Beyond the stomach: An updated view of Helicobacter pylori pathogenesis, diagnosis, and treatment

Helicobacter pylori(H. pylori) is an extremely common, yet underappreciated, pathogen that is able to alter host physiology and subvert the host immune response, allowing it to persist for the life of the host. H. pylori is the primary cause of peptic ulcers and gastric cancer. In the United States, the annual cost associated with peptic ulcer disease is estimated to be $6 billion and gastric cancer kills over 700000 people per year globally. The prevalence of H. pylori infection remains high(> 50%) in much of the world, although the infection rates are dropping in some developed nations. The drop in H. pylori prevalence could be a double-edged sword, reducing the incidence of gastric diseases while increasing the risk of allergies and esophageal diseases. The list of diseases potentially caused by H. pylori continues to grow; however, mechanistic explanations of how H. pylori could contribute to extragastric diseases lag far behind clinical studies. A number of host factors and H. pylori virulence factors act in concert to determine which individuals are at the highest risk of disease. These include bacterial cytotoxins and polymorphisms in host genes responsible for directing the immune response. This review discusses the latest advances in H. pylori pathogenesis, diagnosis, and treatment. Up-todate information on correlations between H. pylori and extragastric diseases is also provided.

Genomic analysis of epithelial ovarian cancer

卵巢的癌症是为在美国的女人的一个主要健康问题。尽管有可观的异质的证据，卵巢的癌症的大多数诉讼以一种类似的方式被对待。这些肿瘤的 clinicopathologic 特征的分子的基础仍然保持糟糕定义。整个染色体表示介绍是一个 genomic 工具，它能识别 dysregulated 基因并且揭开肿瘤的唯一的子类。到卵巢的癌症的这种技术的申请在卵巢的肿瘤的组织学和等级为差别提供了一个稳固的分子的基础。差别表示了基因识别小径在细胞增殖，侵略，活动性， chromosomal 不稳定性，和基因含有 silencing 和提供的新卓见进起源和这些癌症的潜在的治疗。全球基因表示介绍提供的增加的知识应该允许卵巢的癌症的更合理的治疗。这些技术从实验治疗正在导致范例移动到一条个别地定制的途径。这评论在它将在我们这疾病的理解和治疗上有的不同组织学和等级和影响的上皮的卵巢的癌症上总结新 genomic 数据。

Approximate Solutions to the Discontinuous Riemann-Hilbert Problem of Elliptic Systems of First Order Complex Equations

Several approximate methods have been used to find approximate solutions of elliptic systems of first order equations. One common method is the Newton imbedding approach, i.e. the parameter extension method. In this article, we discuss approximate solutions to discontinuous Riemann-Hilbert boundary value problems, which have various applications in mechanics and physics. We first formulate the discontinuous Riemann-Hilbert problem for elliptic systems of first order complex equations in multiply connected domains and its modified well-posedness, then use the parameter extensional method to find approximate solutions to the modified boundary value problem for elliptic complex systems of first order equations, and then provide the error estimate of approximate solutions for the discontinuous boundary value problem.

The Mechanism of Henipavirus Fusion:Examining the Relationships between the Attachment and Fusion Glycoproteins

The henipaviruses,represented by Nipah virus and Hendra virus,are emerging zoonotic viral pathogens responsible for repeated outbreaks associated with high morbidity and mortality in Australia,Southeast Asia,India and Bangladesh. These viruses enter host cells via a class I viral fusion mechanism mediated by their attachment and fusion envelope glycoproteins;efficient membrane fusion requires both these glycoproteins in conjunction with specific virus receptors present on susceptible host cells. The henipavirus attachment glycoprotein interacts with a cellular B class ephrin protein receptor triggering conformational alterations leading to the activation of the viral fusion(F) glycoprotein. The analysis of monoclonal antibody(mAb) reactivity with G has revealed measurable alterations in the antigenic structure of the glycoprotein following its binding interaction with receptor. These observations only appear to occur with full-length native G glycoprotein,which is a tetrameric oligomer,and not with soluble forms of G(sG) ,which are disulfide-linked dimers. Single amino acid mutations in a heptad repeat-like structure within the stalk domain of G can disrupt its association with F and subsequent membrane fusion promotion activity. Notably,these mutants of G also appear to confer a post-receptor bound conformation implicating the stalk domain as an important element in the G glycoprotein's structure and functional relationship with F. Together,these observations suggest fusion is dependent on a specific interaction between the F and G glycoproteins of the henipaviruses. Further,receptor binding induces measurable changes in the G glycoprotein that appear to be greatest in respect to the interactions between the pairs of dimers comprising its native tetrameric structure. These receptor-induced conformational changes may be associated with the G glycoprotein's promotion of the fusion activity of F.

