Constipation and colonoscopy

Constipation is a significant sociomedical problem,which can be caused by various reasons.In the diagnostic approach to patients with constipation,the following data are usually sufficient:History,complete physical examination(including rectal examination),and additional diagnostic tests.A colonoscopy is not a necessary diagnostic method for all patients with constipation.However,if patients have alarm symptoms/signs,that suggest an organic reason for constipation,a colonoscopy is necessary.The most important alarm symptoms/signs are age>50 years,gastrointestinal bleeding,new-onset constipation,a palpable mass in the abdomen and rectum,weight loss,anemia,inflammatory bowel disease,and family history positive for colorectal cancer.Most endoscopists do not like to deal with patients with constipation.There are two reasons for this,namely the difficulty of endoscopy and the adequacy of preparation.Both are adversely affected by constipation.To improve the quality of colonoscopy in these patients,good examination techniques and often more extensive preparation are necessary.Good colonoscopy technique implies adequate psychological preparation of the patient,careful insertion of the endoscope with minimal insufflation,and early detection and resolution of loops.Bowel preparation for colonoscopy often requires prolonged preparation and sometimes the addition of other laxatives.

Influence of Interrupted Childhood Biographies on Health Development: Evaluation of the Scientific Literature on the Example of Being Taken into Care*

Background: An interrupted family history, as is the case after taking someone into care, can complicate collecting family anamnesis data. In addition, the interrupted family history itself could be considered part of a person’s risk profile. Aim and methods: Literature analysis was conducted to examine whether there are scientific studies on health development after placement in out-of-home-care in order to recognise any existing medical characteristics that may be relevant for internal medical care. Results: There are few scientific publications on the health development of people after being placed in out-of-home-care. Direct reactions to the stress of being taken into custody include nausea and fever. However, effects that go beyond the acute situation and last into adulthood have also been described, such as AD(H)D, asthma, diabetes, cancer, hypertension and cardiovascular diseases (myocardial infarction, stroke), epilepsy and increased overall mortality in adulthood. Studies show that not only previous experience but also the stress of being taken into care is triggers for this. Conclusion: Information about a previous institutionalisation can hence be important for internal medical practice. The available scientific literature shows heterogeneous study methodology and no group of people with experience of out-of-home-placement has yet been scientifically accompanied for a long time period. Further studies on this could help to better weigh up the consequences of omitting and conducting an intervention for child/youth protection as well as to improve the medical care for this group of people.

Primary gastric mucosa associated lymphoid tissue lymphoma: Clinical data predicted treatment outcome

AIM: To determine clinical characteristics and treatment outcome of gastric lymphoma after chemotherapy and immuno-chemotherapy. METHODS: Thirty four patients with primary gastric mucosa associated lymphoid tissue (MALT) lymphoma (Ann Arbor stages Ⅰ to Ⅳ) were enrolled. All had upper gastric endoscopy, abdominal ultrasonography, CT and H pylori status assessment (histology and serology). After anti-H pylori treatment and initial chemotherapy, patients were re-examined every 4 mo. RESULTS: Histological regression of the lymphoma was complete in 22/34 (64.7%) and partial in 9 (26.5%) patients. Median follow up time for these 31 responders was 60 mo (range 48-120). No regression was noted in 3 patients. Among the 25 (73.5%) H pylori positive patients, the eradication rate was 100%.CONCLUSION: Using univariate analysis, predictive factors for overall survival were international prognostic index (IPI) score, hemoglobin level, erythrocyte sedimentation rate (ESR), and platelet numbers (P < 0.005). In addition to this, Cox proportion hazard model differentiate IPI score, ESR, and platelets as predictors of survival.

