State of the art in research on the gut-liver and gut-brain axis in poultry

The relationship between the intestines and their microbiota,the liver,and the neuronal system is called the gutliver-brain axis.This relationship has been studied and observed for a relatively short time but is considered in the development of research focused on,e.g.,liver diseases and intestinal dysbiosis.The role of the gut microbiota in this relationship is crucial,as it acts on poultry’s performance and feed utilization,affecting meat and egg quality.The correct composition of the intestinal microbiota makes it possible to determine the essential metabolic pathways and biological processes of the individual components of the microbiota,allowing further speculation of the role of microbial populations on internal organs such as the liver and brain in the organism.The gut microbiota forms a complex,dense axis with the autonomic and enteric nervous systems.The symbiotic relationship between the liver and gut microbiota is based on immune,metabolic and neuroendocrine regulation,and stabilization.On the other hand,the gut-brain axis is a bidirectional interaction and information transfer system between the gastrointestinal tract and the central nervous system.The following paper will discuss the current state of knowledge of the gut-liver-brain axis of poultry,including factors that may affect this complex relationship.

Solid-phase microextraction of endogenous metabolites from intact tissue validated using a Biocrates standard reference method kit

Improved analytical methods for the metabolomic profiling of tissue samples are constantly needed.Currently,conventional sample preparation methods often involve tissue biopsy and/or homogenization,which disrupts the endogenous metabolome.In this study,solid-phase microextraction(SPME)fibers were used to monitor changes in endogenous compounds in homogenized and intact ovine lung tissue.Following SPME,a Biocrates AbsoluteIDQ assay was applied to make a downstream targeted metabolomics analysis and confirm the advantages of in vivo SPME metabolomics.The AbsoluteIDQ kit enabled the targeted analysis of over 100 metabolites via solid-liquid extraction and SPME.Statistical analysis revealed significant differences between conventional liquid extractions from homogenized tissue and SPME results for both homogenized and intact tissue samples.In addition,principal component analysis revealed separated clustering among all the three sample groups,indicating changes in the metabolome due to tissue homogenization and the chosen sample preparation method.Furthermore,clear differences in free metabolites were observed when extractions were performed on the intact and homogenized tissue using identical SPME procedures.Specifically,a direct comparison showed that 47 statistically distinct metabolites were detected between the homogenized and intact lung tissue samples(P<0.05)using mixed-mode SPME fibers.These changes were probably due to the disruptive homogenization of the tissue.This study's findings highlight both the importance of sample preparation in tissue-based metabolomics studies and SPME's unique ability to perform minimally invasive extractions without tissue biopsy or homogenization while providing broad metabolite coverage.

辊弯成形下塑性应变对挤压态6063T66铝合金型材疲劳性能的影响

分析从辊弯成形型材区和预应变材料取样的材料的拉伸塑性应变。利用概率Weibull累积分布(P-S-N曲线)近似高周疲劳的实验数据。利用LS-Dyna程序和实验数据对辊弯成形进行数值模拟,建立疲劳寿命预测模型。材料的循环行为表明,随着静态失效水平的增加,疲劳寿命分布减小。断裂表面的断口形貌分析表明,由于晶界附近的位错积累,拉伸预应变的晶间裂纹水平增加。所提模型预测结果与概率散射带具有良好的相关性(误差低于10%)。

In vivo solid phase microextraction for therapeutic monitoring and pharmacometabolomic fingerprinting of lung during in vivo lung perfusion of FOLFOX

In vivo lung perfusion(IVLP)is a novel isolated lung technique developed to enable the local,in situ administration of high-dose chemotherapy to treat metastatic lung cancer.Combination therapy using folinic acid(FOL),5-fluorouracil(F),and oxaliplatin(OX)(FOLFOX)is routinely employed to treat several types of solid tumours in various tissues.However,F is characterized by large interpatient variability with respect to plasma concentration,which necessitates close monitoring during treatments using of this compound.Since plasma drug concentrations often do not reflect tissue drug concentrations,it is essential to utilize sample-preparation methods specifically suited to monitoring drug levels in target organs.In this work,in vivo solid-phase microextraction(in vivo SPME)is proposed as an effective tool for quantitative therapeutic drug monitoring of FOLFOX in porcine lungs during pre-clinical IVLP and intravenous(IV)trials.The concomitant extraction of other endogenous and exogenous small molecules from the lung and their detection via liquid chromatography coupled to high resolution mass spectrometry(LC-HRMS)enabled an assessment of FOLFOX's impact on the metabolomic profile of the lung and revealed the metabolic pathways associated with the route of administration(IVLP vs.IV)and the therapy itself.This study also shows that the immediate instrumental analysis of metabolomic samples is ideal,as long-term storage at80℃ results in changes in the metabolite content in the sample extracts.

