EuCd_{2}As_{2}: A Magnetic Semiconductor.

EuCd_{2}As_{2} is now widely accepted as a topological semimetal in which a Weyl phase is induced by an external magnetic field. We challenge this view through firm experimental evidence using a combination of electronic transport, optical spectroscopy, and excited-state photoemission spectroscopy. We show that the EuCd_{2}As_{2} is in fact a semiconductor with a gap of 0.77 eV. We show that the externally applied magnetic field has a profound impact on the electronic band structure of this system. This is manifested by a huge decrease of the observed band gap, as large as 125 meV at 2 T, and, consequently, by a giant redshift of the interband absorption edge. However, the semiconductor nature of the material remains preserved. EuCd_{2}As_{2} is therefore a magnetic semiconductor rather than a Dirac or Weyl semimetal, as suggested by ab initio computations carried out within the local spin-density approximation.

Immunoinflammatory processes: Overlapping mechanisms between obesity and eating disorders?

Obesity and eating disorders are conditions that involve eating behaviors and are sometimes comorbid. Current evidence supports alterations in immunoinflammatory processes in both obesity and eating disorders. A plausible hypothesis is that immunoinflammatory processes may be involved in the pathophysiology of obesity and eating disorders. The aim of this review is to highlight the link between obesity and eating disorders, with a particular focus on immunoinflammatory processes. First, the relation between obesity and eating disorders will be presented, followed by a brief review of the literature on their association with immunoinflammatory processes. Second, developmental factors will be discussed to clarify the link between obesity, eating disorders, and immunoinflammatory processes. Genetic and epigenetic risk factors as well as the potential roles of stress pathways and early life development will be presented. Finally, implications of these findings for future research are discussed. This review highlighted biological and developmental aspects that overlap between obesity and EDs, emphasizing the need for biopsychosocial research approaches to advance current knowledge and practice in these fields.

Testing for Hepatitis C Virus Infection Among Adults Aged ≥18 in the United States, 2013-2017.

OBJECTIVE: Approximately 2.4 million people in the United States are living with hepatitis C virus (HCV) infection. The objective of our study was to describe demographic and socioeconomic characteristics, liver disease-related risk factors, and modifiable health behaviors associated with self-reported testing for HCV infection among adults. METHODS: Using data on adult respondents aged ≥18 from the 2013-2017 National Health Interview Survey, we summarized descriptive data on sociodemographic characteristics and liver disease-related risk factors and stratified data by educational attainment. We used weighted logistic regression to examine predictors of HCV testing. RESULTS: During the study period, 11.7% (95% CI, 11.5%-12.0%) of adults reported ever being tested for HCV infection. Testing was higher in 2017 than in 2013 (adjusted odds ratio [aOR] = 1.27; 95% CI, 1.18-1.36). Adults with ≥some college were significantly more likely to report being tested (aOR = 1.60; 95% CI, 1.52-1.69) than adults with ≤high school education. Among adults with ≤high school education (but not adults with ≥some college), those who did not have health insurance were less likely than those with private health insurance (aOR = 0.78; 95% CI, 0.68-0.89) to get tested, and non-US-born adults were less likely than US-born adults to get tested (aOR = 0.77; 95% CI, 0.68-0.87). CONCLUSIONS: Rates of self-reported HCV testing increased from 2013 to 2017, but testing rates remained low. Demographic characteristics, health behaviors, and liver disease-related risk factors may affect HCV testing rates among adults. HCV testing must increase to achieve hepatitis C elimination targets.

A varying-coefficient model for gap times between recurrent events.

Recurrent events often arise in follow-up studies where a subject may experience multiple occurrences of the same type of event. Most regression models for recurrent events consider the time scale measured from the study origin and assume constant effects of covariates. In many applications, however, gap times between recurrent events are of natural interest and moreover the effects may actually vary over time. In this article, we propose a marginal varying-coefficient model for gap times between recurrent events that allows for the intra-individual correlation between events. Estimation and inference procedures are developed for the varying coefficients. Consistency and weak convergence of the proposed estimator are established. Monte Carlo simulation studies demonstrate that the proposed method works well with practical sample sizes. The proposed method is illustrated with an analysis of bladder tumor clinical data.

Dynamic regression with recurrent events.

Recurrent events often arise in follow-up studies where a subject may experience multiple occurrences of the same event. Most regression models with recurrent events tacitly assume constant effects of covariates over time, which may not be realistic in practice. To address time-varying effects, we develop a dynamic regression model to target the mean frequency of recurrent events. We propose an estimation procedure which fully exploits observed data. Consistency and weak convergence of the proposed estimator are established. Simulation studies demonstrate that the proposed method works well, and two real data analyses are presented for illustration.