Contraindications for video capsule endoscopy

Video capsule endoscopy(VCE) has been applied in the last 15 years in an increasing field of applications. Although many contraindications have been put into perspective, some precautions still have to be considered. Known stenosis of the gastrointestinal tract is a clear contraindication for VCE unless surgery is already scheduled or at least has been considered as an optional treatment modality. In patients with a higher incidence of stenosis, as in an established diagnosis of Crohn's disease, clinical signs of obstruction, prior radiation or surgical small bowel resection, a preceding test with the self-dissolving patency capsule can override this contraindication. Endoscopic placement of the capsule should be considered in patients with swallowing disorders to avoid aspiration. Esophageal or gastric motility disorders may require endoscopic capsule transport or application of prokinetics if the real-time viewer proofs delayed transit. In pregnant women, VCE should be restricted to urgent cases where diagnosis cannot be postponed after delivery, as data on safety are missing. There is theoretical and clinical evidence that patients with implanted cardiac devices such as a pacemaker, cardioverters or left heart assist devices, can safely undergo VCE in spite of still existing contraindication by manufacturers. Children from the age of 2 years have safely undergone VCE. Although video capsules are not proven safe with magnetic resonance imaging(MRI), first single cases of patients incidentally undergoing MRI with an incorporated capsule have been reported, showing susceptibility artifacts but no signs of clinical harm.

Chemosensitivity Testing of Circulating Epithelial Tumor Cells (CETC) in <i>Vitro</i>: Correlation to in <i>Vivo</i>Sensitivity and Clinical Outcome

Background: Chemotherapy is a mainstay of tumor therapy, however, it is predominantly applied according to empirically developed recommendations derived from statistical relapse rates occurring years after the treatment in the adjuvant situation and from progression-free interval data in the metastatic situation, without any possibility of individually determining the efficacy in the adjuvant situation and with loss of time and quality of life in the metastatic situation if the drugs chosen are not effective. Here, we present a method to determine the efficiency of chemotherapeutic drugs using tumor cells circulating in blood as the part of the tumor actually available in the patient’s body for chemosensitivity testing. Methodology/Principal Findings: After only red blood cell lysis, omitting any enrichment (analogous to other blood cell enumeration methods, including rare CD34 cells), the white cells comprising the circulating epithelial tumor cells (CETC) are exposed to the drugs in question in different concentrations and for different periods of time. Staining with a fluorescence-labeled anti-epithelial antibody detects both vital and dying tumor cells, distinguishing vital from dying cells through membrane permeability and nuclear staining with propidium iodide. Increasing percentages of dying tumor cells are observed dependent on time and concentration. The sensitivity can vary during therapy and was correlated with decrease or increase in CETC and clinical outcome. Conclusions/Significance: Thus, we are able to show that chemosensitivity testing of circulating tumor cells provides real-time information about the sensitivity of the tumor present in the patient, even at different times during therapy, and correlates with treatment success.

A summary of the pharmacologically tested aphrodisiac plants for sexual dysfunction

Sexual dysfunction is a disruption of normal sexual intercourse and may be a consequence of various organic and psychological disorders. It is the most frequent at patients with cardiovascular and neurological diseases, sedentary lifestyle, arterial hypertension, diabetes, obesity and metabolic syndrome, and may disrupt their emotional life. But, sexual dysfunction may occur simply because of the physical aging of the body. Physiologic changes that occur with aging will aff ect sexual function and could be exacerbated by the above-mentioned diseases. Except for the sexual counseling and standard medications (phosphodiesterase type 5 (PDE5)– inhibitors, local estrogen therapy), some of the herbal medicines (aphrodisiacs) may be helpful in the treatment of these patients making them emotionally younger and happier. In this review, we bring a list of the pharmacologically tested aphrodisiac plants. But, we have a lack of information about their mechanisms of action, drug interaction and safety profi le. Until the relevant information is collected, uses of these products may be risky to the human being and should be prescribed only in consultation with a specialist.

Novel insights regarding the role of noncoding RNAs in diabetes

Diabetes mellitus(DM)is a group of metabolic disorders defined by hyperglycemia induced by insulin resistance,inadequate insulin secretion,or excessive glucagon secretion.In 2021,the global prevalence of diabetes is anticipated to be 10.7%(537 million people).Noncoding RNAs(ncRNAs)appear to have an important role in the initiation and progression of DM,according to a growing body of research.The two major groups of ncRNAs implicated in diabetic disorders are miRNAs and long noncoding RNAs.miRNAs are singlestranded,short(17–25 nucleotides),ncRNAs that influence gene expression at the post-transcriptional level.Because DM has reached epidemic proportions worldwide,it appears that novel diagnostic and therapeutic strategies are required to identify and treat complications associated with these diseases efficiently.miRNAs are gaining attention as biomarkers for DM diagnosis and potential treatment due to their function in maintaining physiological homeostasis via gene expression regulation.In this review,we address the issue of the gradually expanding global prevalence of DM by presenting a complete and upto-date synopsis of various regulatory miRNAs involved in these disorders.We hope this review will spark discussion about ncRNAs as prognostic biomarkers and therapeutic tools for DM.We examine and synthesize recent research that used novel,high-throughput technologies to uncover ncRNAs involved in DM,necessitating a systematic approach to examining and summarizing their roles and possible diagnostic and therapeutic uses.