Cartilage Wear in Healthy and Osteoarthritis Joints

This study is designed to determine whether the outermost layer of articular cartilage is deficient in Osteoarthritis (OA). Phospholipids present in healthy and osteoarthritis (OA) synovial fluid show significant differences in their concentration. While examining the surface properties of OA joints, we found that OA PLs molecules cannot support lubrication, and increased friction was observed. Our lubrication mechanism was based on a surface active phospholipids (SAPL) multibilayer which in OA condition was deactivated and removed from the cartilage surface under OA conditions. Cartilage wettability study clearly demonstrated a significant decrease in hydrophobicity, the contact angle, θ (theta), dropping from 103° from bovine healthy cartilage to 65° in surface partially depleted and 35.1° for completely depleted surface. These results are discussed in the context that surface active phospholipid (SAPL) and lubricin, each has specific roles in a lamellar-repulsive lubrication system. However, deactivated phospholipid molecules are major indicator of cartilage wear (model) introduced in this study.

Changes in characteristics of patients with hepatitis C virus-related cirrhosis from the beginning of the interferon-free era

BACKGROUND Nearly 290000 patients with chronic hepatitis C die annually from the most severe complications of the disease.One of them is liver cirrhosis,which occurs in about 20%of patients chronically infected with the hepatitis C virus(HCV).Direct-acting antivirals(DAAs),which replaced interferon(IFN)-based regimens,significantly improved the prognosis of this group of patients,increasing HCV eradication rates and tolerability of therapy.Our study is the first to assess changes in patient profile,effectiveness,and safety in the HCV-infected cirrhotic population in the IFN-free era.AIM To document changes in patient characteristics and treatment regimens along with their effectiveness and safety profile over the years.METHODS The studied patients were selected from 14801 chronically HCV-infected individuals who started IFN-free therapy between July 2015 and December 2021 in 22 Polish hepatology centers.The retrospective analysis was conducted in real-world clinical practice based on the EpiTer-2 multicenter database.The measure of treatment effectiveness was the percentage of sustained virologic response(SVR)calculated after excluding patients lost to follow-up.Safety data collected during therapy and the 12-wk post-treatment period included information on adverse events,including serious ones,deaths,and treatment course.RESULTS The studied population(n=3577)was balanced in terms of gender in 2015-2017,while the following years showed the dominance of men.The decline in the median age from 63 in 2015-2016 to 61 years in 2021 was accompanied by a decrease in the percentage of patients with comorbidities and comedications.Treatment-experienced patients dominated in 2015-2016,while treatment-naive individuals gained an advantage in 2017 and reached 93.2%in 2021.Genotype(GT)-specific options were more prevalent in treatment in 2015-2018 and were supplanted by pangenotypic combinations in subsequent years.The effectiveness of the therapy was comparable regardless of the period analyzed,and patients achieved an overall response rate of 95%,with an SVR range of 72.9%-100%for the different therapeutic regimens.Male gender,GT3 infection,and prior treatment failure were identified as independent negative predictors of therapeutic success.CONCLUSION We have documented changes in the profile of HCV-infected cirrhotic patients over the years of accessibility to changing DAA regimens,confirming the high effectiveness of IFN-free therapy in all analyzed periods.