Effects of delayed estrogen treatment and 20-HETE synthesis inhibition on postischemic pial artery response to acetylcholine in rats

Relatively little is known about the effects of estrogen on postischemic cerebral vasomotor dynamics after ischemic injury. Emerging hypotheses suggest that the timing after menopause at which hormone replacement is initiated might be important and might modulate the potential benefits of estrogen on brain rescue once a cerebral ischemic event occurs. Therefore, we sought to determine if protracted hypoestrogenicity modifies estrogen’s protective effects on postischemic pial artery dilatory dysfunction and if the arachidonic acid metabolite 20-hydroxyeicosatetraeonic (20-HETE) contributes to the dysfunction. Pial artery dilation to acetylcholine was examined before and 1 hour after 15 minutes forebrain ischemia. The rat study groups included: sexually mature males (M), naive (N), OVX (OV), estrogen-treated OVX females (E1;estrogen started 1 week post ovariectomy) and delayed estrogen-treated (E10;started 10 weeks post ovariectomy) females. Postischemic responses were assessed before and after superfusion of the 20-HETE synthesis inhibitor N-hydroxy-N’-(4-butyl-2-methylphenyl)-formamidine (HET0016). Postischemic acetylcholine dilation was depressed in M, OV and E10 compared to N and E1 rats. Compared to E1, delayed estrogen replacement worsened acetylcholine-induced dilation. Postischemic microvascular estrogen receptor alpha (ERα) density was similar in the OV, E1 and E10 rats. Postischemic application of HET0016 failed to improve acetylcholine dilation. Continuous infusion of HET0016 during and after ischemia did not reverse postischemic pial vasodilatory dysfunction. Timing of estrogen replacement may be critical for vascular health after cerebral ischemic injury. Postischemic loss of acetylcholine reactivity does not appear to involve mechanisms related to 20-HETE synthesis or microvascular ERα expression.

Perioperative Outcomes Following Surgical Treatment of the Neuromuscular Hip: An Analysis of the National Surgical Quality Improvement Program—Pediatrics

Background: Surgical treatment for neuromuscular (NM) hip subluxation or dislocation is undertaken to maintain functionality and decrease pain. Longterm complications are well described;however, the acute complication profile is poorly understood. Questions/Purpose: The aim of this study was to identify the rate of and risk factors for complications following surgical treatment of hip subluxation/dislocation, especially as it relate to NM children. Methods: Hip reconstruction cases in patients with a NM diagnosis and non-NM patients were obtained from the 2015 American College of Surgeons NSQIP-Pediatric database by CPT code. 30-day postoperative complications were classified according to the Clavien-Dindo system as minor (grade 1 or 2) or major (grade 3+). Patient and surgical factors were assessed in univariate and multivariate logistic regression analyses for association with post-operative complications. Results: 1081 cases were identified (median age 7.7, 55% female), of whom 420 (39%) had a NM diagnosis. Overall complication rate was significantly higher in NM patients (33% vs. 19%, p < 0.001). Numerous factors were associated with postoperative complication on univariate analysis. Multivariate analysis identified NM diagnosis (OR 1.5), age > 6 years (OR 1.5), or pelvic osteotomy (OR 1.9) as independent risk factors for complication. Conclusion: In pediatric reconstructive hip surgery requiring pelvic osteotomy, a NM diagnosis is associated with an increased risk of 30-day postoperative complications. Older age and increasing surgical complexity were also independently associated with complications. These findings support special attention for the older patients undergoing concomitant pelvic osteotomies to minimize complication rate.