Molecular phenotypes of human parvovirus B19 in patients with myocarditis

AIM:To investigate molecular phenotypes of myocardial B19V-infection to determine the role of B19V in myocarditis and dilated cardiomyopathy(DCM).METHODS:Endomyocardial biopsies(EMBs) from 498 B19V-positive patients with myocarditis and DCMwere analyzed using molecular methods and functional experiments.EMBs were obtained from the University Hospitals of Greifswald and Tuebingen and additionally from 36 German cardiology centers.Control tissues were obtained at autopsy from 34 victims of accidents,crime or suicide.Identification of mononuclear cell infiltrates in EMBs was performed using immunohistological staining.Anti-B19V-IgM and anti-B19V-IgG were analyzed by enzyme-linked immunosorbent assay(ELISA).B19V viral loads were determined using in-house quantitative real-time polymerase chain reaction(PCR).For B19V-genotyping a new B19V-genotype-specific restriction fragment length polymorphism(RFLP)-PCR was established.B19V-genotyping was verified by direct DNAsequencing and sequences were aligned using BLAST and BioEdit software.B19V P6-promoter and HHV6-U94-transactivator constructs were generated for cell culture experiments.Transfection experiments were conducted using human endothelial cells 1.Luciferase reporter assays were performed to determine B19Vreplication activity.Statistical analysis and graphical representation were calculated using SPSS and Prism5 software.RESULTS:The prevalence of B19V was significantly more likely to be associated with inflammatory cardiomyopathy(iCMP) compared to uninflamed DCM(59.6% vs 35.3%)(P < 0.0001).The detection of B19V-mRNA replication intermediates proved that replication of B19V was present.RFLP-PCR assays showed that B19V-genotype 1(57.4%) and B19V-genotype 2(36.7%) were the most prevalent viral genotypes.B19V-genotype 2 was observed more frequently in EMBs with iCMP(65.0%) compared to DCM(35%)(P = 0.049).Although there was no significant difference in gender-specific B19V-loads,women were more frequently infected with B19V-genotype 2(44.6%) than men(36.0%)(P = 0.0448).Coinfection with B19V and other cardiotropic viruses was found in 19.2% of tissuesamples and was associated with higher B19V viral load compared to B19V-monoinfected tissue(P = 0.0012).The most frequent coinfecting virus was human herpes virus 6(HHV6,16.5%).B19V-coinfection with HHV6 showed higher B19V-loads compared to B19V-monoinfected EMBs(P = 0.0033),suggesting that HHV6 had transactivated B19V.In vitro experiments confirmed a 2.4-fold increased B19V P6-promoter activity by the HHV6 U94-transactivator.CONCLUSION:The finding of significantly increased B19V loads in patients with histologically proven cardiac inflammation suggests a crucial role of B19V-genotypes and reactivation of B19V-infection by HHV6-coinfection in B19V-associated iCMP.Our findings suggest that B19V-infection of the human heart can be a causative event for the development of an endothelial cell-mediated inflammatory disease and that this is related to both viral load and genotype.

Adjuvant therapy sparing in rectal cancer achieving complete response after chemoradiation

AIM:To evaluate the long-term results of conventional chemoradiotherapy and laparoscopic mesorectal excision in rectal adenocarcinoma patients without adjuvant therapy.METHODS:Patients with biopsy-proven adenocarcinoma of the rectum staged cT3-T4 by endoscopic ultrasound or magnetic resonance imaging received neoadjuvant continuous infusion of 5-fluorouracil for five weeks and concomitant radiotherapy.Laparoscopic surgery was planned after 5-8 wk.Patients diagnosed with ypT0N0 stage cancer were not treated with adjuvant therapy according to the protocol.Patients with ypT1-2N0 or ypT3-4 or N+were offered 5-fluorouracil-based adjuvant treatment on an individual basis.An external cohort was used as a reference for the findings.RESULTS:One hundred and seventy six patients were treated with induction chemoradiotherapy and 170underwent total mesorectal excision.Cancer staging of ypT0N0 was achieved in 26/170(15.3%)patients.After a median follow-up of 58.3 mo,patients withypT0N0 had five-year disease-free and overall survival rates of 96%(95%CI:77-99)and 100%,respectively.We provide evidence about the natural history of patients with localized rectal cancer achieving a complete response after preoperative chemoradiation.The inherent good prognosis of these patients will have implications for clinical trial design and care of patients.CONCLUSION:Withholding adjuvant chemotherapy after complete response following standard neoadjuvant chemoradiotherapy and laparoscopic mesorectal excision might be safe within an experienced multidisciplinary team.