Effectiveness of technology-enhanced learning in Endodontic education: a systematic review and meta-analysis.

The aim of the present systematic review was to evaluate the effectiveness of technology-enhanced learning (TEL) in the field of Endodontics to improve educational outcomes compared to traditional learning methods. Randomized controlled studies published in English were identified from two electronic databases (PubMed and Scopus) up to May 2018. Two authors independently performed study selection, data extraction and assessed the risk of bias (ROB). Any teaching method using TEL was considered as the intervention, and this was compared to traditional methods. The outcome measuring the effectiveness of learning activities was evaluated by Kirkpatrick's four-level training evaluation model. The four levels of training outcomes are as follows: Reaction, Learning, Behaviour and Results. A meta-analysis was performed to estimate the standardized mean difference (SMD) by the random effects model. In total, 13 studies were included in the systematic review. Only three studies were assessed as 'low' ROB. A meta-analysis could not be performed in the domains of Reaction and Behaviour. No significant difference was observed in knowledge gain (Learning domain) between TEL and traditional methods (SMD, 0.14 (95% CI -0.10 to 0.39) I2  = 62.7%). Similarly, no difference was observed in performance (Behaviour domain). A variable response was found in attitude (Reaction domain). From the available evidence, it can be concluded that TEL is equally as effective as traditional learning methods.

A high-resolution anorectal manometry parameter based on integrated pressurized volume: A study based on 204 male patients with constipation and 26 controls.

BACKGROUND: Conventional anorectal manometric parameters based on linear waves cannot properly predict balloon expulsion (BE) time. We aimed to determine the correlation between integrated pressurized volume (IPV) parameters during simulated evacuation (SE) and BE time in healthy individuals and constipated patients and to assess the correlation between each parameter and symptoms. METHODS: A total of 230 male participants (including 26 healthy volunteers and 204 chronically constipated patients) underwent high-resolution anorectal manometry (HRAM) and BE tests. The IPV was calculated by multiplying the amplitude, distance, and time from the HRAM profile. Receiver operating characteristic curve (ROC) analysis and partial least square regression (PLSR) were performed. KEY RESULTS: ROC analysis indicated that the IPV ratio between the upper 1 cm and lower 4 cm of the anal canal was more effective for predicting BE time (area under the curve [AUC]: 0.74, 95% confidence interval [CI]: 0.67-0.80, P < .01) than the conventional anorectal parameters, including defecation index and rectoanal gradient (AUC: 0.60, 95% CI: 0.52-0.67, P = .01). PLSR analysis of a linear combination of IPV parameters yielded an AUC of 0.79. Moreover, the IPV ratio showed a greater clinical correlation with patient symptoms than conventional parameters. CONCLUSIONS AND INFERENCES: The IPV parameters and the combination of IPV parameters via PLSR were more significantly correlated with BE time than the conventional parameters. Thus, this study presents a useful diagnostic tool for the evaluation of pathophysiologic abnormalities in dyssynergic defecation using IPV and BE time.

An unusual cause of food-induced anaphylaxis in mothers.

BACKGROUND: Galacto-oligosaccharides (GOS) are prebiotics added to commercial milk formula of infants and mothers. In recent years, cases of allergy related to GOS in atopic children have been reported in the South East Asian region. CASE PRESENTATIONS: We describe a series of pregnant (n = 4) and lactating mothers (n = 2) who developed anaphylactic reactions after consumption of maternal milk formula containing GOS. All six subjects had pre-existing atopy and a positive skin prick test to GOS and 5/5 of the subjects who were tested had positive basophil activation tests to GOS. All of the mothers and their babies had normal neonatal outcomes after the reactions. CONCLUSIONS: The supplementation of GOS into milk and beverages in the Asian region should take into account the rare chance of allergenicity of GOS in the atopic population.

Oil sands tailings ponds harbour a small core prokaryotic microbiome and diverse accessory communities.

Oil sands tailings ponds store the waste slurry generated by extracting bitumen from surface-mined oil (tar) sands ores. The ponds support diverse microbial communities involved in element cycling, greenhouse gas production, and hydrocarbon biodegradation that influence pond management and their environmental footprint. Since previous reports indicate that there are similar microbial metabolic functions amongst ponds, analogous microbiomes may be expected but ponds actually harbour distinct communities. Partial 16S rRNA gene pyrotag sequences from 95 samples were obtained from six ponds managed by three operators. From these we discerned a core prokaryotic microbiome, a subset of microbes shared amongst different samples, defined as operational taxonomic units (OTUs) at the lowest taxonomic level identifiable in individual ponds and pooled pond datatsets. Of the ∼1500-2700 OTUs detected per pond, 4-10 OTUs were shared among ≥75% of the samples per pond, but these few OTUs represented 39-54% of the ponds' sequence reads. Only 2-5 OTUs were shared by the majority of samples from all ponds. Thus the prokaryotic communities within these ponds consist of a few core taxa and numerous accessory members that likely afford resiliency and functional redundancy including roles in iron-, nitrogen- and sulfur-cycling, syntrophy, fermentation, and methanogenesis.