Heterogeneously elevated branched-chain/aromatic amino acids among new-onset type-2 diabetes mellitus patients are potentially skewed diabetes predictors

BACKGROUND The lack of specific predictors for type-2 diabetes mellitus(T2DM)severely impacts early intervention/prevention efforts.Elevated branched-chain amino acids(BCAAs:Isoleucine,leucine,valine)and aromatic amino acids(AAAs:Tyrosine,tryptophan,phenylalanine)show high sensitivity and specificity in predicting diabetes in animals and predict T2DM 10-19 years before T2DM onset in clinical studies.However,improvement is needed to support its clinical utility.AIM To evaluate the effects of body mass index(BMI)and sex on BCAAs/AAAs in new-onset T2DM individuals with varying body weight.METHODS Ninety-seven new-onset T2DM patients(<12 mo)differing in BMI[normal weight(NW),n=33,BMI=22.23±1.60;overweight,n=42,BMI=25.9±1.07;obesity(OB),n=22,BMI=31.23±2.31]from the First People’s Hospital of Yunnan Province,Kunming,China,were studied.One-way and 2-way ANOVAs were conducted to determine the effects of BMI and sex on BCAAs/AAAs.RESULTS Fasting serum AAAs,BCAAs,glutamate,and alanine were greater and high-density lipoprotein(HDL)was lower(P<0.05,each)in OB-T2DM patients than in NW-T2DM patients,especially in male OB-T2DM patients.Arginine,histidine,leucine,methionine,and lysine were greater in male patients than in female patients.Moreover,histidine,alanine,glutamate,lysine,valine,methionine,leucine,isoleucine,tyrosine,phenylalanine,and tryptophan were significantly correlated with abdominal adiposity,body weight and BMI,whereas isoleucine,leucine and phenylalanine were negatively correlated with HDL.CONCLUSION Heterogeneously elevated amino acids,especially BCAAs/AAAs,across new-onset T2DM patients in differing BMI categories revealed a potentially skewed prediction of T2DM development.The higher BCAA/AAA levels in obese T2DM patients would support T2DM prediction in obese individuals,whereas the lower levels of BCAAs/AAAs in NW-T2DM individuals may underestimate T2DM risk in NW individuals.This potentially skewed T2DM prediction should be considered when BCAAs/AAAs are to be used as the T2DM predictor.

Polymorphism in the interleukin-17A promoter contributes to gastric cancer

AIM:To evaluate the contribution of the G-197A polymorphism in the interleukin-17(IL-17)promoter region to gastric cancer risk in an Iranian population.METHODS:We performed a case control study using samples from 161 individuals with gastric cancer and171 healthy controls.For each individual,the G-197A genotype was determined by restriction fragment length polymorphism analysis of polymerase chain reaction-amplified fragments.Statistical analyses were performed to determine whether any demographic or behavioral factors,infection with Helicobacter pylori(H.pylori),or a particular G-197A genotype was associated with gastric cancer risk.RESULTS:We found that the G-197A genotype wassignificantly associated with increased gastric cancer risk(P=0.001).Patients who were homozygous(AA)at position-197 were 2.9 times more likely to develop disease(95%CI:1.56-5.4;P=0.001).Furthermore,logistic regression analysis revealed that the presence of a single A allele increased the risk of gastric cancer up to 1.7-fold(95%CI:1.26-2.369;P=0.001).This association was observed for early stage gastric adenocarcinomas only,and was not linked to H.pylori infection.CONCLUSION:These results suggest that carrying one or more G-197A polymorphisms at position-197 in the IL-17 promoter region significantly increases gastric cancer risk in this patient population.