PillCamColon2 after incomplete colonoscopy-A prospective multicenter study

AIM To evaluate the ability of PillCamColon2 to visualize colonic segments missed by incomplete optical colonoscopy(OC) and to assess the diagnostic yield.METHODS This prospective multicentre study included 81 patients from nine centres who underwent second-generation colon capsule endoscopy(CCE) following incomplete OC performed by an experienced gastroenterologist(> 1000 colonoscopies). Patients with stenosis were excluded. According to patient preferences, CCE was performed the following day(protocol A) after staying on clear liquids and 0.75 L Moviprep in the morning or within 30 d after new split-dose Moviprep(protocol B). Boosts consisted of 0.75 L and 0.25 L Moviprep, and phospho-soda was given as a rescue if the capsule was not excreted after seven hours.RESULTS Seventy-four patients were analysed(51% of them in group A; 49% in group B). Bowel cleansing was adequate in 67% of cases, and CCE could visualize colonic segments missed by incomplete colonoscopy in 90% of patients under protocol A and 97% of patients under protocol B(P = 0.35, n.s.). Significant polyps including adenocarcinoma were detected in 24% of cases. Detection rates for all polyps and significant polyps per patient were similar in both protocols. Polyps were found predominantly in the right colon(86%) in segments that were not reached by OC. Extracolonic findings-such as reflux esophagitis, suspected Barrett esophagus, upper GI-bleeding, gastric polyps, gastric erosions and angiectasia-were detected in eight patients. Pill Cam Colon2 capsule was retained in the ileum of one patient(1.4%) without symptoms and removed during an uneventful resection for unknown Crohn's disease that was diagnosed as the cause of anemia, which was the indication for colonoscopy. CCE was well tolerated. One patient suffered from selflimiting vomiting after consuming the phospho-soda.CONCLUSION Second-generation CCE using a low-volume preparation is useful after incomplete OC, and it allows for the detection of additional relevant findings, but cleansing efficiency could be improved.

Diabetic patients with chronic kidney disease: Non-invasive assessment of cardiovascular risk

The prevalence and burden of diabetes mellitus and chronic kidney disease on global health and socioeconomic development is already heavy and still rising.Diabetes mellitus by itself is linked to adverse cardiovascular events,and the presence of concomitant chronic kidney disease further amplifies cardiovascular risk.The culmination of traditional(male gender,smoking,advanced age,obesity,arterial hypertension and dyslipidemia)and non-traditional risk factors(anemia,inflammation,proteinuria,volume overload,mineral metabolism abnormalities,oxidative stress,etc.)contributes to advanced atherosclerosis and increased cardiovascular risk.To decrease the morbidity and mortality of these patients due to cardiovascular causes,timely and efficient cardiovascular risk assessment is of huge importance.Cardiovascular risk assessment can be based on laboratory parameters,imaging techniques,arterial stiffness parameters,ankle-brachial index and 24 h blood pressure measurements.Newer methods include epigenetic markers,soluble adhesion molecules,cytokines and markers of oxidative stress.In this review,the authors present several non-invasive methods of cardiovascular risk assessment in patients with diabetes mellitus and chronic kidney disease.

