Dysregulated TFR and TFH cells correlate with B-cell differentiation and antibody production in autoimmune hepatitis.

Follicular helper T (TFH) cell provides germinal centre (GC) B cell with critical signals for autoantibody production in the immunopathogenesis and progression of autoimmune hepatitis (AIH). However, the immunoregulatory functions of follicular regulatory T (TFR) cell in AIH are still unclear. The numbers of circulating TFR/TFH cells were measured in AIH patients. Moreover, we established experimental autoimmune hepatitis (EAH) model to examine the function of TFR cells on B-cell differentiation and autoantibody production in vivo and vitro. AIH patients had significantly increased numbers of TFH cells and decreased numbers of TFR cells as well as imbalanced TFR/TFH-type cytokines (IL-10, TGF-ß1 and IL-21) compared with healthy controls (HCs). In addition, TFR cell numbers negatively correlated with TFH cell numbers. Also, serum hypergammaglobulinaemia (IgG and IgM) concentration negatively correlated the levels of serum IL-21, but positively correlated with the levels of serum IL-10 in AIH patients. Furthermore, in comparison with control group, significantly higher frequencies of spleen TFR cells but lower frequencies of spleen TFH cells were detected in the EAH group. Further analysis found that TFR cells simultaneously express the phenotypic characteristics of Treg and TFH cells, but exercise as negative regulators of autoantibody production in vitro culture. Our findings demonstrated that dysregulated between TFR and TFH cells might cause excessive production of autoantibodies and destruction of the immune homeostasis, leading to the immunopathological process in AIH.

18F-FDG PET/CT Quantitative Parameters and Texture Analysis Effectively Differentiate Endometrial Precancerous Lesion and Early-Stage Carcinoma.

OBJECTIVE: This study evaluated the metabolic parameters and texture features of fluorodeoxyglucose positron emission tomography-computed tomography (PET/CT) for the diagnosis and differentiation of endometrial atypical hyperplasia (EAH), EAH with field cancerization (FC), and stage 1A endometrial carcinoma (EC 1a). MATERIALS AND METHODS: We retrospectively analyzed the metabolic parameters of PET/CT in 170 patients with diagnoses confirmed by pathology, including 57 cases of EAH (57/170, 33.53%), 45 cases of FC (45/170, 26.47%), and 68 cases of EC 1a (68/170, 40.0%). Then, the texture features of each tumor were extracted and compared with the metabolic parameters and pathological results using nonparametric tests and linear regression analysis. The diagnostic performance was assessed by the area under the curve (AUC) values obtained from receiver operating characteristic analysis. RESULTS: There were moderate positive correlations between the PET standardized uptake values (SUVpeak, SUVmax, and SUVmean) and postoperative pathological features with correlation coefficients (rs) of 0.663, 0.651, and 0.651, respectively (P < .001). Total lesion glycolysis showed relatively low correlation with pathological characteristics (rs = 0.476), whereas metabolic tumor volume and age showed the weakest correlations (rs = 0.186 and 0.232, respectively). To differentiate between the diagnosis of EAH and FC, SUVmax displayed the largest AUC of 0.857 (sensitivity, 82.2%; specificity, 84.2%). Five texture features were screened out as Percentile 40, Percentile 45, InverseDifferenceMoment_AllDirection_offset 1, InverseDifferenceMoment_angle 45_offset 4, and ClusterProminence_angle 135_offset 7 (P < .001) by linear model of texture analysis (AUC = 0.851; specificity = 0.692; sensitivity = 0.871). To differentiate between the diagnoses of FC and EC 1a, SUVpeak displayed the largest AUC of 0.715 (sensitivity, 67.6%; specificity, 77.8%), and 2 texture features were identified as Percentile 10 and CP_angle 135_offset 7 (AUC = 0.819; specificity = 0.871; sensitivity = 0.766; P < .001). CONCLUSIONS: SUVmax and SUVpeak had the highest diagnostic values for EAH, FC, and EC 1a compared with the other tested parameters. SUVmax, Percentile 40, Percentile 45, InverseDifferenceMoment_AllDirection_offset 1, InverseDifferenceMoment_angle 45_offset 4, and ClusterProminence_angle 135_offset 7 distinguished EAH from FC. SUVpeak, Percentile 10, and ClusterProminence_angle 135_offset 7 distinguished FC from EC 1a. This study showed that the addition of texture features provides valuable information for differentiating EAH, FC, and EC 1a diagnoses.