Sublingual immunotherapy in patients with house dust mite allergic rhinitis: prospective study of clinical outcomes over a two-year period.

BACKGROUND: Sublingual immunotherapy in patients with allergic rhinitis sensitised to house dust mites is safe, but its efficacy is controversial and sublingual immunotherapy with Blomia tropicalis has not yet been studied. This study sought to evaluate the efficacy of sublingual immunotherapy with house dust mite extract in children and adults with house dust mite allergic rhinitis over a period of two years. METHODS: A prospective observational study was conducted of children and adults diagnosed with house dust mite allergic rhinitis who were treated with sublingual immunotherapy from 2008 to 2012. Total Nasal Symptom Scores, Mini Rhinoconjunctivitis Quality of Life scores and medication usage scores were assessed prospectively. RESULTS: Thirty-nine patients, comprising 24 children and 15 adults, were studied. Total Nasal Symptom Scores and Mini Rhinoconjunctivitis Quality of Life scores dropped significantly at three months into therapy, and continued to improve. Medication usage scores improved at one year into immunotherapy. CONCLUSION: Sublingual immunotherapy with house dust mite extracts, including B tropicalis, is efficacious as a treatment for patients with house dust mite allergic rhinitis.

Anaphylaxis to galacto-oligosaccharides--an evaluation in an atopic population in Singapore.

Anaphylaxis to galacto-oligosaccharides (GOS), a prebiotic, has been described in atopic patients following its supplementation in commercial milk formula in South-East Asia. The epidemiology of this usual allergy to a carbohydrate is unknown. This study evaluated the prevalence of allergy to two formulations of commercial GOS, Vivinal™ GOS (vGOS) and Oligomate™ , in an atopic cohort. Atopic subjects (n = 487) from two specialist allergy clinics were surveyed via structured questionnaire and underwent skin prick tests to GOS. Subjects with positive skin prick tests to GOS (n = 30, 6.2%) underwent basophil activation tests, and a subset (n = 13) underwent oral challenge tests to both formulations of GOS. Six subjects had positive challenges to vGOS; and none to Oligomate. By extrapolating the BAT and oral challenge results, the prevalence of allergy to vGOS is estimated at up to 3.5% (95% CI 2.2-5.5%) of our atopic population. Our findings show that GOS allergy may be common amongst atopics in Singapore.

LincRNA-p21 acts as a mediator of ING1b-induced apoptosis.

ING1b is a tumor suppressor that affects transcription, cell cycle control and apoptosis. ING1b is deregulated in disease, and its activity is closely linked to that of p53. In addition to regulating protein-coding genes, we found that ING1b also influences the expression of large intergenic non-coding RNAs (lincRNAs). In particular, lincRNA-p21 was significantly induced after DNA-damage stress or by ING1b overexpression. Furthermore, lincRNA-p21 expression in response to DNA damage was significantly attenuated in cells lacking ING1b. LincRNA-p21 is also a target of p53 and can trigger apoptosis in mouse cell models. We found that this function of lincRNA-p21 is conserved in human cell models. Moreover, ING1b and p53 could function independently to influence lincRNA-p21 expression. However, their effects become more additive under conditions of stress. In particular, ING1b regulates lincRNA-p21 levels by binding to its promoter and is required for induction of lincRNA-p21 by p53. The ability of ING1b to cause apoptosis is also impaired in the absence of lincRNA-p21. Surprisingly, deletion of the ING1b plant homeodomain, which allows it to bind histones and regulate chromatin structure, did not alter regulation of lincRNA-p21. Our findings suggest that ING1b induces lincRNA-p21 expression independently of histone 3 lysine 4 trimethylation mark recognition and that lincRNA-p21 functions downstream of ING1b. Thus, regulation at the level of lincRNA-p21 may represent the point at which ING1b and p53 pathways converge to induce apoptosis under specific stress conditions.

Late diagnosis of intestinal malrotation treated with gastrojejunal bypass : a case report.