Real-world effectiveness and safety of direct-acting antivirals in hepatitis C virus patients with mental disorders

BACKGROUND It is estimated that 58 million people worldwide are infected with the hepatitis C virus(HCV).Patients with severe psychiatric disorders could not be treated with previously available interferon-based therapies due to their unfavorable side effect profile.This has changed with the introduction of direct-acting antivirals(DAA),although their real-life tolerance and effectiveness in patients with different psychiatric disorders remain to be demonstrated.AIM To evaluate the effectiveness and safety of DAA in patients with various mental illnesses.METHODS This was a retrospective observational study encompassing 14272 patients treated with DAA for chronic hepatitis C in 22 Polish hepatology centers,including 942 individuals diagnosed with a mental disorder(anxiety disorder,bipolar affective disorder,depression,anxiety-depressive disorder,personality disorder,schizophrenia,sleep disorder,substance abuse disorder,and mental illness without a specific diagnosis).The safety and effectiveness of DAA in this group were compared to those in a group without psychiatric illness(n=13330).Antiviral therapy was considered successful if serum ribonucleic acid(RNA)of HCV was undetectable 12 wk after its completion[sustained virologic response(SVR)].Safety data,including the incidence of adverse events(AEs),serious AEs(SAEs),and deaths,and the frequency of treatment modification and discontinuation,were collected during therapy and up to 12 wk after treatment completion.The entire study population was included in the intent-to-treat(ITT)analysis.Per-protocol(PP)analysis concerned patients who underwent HCV RNA evaluation 12 wk after completing treatment.RESULTS Among patients with mental illness,there was a significantly higher percentage of men,treatmentnaive patients,obese,human immunodeficiency virus and hepatitis B virus-coinfected,patients with cirrhosis,and those infected with genotype 3(GT3)while infection with GT1b was more frequent in the population without psychiatric disorders.The cure rate calculated PP was not significantly different in the two groups analyzed,with a SVR of 96.9% and 97.7%,respectively.Although patients with bipolar disorder achieved a significantly lower SVR,the multivariate analysis excluded it as an independent predictor of treatment non-response.Male sex,GT3 infection,cirrhosis,and failure of previous therapy were identified as independent negative predictors.The percentage of patients who completed the planned therapy did not differ between groups with and without mental disorders.In six patients,symptoms of mental illness(depression,schizophrenia)worsened,of which two discontinued treatments for this reason.New episodes of sleep disorders occurred significantly more often in patients with mental disorders.Patients with mental illness were more frequently lost to follow-up(4.2%vs 2.5%).CONCLUSION DAA treatment is safe and effective in HCV-infected patients with mental disorders.No specific psychiatric diagnosis lowered the chance of successful antiviral treatment.

高速永磁同步电机在多物理场和变流器约束下的设计

高速电机中多物理场是强耦合的,其影响是甚至相互矛盾的。因此,高速电机的设计受到多物理场的强制约。此外,变流器的电压和电流都受限,由此也制约了高速电机的设计。当电机功率较大时,所有这些约束变得更加显著,因此较难获得一个很好的优化设计方案。该文以一台350kW、13.5kr/min的大功率高速内置式永磁同步电机作为案例,阐述其设计方法与优化过程。针对不同工况,研究电机永磁磁链与绕组电感的匹配设计,以确保变流器的电压和电流限制均得到满足。之后,通过有限元的手段研究相关的电机设计要点,特别是考虑电磁特性、机械应力和动力学特性的转子拓扑结构;也通过计算流体动力学(CFD)手段研究电机的热性能。由此可实现完整的高速电机多物理场设计。

Brain-gut axis in the pathogenesis of Helicobacter pylori infection

Helicobacter pylori(H.pylori)infection is the main pathogenic factor for upper digestive tract organic diseases.In addition to direct cytotoxic and proinflammatory effects,H.pylori infection may also induce abnormalities indirectly by affecting the brain-gut axis,similar to other microorganisms present in the alimentary tract.The brain-gut axis integrates the central,peripheral,enteric and autonomic nervous systems,as well as the endocrine and immunological systems,with gastrointestinal functions and environmental stimuli,including gastric and intestinal microbiota.The bidirectional relationship between H.pylori infection and the brain-gut axis influences both the contagion process and the host’s neuroendocrine-immunological reaction to it,resulting in alterations in cognitive functions,food intake and appetite,immunological response,and modification of symptom sensitivity thresholds.Furthermore,disturbances in the upper and lower digestive tract permeability,motility and secretion can occur,mainly as a form of irritable bowel syndrome.Many of these abnormalities disappear following H.pylori eradication.H.pylori may have direct neurotoxic effects that lead to alteration of the brain-gut axis through the activation of neurogenic inflammatory processes,or by microelement deficiency secondary to functional and morphological changes in the digestive tract.In digestive tissue,H.pylori can alter signaling in the brain-gut axis by mast cells,the main brain-gut axis effector,as H.pylori infection is associated with decreased mast cell infiltration in the digestive tract.Nevertheless,unequivocal data concerning the direct and immediate effect of H.pylori infection on the brain-gut axis are still lacking.Therefore,further studies evaluating the clinical importance of these host-bacteria interactions will improve our understanding of H.pylori infection pathophysiology and suggest new therapeutic approaches.