An ERF2-like transcription factor regulates production of the defense sesquiterpene capsidiol upon Alternaria alternata infection.

Capsidiol is a sesquiterpenoid phytoalexin produced in Nicotiana and Capsicum species in response to pathogen attack. Whether capsidiol plays a defensive role and how its biosynthesis is regulated in the wild tobacco Nicotiana attenuata when the plant is attacked by Alternaria alternata (tobacco pathotype), a notorious necrotrophic fungus causing brown spot disease, are unknown. Transcriptome analysis indicated that a metabolic switch to sesquiterpene biosynthesis occurred in young leaves of N. attenuata after A. alternata inoculation: many genes leading to sesquiterpene production were strongly up-regulated, including the capsidiol biosynthetic genes 5-epi-aristolochene synthase (EAS) and 5-epi-aristolochene hydroxylase (EAH). Consistently, the level of capsidiol was increased dramatically in young leaves after fungal inoculation, from not detectable in mock control to 50.68±3.10 µg g-1 fresh leaf at 3 d post-inoculation. Capsidiol-reduced or capsidiol-depleted plants, which were generated by silencing EAHs or EASs by virus-induced gene silencing, were more susceptible to the fungus. In addition, this sesquiterpene when purified from infected plants exhibited strong anti-fungal activities against A. alternata in vitro. Furthermore, an ERF2-like transcription factor was found to positively regulate capsidiol production and plant resistance through the direct transactivation of a capsidiol biosynthetic gene, EAS12. Taken together, our results demonstrate that capsidiol, a phytoalexin highly accumulated in N. attenuata plants in response to A. alternata infection, plays an important role in pathogen resistance independent of jasmonate and ethylene signaling pathways, and its biosynthesis is transcriptionally regulated by an ERF2-like transcription factor.

A Single-Amino-Acid Substitution at Position 225 in Hemagglutinin Alters the Transmissibility of Eurasian Avian-Like H1N1 Swine Influenza Virus in Guinea Pigs.

Efficient transmission from human to human is the prerequisite for an influenza virus to cause a pandemic; however, the molecular determinants of influenza virus transmission are still largely unknown. In this study, we explored the molecular basis for transmission of Eurasian avian-like H1N1 (EAH1N1) swine influenza viruses by comparing two viruses that are genetically similar but differ in their transmissibility in guinea pigs: the A/swine/Guangxi/18/2011 virus (GX/18) is highly transmissible by respiratory droplet in guinea pigs, whereas the A/swine/Heilongjiang/27/2012 virus (HLJ/27) does not transmit in this animal model. We used reverse genetics to generate a series of reassortants and mutants in the GX/18 background and tested their transmissibility in guinea pigs. We found that a single-amino-acid substitution of glycine (G) for glutamic acid (E) at position 225 (E225G) in the HA1 protein completely abolished the respiratory droplet transmission of GX/18, whereas the substitution of E for G at the same position (G225E) in HA1 enabled HLJ/27 to transmit in guinea pigs. We investigated the underlying mechanism and found that viruses bearing 225E in HA1 replicated more rapidly than viruses bearing 225G due to differences in assembly and budding efficiencies. Our study indicates that the amino acid 225E in HA1 plays a key role in EAH1N1 swine influenza virus transmission and provides important information for evaluating the pandemic potential of field influenza virus strains.IMPORTANCE Efficient transmission among humans is a prerequisite for a novel influenza virus to cause a human pandemic. Transmissibility of influenza viruses is a polygenic trait, and understanding the genetic determinants for transmissibility will provide useful insights for evaluating the pandemic potential of influenza viruses in the field. Several amino acids in the hemagglutinin (HA) protein of influenza viruses have been shown to be important for transmissibility, usually by increasing virus affinity for human-type receptors. In this study, we explored the genetic basis of the transmissibility difference between two Eurasian avian-like H1N1 (EAH1N1) swine influenza viruses in guinea pigs and found that the amino acid glutamic acid at position 225 in the HA1 protein plays a critical role in the transmission of EAH1N1 virus by increasing the efficiency of viral assembly and budding.