Prevalence and Factors Associated with Depression, Anxiety and Stress in IBD Patients Undergoing Intravenous Biological Therapy during the COVID-19 Pandemic-Montenegro Experience

Throughout its duration,the coronavirus disease 2019(COVID-19)pandemic has been affecting lives worldwide and has had a sizeable impact on mental health,particularly for those who already suffer from a chronic illnesses.Depression,Anxiety and Stress(DAS)are common psychiatric comorbidities in inflammatory bowel disease(IBD)patients.This study aims to determine the prevalence and risk factors for moderate and severe symptoms of DAS in IBD patients have been undergoing intravenous biological therapy(IvBTh)during the COVID-19 pan-demic.The study was conducted between September 1st and November 30th,2020 at the Clinical Center of Mon-tenegro-IBD unit,where all patients from Montenegro received the registered IvBTh.This case control study consists of 94 IBD patients that completed a validated questionnaire Depression,Anxiety and Stress Score-21(DASS-21).A total of 59 patients received tumor necrosis factor alpha inhibitors(anti-TNF therapy),while 35 received anti-integrin therapy.After we calculated the DASS-21 score,we divided the patients into two groups:those who had moderate and severe symptoms(if they had any of the mentioned DASS-21 subscale score above limit for moderate or more severe symptoms:DASS-21 Depression,higher than 14;DASS-21 Anxiety,higher than 10 and DASS-21 Stress,higher than 19)and those who did not have significant symptoms(DASS-21 subscale score did not exceed the limit).We also examined demographic data,data on IBD characteristics and COVID-19 data and their impact on mental disorders.Standard statistical processing tests were used to identify risk factors for examined mental disorders.Following the DASS-21 criteria,we diagnosed the least moderate depression in 19.1%,anxiety in 14.9%and stress in 20.2%patients.The multivariate analysis indicated there to be a statistically significant relation of being higher at risk of developing depression,anxiety and stress when suffering from an active form of IBD(OR 6.487;95%Cl 1.220–34.500,P=0.028).Almost one third(30.9%)of patients have at least one of the examined mental disorders during the COVID-19 pandemic.Particular attention and efforts must be better focused on patients who suffer from an active form of IBD during the ongoing COVID-19 pandemic.

Influence of Leakage from Non-Invasive Positive Pressure Ventilation Mask on FiO₂Value Delivered by Home Oxygen Therapy Concentrator: A Bench Study on Simulating Patients with Chronic Obstructive Pulmonary Disease

Introduction: During the application of non-invasive positive pressure ventilation (NPPV) therapy in home mechanical ventilation (HMV), leaks in the NPPV mask may occur owing to the position of the mask due to conditions such as skin disorders. Methods: To investigate whether such a leak affects FiO2 supplied to the alveoli, we simulated a patient with chronic obstructive pulmonary disorder during NPPV in HMV. In addition, FiO2 was measured in the portion assumed to be the mouth and lungs while setting the flow of the oxygen concentrator and leak amount based on a previous study. Results: FiO2 supplied to the lungs increased statistically significantly upon increasing the amount of leak (P Conclusions: We observed that FiO2 supplied to alveoli can be reduced by a leak in the NPPV mask. Because our results differ from those previously reported, we believe that further studies should reassess the selection of respirators and oxygen concentrators.

Multimodal nonlinear imaging of atherosclerotic plaques differentiation of triglyceride and cholesterol deposits

Cardiovascular diseases in general and atherothrombosis as the most common of its individualdisease entities is the leading cause of death in the developed countries.Therefore,visualizationand characterization of inner arterial plaque composition is of vital diagnostic interest,especilly for the early recognition of vulnerable plaques.Established clinical techniques provide valuablemorphological information but cannot deliver information about the chemicai composition ofindividual plaques.Therefore,spectroscopic imaging techniques have recently drawn consider-able attention.Based on the spectroscopic properties of the individual plaque components,as forinstance diferent types of lipids,the composition of atherosclerotic plaques can be analyzedqualitatively as well as quantitatively.Here,we compare the feasibility of multimodal nonlinearimaging combining,two-photon fluorescence(TPF),coherent anti-Stokes Raman scatering(CARS)and second-hamonic generation(SHG)microscopy to contrast composition and mor-phology of lipid deposits against the surrounding matrix of connective tissue with diffractionlimited spatial resolution.In this contribution,the spatial distribution of major constituents of the arterial wall and atherosclerotic plaques like elastin,collagen,triglycerides and cholesterol can be simultaneously visualized by a combination of nonlinear imaging methods,providing a powerful label-free complement to standard histopathological methods with great potential forin vivo application.