Pressurized intraperitoneal aerosol chemotheprapy after misdiagnosed gastric cancer: case report and review of the literature

We report the first application of pressurized intraperitoneal aerosol chemotherapy(PIPAC) as a rescue therapy before palliative D2 gastrectomy combined with liver metastasectomy performed in a 49-yearold woman with peritoneal carcinomatosis who was primarily diagnosed with and underwent surgery for a Krukenberg tumor. The PIPAC procedure was performed with the use of cisplatin at 7.5 mg/m2 and doxorubicin at 1.5 mg/m2 for 30 min at 37 ℃. Eight weeks after the PIPAC procedure, the patient underwent open classic D2 gastrectomy with the creation of a Roux-en-Y anastomosis(RNY) combined with liver metastasectomy. The patient underwent the classic protocol for chemotherapy combined with Xeloda. The patient felt better and returned to her daily activities. Multicenter data should be gathered to confirm the usefulness of PIPAC as a rescue or neoadjuvant supportive therapy in a very select group of patients who have been recently qualified to undergo classic chemotherapy or standard oncologic surgical procedures.

Impact of IL28B and OAS gene family polymorphisms on interferon treatment response in Caucasian children chronically infected with hepatitis B virus

AIM To investigate the impact of IL28 B and OAS gene polymorphisms on interferon treatment responses in children with chronic hepatitis B.METHODS We enrolled 52 children(between the ages of 4 and 18) with hepatitis B e antigen-negative chronic hepatitis B(CHB), who were treated with pegylated interferon alfa for 48 wk. Single nucleotide polymorphisms in the OAS1(rs1131476), OAS2(rs1293747),OAS3(rs2072136), OASL(rs10849829) and IL28B(rs12979860, rs12980275 and rs8099917) genes were studied to examine their associations with responses to IFN treatment in paediatric patients. We adopted two criteria for the therapeutic response, achieving an hepatitis B virus(HBV) DNA level < 2000 IU/m L and normalization of ALT activity(< 40 IU/L). To perform the analyses, we compared the patients in terms of achieving a partial response(PR) and a complete response(CR) upon measurement at the 24-wk posttreatment follow-up. RESULTS The PR and CR rates were 80.8% and 42.3%, respectively. Factors such as age, gender and liver histology had no impact on the type of response(partial or complete). A statistically significant relationship between higher baseline HBV DNA and ALT activity levels and lower rates of PR and CR was shown(P < 0.05). The allele association analysis revealed that only the IL-28 B rs12979860(C vs T) and IL28 B rs12980275(A vs G) markers significantly affected the achievement of PR(P = 0.021, OR = 3.3, 95%CI: 1.2-9.2 and P = 0.014, OR = 3.7, 95%CI: 1.3-10.1, respectively). However, in the genotype analysis, only IL-28 B rs12980275 was significantly associated with PR(AA vs AG-GG, P = 0.014, OR = 10.9, 95%CI: 1.3-93.9). The association analysis for CR showed that the TT genotype of IL28 B rs12979860 was present only in the no-CR group(P = 0.033) and the AA genotype of OASL rs10849829 was significantly more frequent in the noCR group(P = 0.044, OR = 0.26, 95%CI: 0.07-0.88). The haplotype analysis revealed significant associations between PR and CR and OAS haplotype(P = 0.0002 and P = 0.001, respectively), but no association with IL28 B haplotype was observed.CONCLUSION IL28 B and OAS polymorphisms are associated with different clinical outcomes in CHB children treated with interferon.