Reassortant Eurasian Avian-Like Influenza A(H1N1) Virus from a Severely Ill Child, Hunan Province, China, 2015.

In 2015, a novel influenza A(H1N1) virus was isolated from a boy in China who had severe pneumonia. The virus was a genetic reassortant of Eurasian avian-like influenza A(H1N1) (EA-H1N1) virus. The hemagglutinin, neuraminidase, and matrix genes of the reassortant virus were highly similar to genes in EA-H1N1 swine influenza viruses, the polybasic 1 and 2, polymerase acidic, and nucleoprotein genes originated from influenza A(H1N1)pdm09 virus, and the nonstructural protein gene derived from classical swine influenza A(H1N1) (CS H1N1) virus. In a mouse model, the reassortant virus, termed influenza A/Hunan/42443/2015(H1N1) virus, showed higher infectivity and virulence than another human EA-H1N1 isolate, influenza A/Jiangsu/1/2011(H1N1) virus. In the respiratory tract of mice, virus replication by influenza A/Hunan/42443/2015(H1N1) virus was substantially higher than that by influenza A/Jiangsu/1/2011(H1N1) virus. Human-to-human transmission of influenza A/Hunan/42443/2015(H1N1) virus has not been detected; however, given the circulation of novel EA-H1N1 viruses in pigs, enhanced surveillance should be instituted among swine and humans.

A hydrogen bond network in the active site of Anabaena ferredoxin-NADP(+) reductase modulates its catalytic efficiency.

Ferredoxin-nicotinamide-adenine dinucleotide phosphate (NADP(+)) reductase (FNR) catalyses the production of reduced nicotinamide-adenine dinucleotide phosphate (NADPH) in photosynthetic organisms, where its flavin adenine dinucleotide (FAD) cofactor takes two electrons from two reduced ferredoxin (Fd) molecules in two sequential steps, and transfers them to NADP(+) in a single hydride transfer (HT) step. Despite the good knowledge of this catalytic machinery, additional roles can still be envisaged for already reported key residues, and new features are added to residues not previously identified as having a particular role in the mechanism. Here, we analyse for the first time the role of Ser59 in Anabaena FNR, a residue suggested by recent theoretical simulations as putatively involved in competent binding of the coenzyme in the active site by cooperating with Ser80. We show that Ser59 indirectly modulates the geometry of the active site, the interaction with substrates and the electronic properties of the isoalloxazine ring, and in consequence the electron transfer (ET) and HT processes. Additionally, we revise the role of Tyr79 and Ser80, previously investigated in homologous enzymes from plants. Our results probe that the active site of FNR is tuned by a H-bond network that involves the side-chains of these residues and that results to critical optimal substrate binding, exchange of electrons and, particularly, competent disposition of the C4n (hydride acceptor/donor) of the nicotinamide moiety of the coenzyme during the reversible HT event.

Eating in the absence of hunger in college students.

Nearly one-third of college students are overweight or obese. Disinhibited eating, a phenomenon defined as the lack of self-restraint over food consumption prompted by emotional or external factors, is prevalent among college students and may be a target for intervention in this population. Eating in the absence of hunger (EAH) is a form of disinhibited eating that has been studied extensively in children and adolescents, but there is little investigation of EAH among college students. In this research, a validated measure for assessing continual and beginning EAH in children and adolescents was modified and assessed in a free-living college population (n = 457; 84% F; 24.5 ± 7.6 years; 23.4 ± 4.8 kg/m(2)). Nine subscales grouped into three latent factors (emotion, external, and physical) accounted for 68% of the variance in continual EAH, and a separate set of nine subscales grouped into the same latent factors accounted for 71% of the variance in beginning EAH (Cronbach's alpha: 0.82 for continual EAH and 0.81 for beginning EAH). Female sex and sedentary behavior were significantly related to continual EAH, relationships driven by scores for the emotion factor, and to beginning EAH, relationships driven by scores for the physical factor. BMI was weakly related to the emotion factor (p = 0.06) for continuing EAH only. The observation that a sedentary lifestyle was associated to EAH (both continuing and beginning EAH) in a college population is a novel finding and reveals a possible strategy to moderate EAH.