慢性总冠状动脉闭塞患者冠状动脉窃血的决定因素:供体动脉、侧支血管及微血管的阻力

Objectives: We aimed to assess the mechanisms of coronary steal by direct hemodynamic measurements of the collateral circulation in chronic total coronary occlusions(CTO). Background: Coronary steal may cause ischemia despite well-developed collaterals in coronary artery disease. Methods: Fifty-six patients were studied during recanalization of a CTO. Before recanalization, the fractional flow reserve in the donor artery(FFRD) at the takeoff of the collaterals and the coronary flow reserve were recorded. After crossing the occlusion, the distal coronary flow velocity was measured by a Doppler wire(APVOccl), and distal pressure by a pressure wire. Changes of these parameters were assessed during intravenous adenosine(140 μg/kg/min). Resistance indexes for the donor artery(RD), collaterals(RC), and microcirculation(RP) were calculated. Results: Adenosine caused a decrease of APVOccl(i.e., coronary steal, in 26 patients[group S], an increase in 19 patients[group R], and no change in 11 patients). The FFRD was lower in group S. RD and RC increased in group S, while RD did not change significantly and RC decreased in group R. Patients with steal had more severe regional dysfunction. Patients with steal but without an FFRD< 0.8 tended to have an impaired microvascular function. Conclusions: We could demonstrate that coronary steal in man is mainly due to a hemodynamically significant donor artery lesion, but can also occur due to an impaired vasodilatory reserve of the microcirculation in the absence of a donor artery lesion. Coronary steal may have an adverse influence on the preservation of myocardial function by collaterals.

Behavior of circulating epithelial tumor cells(CETC)and FISH(fluorescence in situ hybridisation)of epidermal growth factor receptor(EGFR)-gene amplification in lung cancer patients during the course of therapy

Introduction: Monitoring the response of CETC to therapy in lung cancer allows early detection of patients at risk of progression. Analysis of the EGFR-gene amplification in these cells may help to characterize patients who might benefit from tyrosine kinase inhibitors. Methods: CETCs were quantified at least twice during treatment from blood of 52 patients with advanced non small cell lung cancer (NSCLC) using fluorescence labelled anti-EpCAM. EGFR-gene amplification was analysed in these cells with double probe (EGFR/CEP7) using FISH analysis. Results: Progression of the tumor was observed in 30 of the 52 patients (58%). With respect to changes in CETCs during therapy and progression free survival 31 patients showed a decrease in CETCs, 2 developing a single brain metastasis and 12 progressive disease;20 patients showed an increase in CETC more than twofold 16 of which developed progressive disease. The difference was highly significant (p=0.007 Fisher’s exact test) irrespective of age, sex, tumor size, pathological type and therapy. Kaplan-Meier progression free survival was significantly different between patients with decreasing and increaseing CETC (p=0.038). 5/20 patients tested were positive for EGFR amplification with 85-100% of EpCAM positive cells showing this chromosomal abnormality. One patient could be followed during therapy with increasing CETC during therapy with bevacizumab followed by relapse. He subsequently received erlotinib resulting in a decrease in CETC and is still free of progress after 516 days. Conclusions: These results show that peripherally circulating tumor cells in patients with advanced NSCLC are influenced by systemic chemotherapy and an increase in spite of therapy is a marker of aggressiveness of the tumor cells. Determination of the EGFR amplification might help to better treat part of these patients.

Effective intrahepatic CD8＋ T-cell immune responses are induced by low but not high numbers of antigen-expressing hepatocytes

Liver infections with hepatotropic viruses, such as hepatitis B virus and hepatitis C virus are accompanied by viral persistence and immune failure. CD8＋ T cells are crucial mediators of the intrahepatic antiviral immune response. Chronic infections of the liver and other organs correlate with T-cell exhaustion. It was previously suggested that high antigen load could result in T-cell exhaustion. We aimed at elucidating the impact of different intrahepatic antigen loads on the quality of CD8＋ T-cell-mediated immunity by employing an infection-free transgenic mouse model expressing ovalbumin （Ova） as the target antigen. Adoptive transfer of OT-I cells induced a transient intrahepatic immune response toward both high and low Ova levels. However, antigen clearance was achieved only in mice expressing low antigen levels. In contrast, T cells exposed to high antigen levels underwent exhaustion and became depleted, causing antigen persistence. Moreover, when functional T cells were exposed to high intrahepatic antigen levels, a complete transition toward exhaustion was observed. Thus, this study shows that the antigen expression level in the liver correlates inversely with T-cell immunity in vivo and governs the efficiency of immune responses upon antigen presentation.