Solid phase microextraction chemical biopsy tool for monitoring of doxorubicin residue during in vivo lung chemo-perfusion

Development of a novel in vivo lung perfusion(IVLP)procedure allows localized delivery of high-dose doxorubicin(DOX)for targeting residual micrometastatic disease in the lungs.However,DOX delivery via IVLP requires careful monitoring of drug level to ensure tissue concentrations of this agent remain in the therapeutic window.A small dimension nitinol wire coated with a sorbent of biocompatible morphology(Bio-SPME)has been clinically evaluated for in vivo lung tissue extraction and determination of DOX and its key metabolites.The in vivo Bio-SPME-IVLP experiments were performed on pig model over various(150 and 225 mg/m^(2))drug doses,and during human clinical trial.Two patients with metastatic osteosarcoma were treated with a single 5 and 7 μg/mL(respectively)dose of DOX during a 3-h IVLP.In both pig and human cases,DOX tissue levels presented similar trends during IVLP.Human lung tissue concentrations of drug ranged between 15 and 293 μg/g over the course of the IVLP procedure.In addition to DOX levels,Bio-SPME followed by liquid chromatography-mass spectrometry analysis generated 64 metabolic features during endogenous metabolite screening,providing information about lung status during drug administration.Real-time monitoring of DOX levels in the lungs can be performed effectively throughout the IVLP procedure by in vivo Bio-SPME chemical biopsy approach.Bio-SPME also extracted various endogenous molecules,thus providing a real-time snapshot of the physiology of the cells,which might assist in the tailoring of personalized treatment strategy.

The influence of in ovo injection with the prebiotic DiNovoon the development of histomorphological parameters of the duodenum, body mass and productivity in large-scale poultry production conditions

Background: Among various feed additives currently used in poultry nutrition, an important role is played by bioactive substances, including prebiotics. The beneficial effect of these bioactive substances on the gastrointestinal tract and immune system give rise to improvements in broiler health and performance nutrition, thus increasing the productivity of these birds. An innovative method for introducing bioactive substances into chickens is the in ovo injection into eggs intended for hatching. The aim of the study was to evaluate the development of histomorphological parameters of the duodenum and productivity in chickens injected in ovo with the prebiotic DiNovo~?(extract of Laminaria species of seaweed, BioA tlantis Ltd., Ireland) on d 12 of incubation, under large-scale, high density poultry production conditions.Results: There was no significant impact of the injection of DiNovo~? prebiotic on the production parameters of broiler chickens(body weight, FCR, EBI and mortality) obtained on d 42 of rearing. No significant impact of the DiNovo~? injection on the duodenum weight and length was observed, as wel as on the CSA, diameter and muscular layer thickness of the duodenum. The in ovo injection of DiNovo~? significantly increased the width of the duodenal vil i(P < 0.05) and crypt depth(P < 0.01) of chickens on d 21 of rearing. Other histomorphological parameters of duodenal vil i at d 42 of chickens rearing such as: the height, width, and cross section area of vil i were significantly greater in chickens from the control group compared to those from the DiNovo~? group(P < 0.05 and P < 0.01).Conclusions: In conclusion, this study demonstrates that injection of DiNovo~? prebiotic into the air chamber of egg significantly influences the histomorphological parameters on d 21 of rearing without negatively affecting productivity in chickens at the end of rearing.

Acute liver failure caused by concurrent autoimmune hepatitis and hepatitis B in a 16-year old girl

A 16 year-old girl was admitted to hospital because of fatigue and somnolence,nausea,epistaxis and jaund ice.Physical examination revealed jaundice,an enlarged liver and tenderness of upper right abdom en.Laboratory tests revealed an increased level of acute liver failure,bilirubin,bile acids,GGTP and a decreased prot hrombin ratio,with elevated gamma-globulin and IgG levels,and the presence of anti-mitochondrial M2 antibodies and HBV infection markers.The patient was diagnosed with liver failure resulting from chronic hepatitis B with an autoimmune component.The treatment consisted of steroids,azathioprine,vitam in K,low-protein diet and lactulose enemas.After undergoing a molecular test(HBV DNA 3.23 × 105 IU/mL and mutations 204 and 80),the treatment was mo tient was discharged in good clinical condition,with the recommendation of continued entecavir,prednisone and azathioprine.In subsequent months,no clinical deter ioration or abnormal biochemical liver function test results were found,despite the discontinuation of immunos up pressive therapy after 10 mo.The patient cont inues entecavir therapy.

What's new in hepatitis C virus infections in children?