Understanding eating in the absence of hunger among young children: a systematic review of existing studies.

BACKGROUND: Eating in the Absence of Hunger (EAH), or consuming highly palatable foods when satiated, is one behavioral pathway that may lead to childhood obesity. EAH is an objective, laboratory-based measure. A more comprehensive understanding of potential determinants of EAH could inform childhood obesity programs outside of a laboratory setting. OBJECTIVE: Systematic review of EAH experiments to identify individual, familial, and societal-level correlates of EAH among children 12 years of age or younger. DESIGN: 1487 studies were retrieved from five electronic databases (Medline [PubMed], Web of Science, Cochrane Library, CINAHL, PsycINFO). Eligible studies were those that measured EAH as initially operationalized in a laboratory setting enrolling children ≤12 years or reporting age-specific results for children ≤12 years. Only articles written in English were included. RESULTS: 12 cross-sectional, six prospective, and one behavioral-intervention studies were included in the review. EAH was observable among boys and girls; absolute levels of EAH increased with age; and maternal feeding styles were associated with EAH among girls. The most consistent evidence supported increased levels of EAH among overweight and obese versus normal weight children, both cross-sectionally and prospectively. Two studies supported a genetic component to EAH. CONCLUSIONS: Studies enrolling independent samples support a positive association between weight status and EAH among children; studies addressing causality are needed. Other various individual, genetic, and familiar characteristics were associated with EAH, yet studies among more heterogeneous sample populations are needed to confirm findings. Studies addressing societal-level factors related to EAH were absent.

Adult eczema prevalence and associations with asthma and other health and demographic factors: a US population-based study.

BACKGROUND: Little is known about the epidemiology of eczema in adults. The goal of this study was to determine the prevalence of and associations with adult eczema in the United States. METHODS: We used the 2010 National Health Interview Survey from a nationally representative sample of 27,157 adults age 18 to 85 years. RESULTS: Overall, the 1-year prevalence of eczema was 10.2% (95% CI, 9.7% to 10.6%). The 1-year prevalence of eczema with asthma and/or hay fever was 3.2% (95% CI, 2.8% to 3.3%). Adult eczema was associated with higher prevalence of asthma (P < .001, Rao-Scott χ(2) test), more asthma attacks in the past year (P < .001), and more persistent asthma (P = .02). In multivariate models eczema prevalence was significantly higher in older participants; female subjects; those with Hispanic ethnicity, US birthplace, and higher level of household education; and those currently working (all P ≤ .02, logistic regression). CONCLUSIONS: This study provides US population-based estimates of eczema prevalence and asthma associations in adults. The results suggest multiple demographic and socioeconomic influences on the US prevalence of adult eczema.

Symptomatic hypotonic hyponatremia presenting at high altitude.

We present a case of altered mental status and seizure that occurred at an altitude known to cause high altitude-related illnesses. Based on the presenting symptoms, the patient was initially transferred to the hospital with a presumptive diagnosis of high altitude cerebral edema. On review of imaging and laboratory data, she was found to be experiencing symptomatic hypotonic hyponatremia. This case presented an interesting diagnostic challenge and underscores the importance of maintaining a broad differential diagnosis when evaluating a patient with altered mental status from an alpine setting.

Exercise-associated Hyponatremia Developing Immediately after a Musical Stage Performance in a Healthy Actress.