Inducible nitric oxide synthetase genotype and Helicobacter pylori infection affect gastric cancer risk

AIM:To investigate the association of the inducible nitric oxide synthetase(iNOS) C150T polymorphism with Helicobacter pylori(H.pylori) infection and gastric cancer(GC) risk in Iran.METHODS:In order to determine whether there was a correlation between iNOS genotype and GC in Iran,we conducted a case-control study using samples from 329 individuals.For each sample,the C150T iNOS polymorphism was genotyped by polymerase chain reaction(PCR) and restriction digestion.Patients were grouped by cancer presence,demographic and behavior characteristics,and H.pylori infection status.Statistical tests were conducted to determine whether any behavioral factors or a particular iNOS genotype was associated with GC in the study population.RESULTS:In this population,we found that smoking,hot beverage consumption,a familial history of GC and H.pylori infection status were significantly associated with GC development(P = 0.015,P < 0.001,P = 0.0034,and P < 0.015,respectively).The distribution of the C150T iNOS genotypes among the two study groups was not statistically significant alone,but was impacted by H.pylori infection status.When compared to the non-H.pylori infected group,cancer patients who had a heterozygous CT genotype and were also infected with H.pylori were 2.1 times more at risk of developing GC [odds ratio(OR) = 2.1,P = 0.03] while those with a homozygous TT genotype and infected with H.pylori were 5.0 times more at risk of developing GC(OR = 5.0,P = 0.029).In contrast,this association was not seen in patients in the control group.CONCLUSION:A CT or TT polymorphism at position 150 in the iNOS gene significantly increases the risk of GC and may be a marker for GC susceptibility.

Quantitative analysis of a panel of gene expression in prostate cancer——with emphasis on NPY expression analysis

Objective: To investigate molecular alterations associating with prostate carcinoma progression and potentially provide information toward more accurate prognosis/diagnosis. Methods: A set of laser captured microdissected (LCM) speci- mens from 300 prostate cancer (PCa) patients undergoing radical prostatectomy (RP) were defined. Ten patients representing "aggressive" PCa, and 10 representing "non-aggressive" PCa were selected based on prostate-specific antigen (PSA) recurrence, Gleason score, pathological stage and tumor cell differentiation, with matched patient age and race between the two groups. Normal and neoplastic prostate epithelial cells were collected with LCM from frozen tissue slides obtained from the RP specimens. The expressions of a panel of genes, including NPY, PTEN, AR, AMACR, DD3, and GSTP1, were measured by quantitative real-time RT-PCR (TaqMan), and correlation was analyzed with clinicopathological features. Results: The expressions of AMACR and DD3 were consistently up-regulated in cancer cells compared to benign prostate epithelial cells in all PCa patients, whereas GSTP1 expression was down regulated in each patient. NPY, PTEN and AR exhibited a striking difference in their expression patterns between aggressive and non-aggressive PCas (P=0.0203, 0.0284, and 0.0378, respectively, Wilcoxon rank sum test). The lower expression of NPY showed association with "aggressive" PCas based on a larger PCa patient cohort analysis (P=0.0037, univariate generalized linear model (GLM) analysis). Conclusion: Despite widely noted heterogeneous nature of PCa, gene ex- pression alterations of AMACR, DD3, and GSTP1 in LCM-derived PCa epithelial cells suggest for common underlying mecha- nisms in the initiation of PCa. Lower NPY expression level is significantly associated with more aggressive clinical behavior of PCa; PTEN and AR may have potential in defining PCa with aggressive clinical behavior. Studies along these lines have potential to define PCa-associated gene expression alterations and likely co-regulation of genes/pathways critical in the biology of PCa onset/progression.