We report the case of a male African patient who presented at day 8 of life with recurrent episodes of proximal small intestine occlusion, which was treated conservatively, because of misdiagnosis. Physical and cognitive development was normal throughout with, however, some episodes of stagnation. At the age of 15 years the recurrence of symptoms, not responding to the current conservative treatment, resulted in severe weight loss with BMI at 11 kg/m(2). The œsogastroduodenal barium study disclosed an extrinsic duodenal compression compatible with a congenital duodenal band. Because of the major concerns related to the patient and to the medical environment, jejunostomy for feeding was first performed to improve his weight. A year later the intestinal malrotation was cured by gastrojejunal bypass. The postoperative clinical course was favorable. The patient resumed a normal life and schooling. His BMI is currently 21.5 kg/m(2).

Inelastic neutron scattering study of a nonmagnetic collapsed tetragonal phase in nonsuperconducting CaFe2As2: evidence of the impact of spin fluctuations on superconductivity in the iron-arsenide compounds.

The relationship between antiferromagnetic spin fluctuations and superconductivity has become a central topic of research in studies of superconductivity in the iron pnictides. We present unambiguous evidence of the absence of magnetic fluctuations in the nonsuperconducting collapsed tetragonal phase of CaFe2As2 via inelastic neutron scattering time-of-flight data, which is consistent with the view that spin fluctuations are a necessary ingredient for unconventional superconductivity in the iron pnictides. We demonstrate that the collapsed tetragonal phase of CaFe2As2 is nonmagnetic, and discuss this result in light of recent reports of high-temperature superconductivity in the collapsed tetragonal phase of closely related compounds.

Reliability of acute illness dihydrorhodamine-123 testing for chronic granulomatous disease.

BACKGROUND: Dihydrorhodamine (DHR) flow cytometric analysis is used to evaluate granulocyte oxidative bursts and is the test of choice for the diagnosis of chronic granulomatous disease (CGD). We present the clinical and DHR test profiles of five subjects assessed during and after acute illness. METHODS: This was a retrospective report of the findings of five out of a total of one hundred and seventeen patients, whose blood was sent to the laboratory for dihydrorhodamine-123 flow cytometry testing between January 2005 and December 2010. Using whole blood technique and stimulation using phorbol myristate acetate, the results of DHR were expressed as stimulation index and coefficient of variation of histograms of stimulated cells and compared with healthy controls. DHR tests were repeated when the patients had recovered and were clinically well. RESULTS: These five patients showed abnormal DHR test results during their acute illness, with a stimulation index (SI) lower (p = 0.009) and coefficient of variation (CV) higher (p = 0.009) than controls. The DHR profiles repeated when patients had recovered showed normalization of tests with no significant difference for SI (p = 0.602) and CV (p = 0.917) compared to controls. Wilcoxon Signed Rank tests showed a significant improvement in SI (p = 0.043) and CV (p = 0.043) upon recovery. On follow up, all five patients were well, with no further severe or atypical infections. CONCLUSIONS: DHR may be transiently abnormal during acute illness, and may therefore not be reliable when assessed during an acute illness. If these subjects had CGD, it would be of a hypomorphic variant that has not previously been described.

Oncogenic KRAS-induced epiregulin overexpression contributes to aggressive phenotype and is a promising therapeutic target in non-small-cell lung cancer.

KRAS mutations are one of the most common driver mutations in non-small-cell lung cancer (NSCLC) and finding druggable target molecules to inhibit oncogenic KRAS signaling is a significant challenge in NSCLC therapy. We recently identified epiregulin (EREG) as one of several putative transcriptional targets of oncogenic KRAS signaling in both KRAS-mutant NSCLC cells and immortalized bronchial epithelial cells expressing ectopic mutant KRAS. In the current study, we found that EREG is overexpressed in NSCLCs harboring KRAS, BRAF or EGFR mutations compared with NSCLCs with wild-type KRAS/BRAF/EGFR. Small interfering RNAs (siRNAs) targeting mutant KRAS, but not an siRNA targeting wild-type KRAS, significantly reduced EREG expression in KRAS-mutant and EREG-overexpressing NSCLC cell lines. In these cell lines, EREG expression was downregulated by MEK and ERK inhibitors. Importantly, EREG expression significantly correlated with KRAS expression or KRAS copy number in KRAS-mutant NSCLC cell lines. Further expression analysis using 89 NSCLC specimens showed that EREG was predominantly expressed in NSCLCs with pleural involvement, lymphatic permeation or vascular invasion and in KRAS-mutant adenocarcinomas. In addition, multivariate analysis revealed that EREG expression is an independent prognostic marker and EREG overexpression in combination with KRAS mutations was associated with an unfavorable prognosis for lung adenocarcinoma patients. In KRAS-mutant and EREG overexpressing NSCLC cells, siRNA-mediated EREG silencing inhibited anchorage-dependent and -independent growth and induced apoptosis. Our findings suggest that oncogenic KRAS-induced EREG overexpression contributes to an aggressive phenotype and could be a promising therapeutic target in oncogenic KRAS-driven NSCLC.