Exercise-associated hyponatremia (EAH) is a life-threatening dilutional hyponatremia that typically occurs during or immediately after exercise in endurance athletes. A 49-year-old actress experienced dizziness 15 min after a 2-h stage performance while drinking several bottles of water. Thirty minutes later, the patient fell unconscious and was hospitalized. On admission, she showed dilutional hyponatremia (117 mmol/L) with extremely elevated arginine vasopressin (11.3 pg/mL). After initial treatment with 3% saline, her sodium levels immediately increased, and she recovered consciousness without developing subsequent osmotic demyelination syndrome. This case emphasizes the need for caution against excessive fluid intake during and/or after exercise to avoid EAH, even in non-athletes.

A Case of Adult-Onset Eccrine Angiomatous Hamartoma-The Comparison with Epithelioid Hemangioma.

Eccrine angiomatous hamartoma (EAH) is a relatively rare benign skin disease characterized by the proliferation of eccrine sweat glands associated with capillary hemangioma and the proliferation of other skin elements such as adipose tissue, hair, and epidermis. The onset of the disease is usually at birth or in childhood and tends to occur in the extremities of females, but it occurred in an adult male in this case. The patient was a 72-year-old man with a 12 × 12 mm light brown, elastic, slightly firm skin nodule on the flexor aspect of his right forearm. A biopsy revealed enlargement of blood vessels, sweat glands, sweat ducts, and erector spongiosum with both lumen dilation and narrowing, leading to the diagnosis of EAH. The histopathological features of EAH include a marked proliferation of microvessels, epithelial-like changes in vascular endothelial cells (such as enlarged nuclei), and infiltration of inflammatory cells, mainly lymphocytes and plasma cells. In adult-onset cases, EAH can be clinically difficult to distinguish from epithelioid hemangioma (EH), which differs in the predominance of microvascular proliferation and the presence of eosinophils in the infiltrating inflammatory cells. It can also be distinguished from EAH by the negative results of S100 and anti-EMA in immunohistological staining. In the current cases, we were able to differentiate the two cases from characteristic findings on HE staining.

Asterias pectinifera-Derived Collagen Peptides Mixed with Halocynthia roretzi Extracts Exhibit Anti-Photoaging Activities during Exposure to UV Irradiation, and Antibacterial Properties.

Asterias pectinifera, a species of starfish and cause of concern in the aquaculture industry, was recently identified as a source of non-toxic and highly water-soluble collagen peptides. In this study, we investigated the antioxidant and anti-photoaging functions of compounds formulated using collagen peptides from extracts of Asterias pectinifera and Halocynthia roretzi (AH). Our results showed that AH compounds have various skin protective functions, including antioxidant effects, determined by measuring the scavenging activity of 2,2-diphenyl-1-picrylhydrazyl radicals, as well as anti-melanogenic effects, determined by measuring tyrosinase inhibition activity. To determine whether ethosome-encapsulated AH compounds (E(AH)) exert ultraviolet (UV)-protective effects, human dermal fibroblasts or keratinocytes were incubated with E(AH) before and after exposure to UVA or UVB. E(AH) treatment led to inhibition of photoaging-induced secretion of matrix metalloproteinase-1 and interleukin-6 and -8, which are associated with inflammatory responses during UV irradiation. Finally, the antibacterial effects of AH and E(AH) were confirmed against both gram-negative and gram-positive bacteria. Our results indicate that E(AH) has the potential for use in the development of cosmetics with a range of skin protective functions.

Fecal Microbiota Transplantation Controls Progression of Experimental Autoimmune Hepatitis in Mice by Modulating the TFR/TFH Immune Imbalance and Intestinal Microbiota Composition.