The number of hepatitis C virus(HCV) infection cases is relatively low in children. This low number may be connected with the lack of screening tests and the asymptomatic course of infection. Currently,mother-toinfant transmission is the most common cause of HCV infection amongst children in developed countries. It is important to introduce routine screening tests for HCV in pregnant women. The risk of vertical transmission of HCV is estimated at approximately 5%(3%-10%). Currently,we do not have HCV transmission prevention methods. Some factors could potentially be eliminated by elective caesarean section. Currently,the method of prevention of perinatal HCV infection is the early identification and effective treatment of infections in young women in the preconception period. We describe genetic tests(IL-28 B single nucleotide polymorphisms) to identify children with an increased chance of spontaneous clearance or sustained virologic response achievement and vitamin D level as a potential predictor of treatment response in children. It is also important to develop non-invasive tests that can predict liver fibrosis. The existence of differences in the mechanisms leading to liver injury between children and adults creates new perspectives of action to reduce liver disease progression in children in the early years of life.

The impact of synbiotic administration through in ovo technology on the microstructure of a broiler chicken small intestine tissue on the 1^(st) and 42^(nd) day of rearing

Background： Application the innovative method which is in ovo technology provides a means of modulating the immune system at early embryonic stages. The aim of study was to determine influence of the in ovo stimulation, on d12 of incubation, with synbiotics（synbiotic 1-L. salivarius IBB3154 ＋ Bi^2tos, Clasado Ltd. and the synbiotic 2-L. plantarum IBB3036 ＋ lupin RFOs） on the microstructure of duodenum, jejunum and ileum in the 1^（st） and 42^（nd）day of rearing.Results： On the 1^（st） day of chickens life, in the duodenum of both experimental groups（SYN1 and SYN2）, a significantly higher and wider intestinal vil i as wel as a significantly larger absorbent surface of these villi were found in comparison with the Control group（P ≤ 0.01）. On the 42^（nd）day of rearing the beneficial effect of synbiotic 1 was reflected by the numerical y higher vil i（no statistical differences） with a larger surface（P ≤ 0.01） in the duodenum in the SYN1 group compare to the Control group. In the jejunum on the 1^（st） day of life, in the SYN1 group, significantly higher vil i than in the Control group, with a simultaneous decrease in the depth of crypts（P ≤ 0.01）, and also the largest width of vil i and their absorbent area（P ≤ 0.01） in comparison to the other groups were found. On the 42^（nd）day of life, in the jejunum, an increase in the height of the vil i whilst reducing the crypt depth in the SYN2 group was found（P ≤ 0.01）. In turn, in the SYN1 group, there were significantly more neutral goblet cel s observed compared with the control group（P ≤ 0.05）. In the ileum of 1-day-old chickens, the widest vil i（P ≤ 0.05） and the deepest crypts（P ≤ 0.01） were found in the SYN2 group. In the same group, there was also the least amount of neutral goblet cel s in comparison to the other groups（P ≤ 0.05）.Conclusions： We observed that synbiotic 1 and 2 beneficial y affected the examined characteristics on the 1^（st） and 42^（nd） day of life. The obtained results al ow us to conclude that the use of synbiotics significantly affect gut structure which should contribute to improvement in nutrient absorption by the gut.

