected cells using next-generation sequencing and northern blots. Viral infection produced substantial levels (\u3e105 copy numbers per cell) of vsRNA1, one of the four vsRNAs. We also demonstrated that Dicer is involved in vsRNA1 generation in infected cells. vsRNA1 overexpression inhibited viral translation and internal ribosomal entry site (IRES) activity in infected cells. Conversely, blocking vsRNA1 enhanced viral yield and viral protein synthesis. We also present evidence that vsRNA1 targets stem-loop II of the viral 5′ untranslated region and inhibits the activity of the IRES through this sequence-specific targeting. Our study demonstrates the ability of a cytoplasmic RNA virus to generate functional vsRNA in mammalian cells. In addition, we also demonstrate a potential novel mechanism for a positive-stranded RNA virus to regulate viral translation: generating a vsRNA that targets the IRES

Perturbative instabilities in Horava gravity

We investigate the scalar and tensor perturbations in Horava gravity, with and without detailed balance, around a flat background. Once both types of perturbations are taken into account, it is revealed that the theory is plagued by ghost-like scalar instabilities in the range of parameters which would render it power-counting renormalizable, that cannot be overcome by simple tricks such as analytic continuation. Implementing a consistent flow between the UV and IR limits seems thus more challenging than initially presumed, regardless of whether the theory approaches General Relativity at low energies or not. Even in the phenomenologically viable parameter space, the tensor sector leads to additional potential problems, such as fine-tunings and super-luminal propagation.Comment: 21 pages, version published at Class. Quant. Gra

Neonatal genetics of gene expression reveal potential origins of autoimmune and allergic disease risk

Abstract: Chronic immune-mediated diseases of adulthood often originate in early childhood. To investigate genetic associations between neonatal immunity and disease, we map expression quantitative trait loci (eQTLs) in resting myeloid cells and CD4+ T cells from cord blood samples, as well as in response to lipopolysaccharide (LPS) or phytohemagglutinin (PHA) stimulation, respectively. Cis-eQTLs are largely specific to cell type or stimulation, and 31% and 52% of genes with cis-eQTLs have response eQTLs (reQTLs) in myeloid cells and T cells, respectively. We identified cis regulatory factors acting as mediators of trans effects. There is extensive colocalisation between condition-specific neonatal cis-eQTLs and variants associated with immune-mediated diseases, in particular CTSH had widespread colocalisation across diseases. Mendelian randomisation shows causal neonatal gene expression effects on disease risk for BTN3A2, HLA-C and others. Our study elucidates the genetics of gene expression in neonatal immune cells, and aetiological origins of autoimmune and allergic diseases