Intestinal microbiota (IM) dysbiosis contributes to the development of autoimmune hepatitis (AIH). This study aimed to investigate the potential effect of fecal microbiota transplantation (FMT) in a murine model of experimental AIH (EAH), a condition more similar to that of AIH patients. Changes in the enteric microbiome were determined in AIH patients and EAH mice. Moreover, we established an experimental model of secondary EAH mice harboring dysbiosis (ABx) to analyze the effects of therapeutic FMT administration on follicular regulatory T (TFR) and helper T (TFH) cell imbalances and IM composition in vivo. Alterations of the IM composition and bacterial translocation occurred in AIH patients compared to nonalcoholic fatty liver disease patients and healthy controls (HCs). Therapeutic FMT significantly attenuated liver injury and bacterial translocation and improved the imbalance between splenic TFR cells and TFH cells in ABx EAH mice. Furthermore, therapeutic FMT also partially reversed the increasing trend in serum liver enzymes (ALT and AST) of CXCR5-/-EAH mice on the 28th day. Finally, therapeutic FMT could effectively restore antibiotic-induced IM dysbiosis in EAH mice. Taken together, our findings demonstrated that FMT was capable of controlling hepatitis progression in EAH mice, and the associated mechanism might be involved in the regulation of the TFR/TFH immune imbalance and the restoration of IM composition.

Association of AGTR1 (rs5186), VDR (rs2228570) genes polymorphism with blood pressure elevation in patients with essential arterial hypertension.

Essential arterial hypertension (EAH) is a polygenic disease due to environmental, genetic, and epigenomic factors. The study aimed to establish the association of single nucleotide polymorphism (SNP) of AGTR1 (rs5186) and VDR (rs2228570) genes with the blood pressure (BP) elevation in EAH patients. 100 EAH subjects with hypertensive-mediated organ damaging (2nd stage), moderate, high, or very high cardiovascular risk were recruited into the case-control study. There were 70.83% females and 29.17% males, mean age 57.86±7.81 y.o. The control group included 60 healthy individuals of relevant age and gender distribution. Estimation of AGTR1 (rs5186) and VDR (rs2228570) gene polymorphism was performed by Real-Time Polymerase Chain Reaction. In EAH patients, the AGTR1 gene (rs5186) mutation occurs with a frequency of 2.78% in the absence of such among healthy individuals. The VDR (rs2228570) gene mutation occurs with a frequency of 23% cases. The C-allele carriers' (AGTR1 gene) numbers with 2nd and 3rd BP values degree dominate over AA-genotype patients by 25.32% (χ2=4.52; p=0.033). VDR gene (rs2228570) polymorphic variants do not link to BP elevation values. Thus, the C-allele of the AGTR1 gene (rs5186) is associated with BP elevation in hypertensive patients. BP values do not depend on VDR gene (rs2228570) polymorphic variants.

Serum sodium changes in marathon participants who use NSAIDs.

INTRODUCTION: The primary mechanism through which the development of exercise-associated hyponatraemia (EAH) occurs is excessive fluid intake. However, many internal and external factors have a role in the maintenance of total body water and non-steroidal anti-inflammatory medications (NSAIDs) have been implicated as a risk factor for the development of EAH. This study aimed to compare serum sodium concentrations ([Na]) in participants taking an NSAID before or during a marathon (NSAID group) and those not taking an NSAID (control group). METHODS: Participants in a large city marathon were recruited during race registration to participate in this study. Blood samples and body mass measurements took place on the morning of the marathon and immediately post marathon. Blood was analysed for [Na]. Data collected via questionnaires included athlete demographics, NSAID use and estimated fluid intake. RESULTS: We obtained a full data set for 28 participants. Of these 28 participants, 16 took an NSAID on the day of the marathon. The average serum [Na] decreased by 2.1 mmol/L in the NSAID group, while it increased by 2.3 mmol/L in the control group NSAID group (p=0.0039). Estimated fluid intake was inversely correlated with both post-marathon serum [Na] and ∆ serum [Na] (r=-0.532, p=0.004 and r=-0.405 p=0.032, respectively). CONCLUSION: Serum [Na] levels in participants who used an NSAID decreased over the course of the marathon while it increased in those who did not use an NSAID. Excessive fluid intake during a marathon was associated with a lower post-marathon serum [Na].

Enlarged subarachnoid spaces and intracranial hemorrhage in children with accidental head trauma.