Chronotype and self-reported sleep,alertness,and mental health in U.S. sailors

Service members are at risk for sleep and psychological conditions affecting their readiness. Chronotype(“morningness”or “eveningness”) is strongly associated with sleep, health and performance. The objective of this study was to examine associations between validated measures of chronotype and sleep quality, daytime functioning, alertness,and symptoms of depression, anxiety, and post-traumatic stress disorder(PTSD) in US service members(n=298).Although predominantly young males(who skew toward eveningness in civilian populations), these Sailors skewed toward morningness(35.6% morning, 51.3% intermediate). Eveningness was associated with symptoms of depression and PTSD(P<0.01), less time in bed(P<0.05), more sleep disruption(P<0.01), and poorer daytime functioning and alertness(P<0.05). Evening types were less likely to consider sleep important for performance(P<0.05). To maximize service member readiness, schedules should be aligned with endogenous rhythms, whenever possible, and evening chronotypes may benefit from targeted interventions. Chronotype should be examined alongside health and readiness in service members.

Boundary Value Problems for Nonlinear Elliptic Equations of Second Order in High Dimensional Domains

This paper mainly concerns oblique derivative problems for nonlinear nondivergent elliptic equations of second order with measurable coefficients in a multiply connected domain. Under certain condition, we derive a priori estimates of solutions. By using these estimates and the fixed-point theorem, we prove the existence of solutions.

A 30% incidence of renal cysts with varying sizes and densities in biomedical research swine is not associated with renal dysfunction

Background:Renal cystic disease arising from various etiologies results in fluid-filled cavities within the kidneys.Moreover,preexisting renal dysfunction has been shown to exacerbate multiple pathologies.While swine bred for biomedical research are often clinically inspected for illness/parasites,more advanced diagnostics may aid in uncovering underlying renal abnormalities.Methods:Computed tomography was performed in 54 female prepubertal Yorkshire swine to characterize renal cysts;urine and blood chemistry,and histology of cysts were also performed.Results:Digital reconstruction of right and left kidneys demonstrated that roughly one-third of the animals(17/54;31%)had one or more renal cyst.Circulating biomarkers of renal function were not different between animals that had cysts and those that did not.Alternatively,urinary glucose(P=.03)was higher and sodium(P=.07)tended to be lower in animals with cysts compared to animals without,with no differences in protein(P=.14)or potassium(P=.20).Aspiration of cystic fluid was feasible in two animals,which revealed that the cystic fluid urea nitrogen(97.6±28.7 vs 911.3±468.2 mg/dL),potassium(29.8±14.4 vs 148.2±24.85 mmol/L),uric acid(2.55±1.35 vs 11.4±5.65 mg/dL),and creatinine(60.34±17.26 vs 268.99±95.79 mg/dL)were much lower than in the urine.Histology demonstrated a cyst that markedly compresses the adjacent cortex and is lined by a single layer of flattened epithelium,bounded by fibrous connective tissue which extends into the parenchyma.There is tubular atrophy and loss in these areas.Conclusion:This study provides valuable insight for future studies focusing on kidney function in swine bred for biomedical research.

First imported Plasmodium ovale malaria in Central America: Case report of a Guatemalan soldier and a call to improve its accurate diagnosis

The Mesoamerican Ministers of Health have set 2020 as the target for malaria elimination to be achieved in the region. Imported malaria cases are a potential threat to countries attempting elimination or working to prevent resurgence. We report the first imported Plasmodium ovale infection with molecular confirmation in Central America, which occurred in a Guatemalan soldier that had been deployed in Africa. The obstacles for its diagnosis using the standard microscopy technique and the need to improve its detection are discussed.

Comparison of protein concentrations in serum versus plasma from Alzheimer’s patients

Background: There is great interest in developing blood-based biomarkers for Alzheimer’s disease (AD);however, there is no consensus as to what blood fraction is most appropriate for analyzing particular markers. The current study provides empirical evidence regarding how blood-based proteins vary depending on whether they are assayed in serum or plasma. Methods: Weanalyzed concentrations of 100 proteins in matched samples of serum and plasma from 39 Caucasian AD participants from the Texas Alzheimer’s Research and Care Consortium bymultiplex immunoassay. Results: Concentrations of 40 proteins were highly correlated (r2≥ 0.75) between plasma and serum while the remaining proteins were moderately to weakly correlated (r2< 0.75). Discussion: Whether plasma vs. serum is assayed can have a large impact on the observed concentration of some proteins, including several proteins that are of great interest to AD pathophysiology. The current findings may explain the significant discrepancies often times reported in the AD biomarker field.