Exertional esophageal pH-metry and manometry in recurrent chest pain

AIM: To investigate the diagnostic efficacy of 24-h and exertional esophageal pH-metry and manometry in patients with recurrent chest pain. METHODS: The study included 111 patients (54% male) with recurrent angina-like chest pain, non-respon- sive to therapy with proton pump inhibitors. Sixty-five (59%) had non-obstructive lesions in coronary artery angiography, and in 46 (41%) significant coronary artery narrowing was found. In all patients, 24-h esophageal pH-metry and manometry, and treadmill stress tests with simultaneous esophageal pH-metry and manometry monitoring were performed. During a 24-h examination the percentage of spontaneous chest pain (sCP) episodes associated with acid reflux or dysmotility (symptom index, SI) was calculated. Patients with SI > 50% for acid gastroesophageal reflux (GER) were classified as having GER-related sCP. The remaining symptomatic individuals were determined as having non-GER-related sCP. During the stress test, the occurrence of chest pain, episodes of esophageal acidification (pH < 4 for 10 s) and esophageal spasm with more than 55% of simultaneous contractions (exercise-provoked esophageal spasm or EPES) were noted. RESULTS: Sixty-eight (61%) individuals reported sCP during 24-h esophageal function monitoring. Eleven of these (16%) were classified as having GER-related sCP and 53/68 (84%) as having non-GER-related sCP. The exercise-provoked chest pain during a stress test occurred in 13/111 (12%) subjects. In order to compare the clinical usefulness of 24-h esophageal function monitoring and its examination limited only to the treadmill stress test, the standard parameters of diagnostic test evaluation were determined. The occurrence of GER- related or non-GER-related sCP was assumed as a "gold standard". Afterwards, accuracy, sensitivity and specificity were calculated. These parameters expressed a prediction of GER-related or non-GER-related sCP occurrence by the presence of chest pain, esophageal acidification and EPES. Accuracy, sensitivity and specificity of chest pain during the stress test predicting any sCP occurrence were 28%, 35% and 80%, respectively, predicting GER- related sCP were 42%, 0% and 83%, respectively, and predicting non-GER-related sCP were 57%, 36% and 83%, respectively. Similar values were obtained for exercise-related acidification with pH < 4 longer than 10 s in the prediction of GER-related sCP (44%, 36% and 92%, respectively) and EPES in relation to non-GER-related sCP (48%, 23% and 84%, respectively). CONCLUSION: The presence of chest pain, esophageal acidification and EPES had greater than 80% specificity to exclude the GER-related and non-GER-related causes of recurrent chest pain.

Interaction between early in ovo stimulation of the gut microbiota and chicken host-splenic changes in gene expression and methylation

Background:Epigenetic regulation of the gene expression results from interaction between the external environment and transcription of the genetic information encoded in DNA.Methylated CpG regions within the gene promoters lead to silencing of the gene expression in most cases.Factors contributing to epigenetic regulation include intestinal microbiota,which in chicken can be potently modified by in ovo stimulation.The main aim of this study was to determine global and specific methylation patterns of the spleen under the influence of host-microbiome interaction.Results:Fertilized eggs of two genotypes:Ross 308 and Green-legged Partridgelike were in ovo stimulated on d 12 of incubation.The injected compounds were as follows:probiotic-Lactococcus lactis subsp.cremoris IBB477,prebiotic-galactooligosaccharides,and synbiotic-combination of both.Chickens were sacrificed on d 42 post-hatching.Spleen was collected,RNA and DNA were isolated and intended to gene expression,gene methylation and global methylation analysis.We have proved that negative regulation of gene expression after administration of bioactive substances in ovo might have epigenetic character.Epigenetic changes depend on the genotype and the substance administered in ovo.Conclusion:Epigenetic nature of microbial reprogramming in poultry and extension of issues related to hostmicrobiome interaction is a new direction of this research.

Exercise-provoked esophageal motility disorder in patients with recurrent chest pain

AIM:To investigate the relationship between exerciseprovoked esophageal motility disorders and the prognosis for patients with chest pain.METHODS:The study involved 63 subjects with recurrent angina-like chest pain non-responsive to empirical therapy with proton pump inhibitor(PPI).In all,a coronary artery angiography,panendoscopy,24-h esophageal pH-metry and manometry,as well as a treadmill stress test with simultaneous esophageal pH-metry and manometry monitoring,were performed.Thirtyfive subjects had no significant coronary artery lesions,and 28 had more than 50% coronary artery narrowing.In patients with hypertensive esophageal motility disorders,a calcium antagonist was recommended.The average follow-up period was 977 ± 249 d.RESULTS:The prevalence of esophageal disorders,such as gastroesophageal reflux or diffuse esophageal spasm,was similar in patients both with and without significant coronary artery narrowing.Exercise prompted esophageal motility disorders,such as a decrease in the percentage of peristaltic and effective contractions and their amplitude,as well as an increase in the percentage of simultaneous and non-effective contractions.In 14(22%) patients the percentage of simultaneous contractions during the treadmill stress test exceeded the value of 55%.Using Kaplan-Meier analysis and the proportional hazard Cox regression model,it was shown that the administration of a calcium channel antagonist in patients with such an esophageal motility disorder significantly decreased the risk of hospitalization as a result of a suspicion of acute coronary syndrome after the 2.7-year follow-up period.CONCLUSION:In patients with chest pain non-responsive to PPIs,a diagnosis of exercise-provoked esophageal spasm may have the effect of lowering the risk of the next hospitalization.