OBJECTIVE Benign external hydrocephalus (BEH) is an enlargement of the subarachnoid spaces (SASs) that can be seen in young children. It is controversial whether children with BEH are predisposed to developing subdural hemorrhage (SDH) with or without trauma. This issue is clinically relevant as a finding of unexplained SDH raises concerns about child abuse and often prompts child protection and law enforcement investigations. METHODS This retrospective study included children (1-24 months of age) who underwent head CT scanning after an accidental fall of less than 6 feet. Head CT scans were reviewed, cranial findings were documented, and the SAS was measured and qualitatively evaluated. Enlarged SAS was defined as an extraaxial space (EAS) greater than 4 mm on CT scans. Clinical measurements of head circumference (HC) were noted, and the head circumference percentile was calculated. The relationship between enlarged SAS and HC percentile, and enlarged SAS and intracranial hemorrhage (ICH), were investigated using bivariate analysis. RESULTS Of the 110 children included in this sample, 23 had EASs greater than 4 mm. The mean patient age was 6.8 months (median 6.0 months). Thirty-four patients (30.9%) had ICHs, including subarachnoid/subpial (6.2%), subdural (6.2%), epidural (5.0%), and unspecified extraaxial hemorrhage (16.5%). Enlarged SAS was positively associated with subarachnoid/subpial hemorrhage; there was no association between enlarged SASs and either SDH or epidural hemorrhage. A larger SAS was positively associated with larger HC percentile; however, HC percentile was not independently associated with ICH. CONCLUSIONS Enlarged SAS was not associated with SDH, but was associated with other ICHs. The authors' findings do not support the theory that BEH predisposes children to SDH with minor accidental trauma.

Angiomatous Hamartoma - A Rare Presentation.

Eccrine Angiomatous Hamartoma (EAH) is a benign rare skin neoplasm characterised histologically by abnormal proliferation of sweat glands and surrounding capillaries and other dermal elements like fatty lobules and hair. It usually presents at birth or in early childhood in the form of solitary nodules mostly affecting the extremities. Here, we report a case of angiomatous hamartoma over the face which presented as a cystic swelling in preauricular region in a 55-year-old man. The late onset and a rare site for presentation of EAH prompted us to report the case. There is not even a single case of EAH arising in the "preauricular" region, reported.

Celecoxib attenuates depressive-like behavior associated with immunological liver injury in C57BL/6 mice through TNF-α and NF-κb dependent mechanisms.

AIM: Depression associating patients with chronic liver diseases is a major treatment goal. This study aimed to evaluate the potential hepatoprotective and antidepressant effects of celecoxib in a model of experimental autoimmune hepatitis (EAH) and depressive-like behavior in C57BL/6 mice. MAIN METHODS: EAH was induced by immunization with S-100 liver antigen emulsified in complete Freund's adjuvant (CFA). Mice were randomly allocated to 5 groups; control phosphate buffered saline group; control CFA group; EAH group, and 2 groups of EAH plus celecoxib (7.5 or 15mg/kg/d respectively). Mice were assessed behaviorally by novelty-suppressed test, tail suspension test, locomotor assessment and forced swimming tests. Serum liver enzymes and hepatic hydroxyproline content were biochemically analyzed. Histopathological analysis for liver and brain sections and immunohistochemical studies for hepatic and hippocampal tumor necrosis factor (TNF-α), nuclear factor Kappa-B (NF-κB) and caspase-3 were performed. KEY FINDINGS: EAH group exhibited significant depressive-like changes, increase in liver enzymes and hepatic hydroxyproline content. Signs of autoimmune hepatitis and structural changes in hippocampus were confirmed by histopathological studies. Immunohistochemical examination revealed overexpression of hepatic and hippocampal TNF-α, NF-κB and caspase-3 positive cells. Celecoxib (7.5mg/kg/d) significantly ameliorated hepatic biochemical changes, hepatic and hippocampal histopathological and immunohistochemical changes induced in EAH group. Celecoxib (15mg/kg/d) significantly ameliorated the behavioral changes, histopathological and immunohistochemical changes in hippocampus, with non-significant change in hepatic biochemical profile, histopathological and immunohistochemical changes induced in EAH group. SIGNIFICANCE: The celecoxib (7.5mg/kg/d) through its anti-inflammatory effect may represent a new therapeutic approach to treat autoimmune hepatitis associated with depressive symptoms.