Highlights from the prostate cancer genome report

Prostate cancer （CAP） is the second most frequently diagnosed cancer of men worldwide （899 000 new cases, 13.6% of the total）, with nearly 75% of the registered cases occurring in developed countries （644 000 cases）.1 Blood prostate-specific antigen test has revolutionized the early detection of CaP and organ-confined CaP is effectively managed by state-of-the-art treatments including radical prostatectomy or radiation therapy.2 In the past decade, tremendous progress has also been made in our understanding of the biology and common genomic alterations in CaP.3＇4 New molecular marker assays have promise in improving CaP diagnosis.5-8 Despite these advances, major challenges remain with our ability to distinguish indolent cancers from the more aggressive cancers detected early due to widely used prostate-specific antigen test. Furthermore, development of molecular stratification of CaP for targeted and more effective therapies is critically needed.

Factors and expectations influencing concussion disclosure within NCAA DivisionⅠathletes:A mixed methodological approach

Background:Participation in sports is associated with many benefits to all aspects of health;however,it also comes with the risk of injury,particularly concussions.Self-disclosure and care seeking following a concussion are especially important because of the lack of outwardly visible signs and/or symptoms.Although recent research has explored factors affecting concussion disclosure,use of isolated methodologies limits the ability to contextualize how disclosure or nondisclosure occurs.Therefore,the purpose of this study was to describe the factors and expectations of National Collegiate Athletic Association(NCAA)athletes that may influence concussion disclosure.Methods:This mixed-methods convergent parallel research study included 25 NCAA Division I athletes representing 13 sports,all of whom completed a concussion-education session with pre-/post-test surveys and a semistructured interview.Eligible athletes were at least 18 years old and on an NCAA roster.The surveys focused on previous concussion-related disclosure behaviors,knowledge,attitudes,beliefs,norms,and intentions about disclosing concussion.Interviews focused on the athletes’experiences related to concussion disclosure.Survey data were analyzed using descriptive statistics and Mann-Whitney U tests.Interviews were analyzed using a Consensual Qualitative Research tradition.Results:Participants had good concussion knowledge(median=46.0),positive attitudes(median=38.0),strong beliefs(median=13.0),and strong intentions to disclose concussion symptoms(median=7.0).None of the constructs differed by participants’gender.Although quantitative findings were mostly positive,interview data highlighted factors that may explain why some participants are successful in disclosing concussions and why others may find disclosure difficult.Educational efforts,sport culture,and medical professional presence were the primary facilitators discussed by participants.Stigma,pressure,and a lack of team support were perceived as disclosure barriers.Conclusion:The context in which concussion disclosure occurs or does not occur is vital to the success of educational interventions.Interventions must prioritize stakeholder-and team-based perspectives on concussion to establish a network supportive to disclosure.

Post-traumatic stress disorder risk and brain-derived neurotrophic factor Val66Met

Brain-derived neurotrophic factor(BDNF), which regulates neuronal survival, growth differentiation, and synapse formation, is known to be associated with depression and post-traumatic stress disorder(PTSD). However, the molecular mechanism for those mental disorders remains unknown. Studies have shown that BDNF is associated with PTSD risk and exaggerated startle reaction(a major arousal manifestation of PTSD) in United States military service members who were deployed during the wars in Iraq and Afghanistan. The frequency of the Met/Met in BDNF gene was greater among those with PTSD than those without PTSD. Among individuals who experienced fewer lifetime stressful events, the Met carriers have significantly higher total and startle scores on the PTSD Checklist than the Val/Val carriers. In addition, subjects with PTSD showed higher levels of BDNF in their peripheral blood plasma than the non-probable-PTSD controls. Increased BDNF levels and startle response were observed in both blood plasma and brain hippocampus by inescapable tail shock in rats. In this paper, we reviewed these data to discuss BDNF as a potential biomarker for PTSD risk and its possible roles in the onset of PTSD.