Comparison of cell proliferation and epigenetic modification of gene expression patterns in canine foetal fibroblasts and adipose tissue-derived mesenchymal stem cells.

OBJECTIVES: This study compared rate of cell proliferation, viability, cell size, expression patterns of genes related to pluripotency and epigenetic modification between canine foetal fibroblasts (cFF) and canine adipose tissue-derived mesenchymal stem cells (cAd-MSC). MATERIALS AND METHODS: Proliferation pattern, cell viability as well as cell size at each passage of cFF and cAd-MSC were measured when cultures reached confluence. In addition, real-time PCR was performed to investigate expression of Dnmt1, HDAC1, OCT4, SOX2, BAX, BCL2 genes with reference to ß-actin gene expression as an endogenous control in both cell lines. RESULTS: cFF and cAd-MSC differed in number of generations, but not in doubling times, at all passages. Mean cell size of cAd-MSC was significantly smaller than that of cFF. Cell viability was significantly lower in cFFs and apoptotic level was significantly lower in cAd-MSC compared to passage-matched cFF. In the expression of genes related to pluripotency and epigenetic modification, level of HDAC1 in cAd-MSC was significantly higher than in cFF, but expression of Dnmt1 did not differ between the two groups. OCT4 and SOX2 were significantly more highly expressed in cAd-MSC compared to cFF. CONCLUSIONS: cAd-MSC have higher stem-cell potential than cFF in terms of proliferation patterns, epigenetic modification and pluripotency, thus cAd-MSC could be more appropriate than cFF as donors of nuclei in somatic cell nuclear transfer for transgenesis.

Intracellular lipid accumulation inhibitory effect of Weissella koreensis OK1-6 isolated from Kimchi on differentiating adipocyte.

AIMS: To investigate the intracellular lipid accumulation inhibitory effect of spent culture medium extract and the cytoplasmic fraction of Weissella koreensis OK1-6 cells isolated from kimchi in differentiating 3T3-L1 cells. METHODS AND RESULTS: Differentiating 3T3-L1 cells were treated with either cytoplasmic fraction of W. koreensis OK1-6 cells or its spent media for 4 days. Both the spent culture medium extract and cytoplasmic fraction of W. koreensis OK1-6 cells significantly decreased the triglyceride concentration and intracellular lipid accumulation in the treated groups compared with the control group. The mRNA expression levels of C/EBP-α, one of the major transcriptional factors involved in adipocyte differentiation, were significantly less expressed in 3T3-L1 cells treated with the spent medium and cytoplasmic fraction. The expressions of aP2, fatty acid synthase (FAS) and SREBP1 genes were also decreased significantly. CONCLUSIONS: These results suggested that W. koreensis OK1-6 could play a crucial role in preventing intracellular lipid accumulation by down-regulating the expression of adipocyte-specific genes C/EBPα, aP2, SREBP1 and FAS. SIGNIFICANCE AND IMPACT OF THE STUDY: These results may contribute to nutraceutical and food industries in developing probiotic-based therapies for the treatment and prevention of obesity.

Long-term results of patients with malignant carcinoid syndrome receiving octreotide LAR.

BACKGROUND: Octreotide LAR is an established treatment for malignant carcinoid syndrome. However, studies with large number of patients and long follow-up are lacking. AIM: To present long-terms results with octreotide LAR, assessing duration of clinical and objective response and treatment tolerance, in a large, homogeneous cohort of patients with malignant carcinoid syndrome. METHODS: A total of 108 patients with metastatic midgut neuroendocrine tumours were included in this 8-year study. Clinical evaluation was based on a symptom score. Radiological assessment was based on RECIST (Response Evaluation Criteria In Solid Tumours) criteria. RESULTS: Of the 108 patients, 24% had a sustained symptomatic response. In the remaining patients, loss of symptomatic response with the initial dose was noted within 3-60 months. In 17% of them, symptoms were controlled by just an increase of octreotide LAR dose, whilst the other patients required additional treatment. Overall, in 45.3% of patients, symptoms were well controlled during the study period with only octreotide LAR, and no additional treatment was required. No significant adverse effects were noted. CONCLUSIONS: Octreotide LAR treatment provides a sustained symptomatic response in about half of the patients with malignant carcinoid syndrome and contributes to disease stabilization for a longer period than previously described.