Miracle-dz/UniFAR-FTUs huggingface dataset:
Gliadin activates mucosal cell mediated immunity in cultured rectal mucosa from coeliac patients and a subset of their siblings

Background—CD3 and γδ cells in the rectal mucosa increase after local instillation of gluten in children with coeliac disease and in half of their siblings. Aim—To establish an in vitro system for assessing immunological changes induced by gluten in the rectum. Patients and Methods—Rectal biopsy specimens obtained from 13 treated coeliac children, nine of their siblings, and nine controls were cultured in vitro with a peptic-tryptic digest of gliadin or ovalbumin. CD3 and CD25 cells were counted, and the expression of adhesion molecules evaluated. Results—In the lamina propria of coeliac biopsy samples cultured with gliadin, but not in those from controls, the expression of vascular cell adhesion molecule 1 (VCAM-1) was enhanced, and the number of CD25 cells was significantly higher than in those cultured in medium alone; the density of intraepithelial CD3 cells was also significantly higher. No differences were noted in coeliac biopsy specimens cultured with ovalbumin. A discriminant analysis allowed correct classification of all controls and all coeliacs but one, but three of nine siblings were allocated to the coeliac group. Conclusions—Our data confirm that gliadin is able to activate cell mediated immunity in the rectal mucosa in coeliac patients and in a subset of their first degree relatives.
Preferential Loss of the Nonimprinted Allele for the ZAC1 Tumor Suppressor Gene in Human Capillary Hemangioblastoma

Capillary hemangioblastomas (CHBs) are vascular, usually benign, tumors of the CNS, occurring either as a component of familial von Hippel-Lindau (VHL) disease or as a sporadic entity. Both familial and sporadic forms of VHL-associated tumors involve inactivation of the VHL gene; for CHB, 20% to 50% of sporadic cases are affected. However, other molecular alterations involved in the pathogenesis of sporadic CHBs, which represent up to 70% of CHBs, remain largely unknown. We previously identified a minimal deleted area at 6q23-24 in CHB, and the present study focused on the ZAC1 gene (6q24-25). ZAC1 is a maternally imprinted tumor suppressor gene with antiproliferative properties. We investigated loss of heterozygosity (LOH), promoter methylation, and expression status of ZAC1 in mainly sporadic cases of CHB. Our LOH analysis with 6 microsatellite markers spanning the ZAC1 gene region revealed a high frequency (6 of 10, 60%) of LOH. The promoter methylation analysis detected predominance of the methylated ZAC1 sequence in the majority (9 of 10, 90%) of the tumors. Immunohistochemistry exhibited a strongly reduced expression of ZAC1 in stromal cells of all CHBs studied. Collectively, our current results indicate that the absence of the unmethylated ZAC1 sequence was highly concurrent with ZAC1 region LOH or 6q loss and with lack of ZAC1 expression, suggesting preferential loss of the nonimprinted, expressed ZAC1 allele in CHB. This novel finding highlights the importance of ZAC1 in development of CHB, particularly in non-VHL-associated cases.
Perceptions of Cardiac Risk Factors and Risk-Reduction Behavior in Women With Known Coronary Heart Disease

Background:Risk factor reduction has been linked to personal perceptions of risk, yet few data exist about women's personal perceptions of coronary heart disease (CHD) risk, especially women who have experienced a cardiac event or intervention. Objective:The purpose of this study was to explore perceptions of risk for CHD and to examine perceptions of risk-reducing behaviors in women with known CHD. Methods:Because women's attitudes are conceptualized to be embedded in their everyday practices, an interpretative qualitative approach was chosen to reveal this phenomenon. The purposive sample consisted of 7 women with CHD. Interviews were conducted and transcribed verbatim. Data collection continued until saturation occurred. Efforts were made to increase trustworthiness through participant review of transcripts, peer debriefing, and using field notes. Results:Three major themes emerged from the data: "out of sight, out of mind," "why doesn't he talk to me like that? " and "it's scary. " The women indicated their CHD was currently not a major problem because they were asymptomatic or did not "feel sick," which led to decreased focus on their CHD, including risk factor reduction. They expressed the desire to return to normal, rather than focus on the chronicity of CHD. Participants felt that physicians treated them differently because they were women and that their concerns were taken less seriously. They perceived that the patient-physician relationship lacked open dialogue. Fear was experienced by all women, and many feared the unknown, especially not knowing when something was wrong with their heart. Conclusions:Data indicated that, during stable periods in the CHD trajectory, women may not understand the chronicity of their disease and may not recognize the importance of reducing their risk for future cardiac events. Helping women understand CHD chronicity even when they may not feel sick may assist them in engaging in risk-reducing behaviors.
Automated, high‐throughput, in vivo analysis of visual function using the zebrafish

Background: Modern genomics has enabled the identification of an unprecedented number of genetic variants, which in many cases are extremely rare, associated with blinding disorders. A significant challenge will be determining the pathophysiology of each new variant. The Zebrafish is an excellent model for the study of inherited diseases of the eye. By 5 days post‐fertilization (dpf), they have quantifiable behavioral responses to visual stimuli. However, visual behavior assays can take several hours to perform or can only be assessed one fish at a time. Results: To increase the throughput for vision assays, we used the Viewpoint Zebrabox to automate the visual startle response and created software, Visual Interrogation of Zebrafish Manipulations (VIZN), to automate data analysis. This process allows 96 Zebrafish larvae to be tested and resultant data to be analyzed in less than 35 minutes. We validated this system by disrupting function of a gene necessary for photoreceptor differentiation and observing decreased response to visual stimuli. Conclusions: This automated method along with VIZN allows rapid, high‐throughput, in vivo testing of Zebrafish's ability to respond to light/dark stimuli. This allows the rapid analysis of novel genes involved in visual function by morpholino, CRISPRS, or small‐molecule drug screens. Developmental Dynamics 245:605–613, 2016. © 2016 Wiley Periodicals, Inc.
Effect of an acute moderate‐exercise session on metabolic and inflammatory profile of PPAR‐α knockout mice

Peroxisome proliferator‐activated receptors (PPARs) play a major role in metabolism and inflammatory control. Exercise can modulate PPAR expression in skeletal muscle, adipose tissue, and macrophages. Little is known about the effects of PPAR‐α in metabolic profile and cytokine secretion after acute exercise in macrophages. In this context, the aim of this study was to understand the influence of PPAR‐α on exercise‐mediated immune metabolic parameters in peritoneal macrophages. Mice C57BL/6 (WT) and PPAR‐α knockout (KO) were examined in non‐exercising control (n = 4) or 24 hours after acute moderate exercise (n = 8). Metabolic parameters (glucose, non‐esterified fatty acids, total cholesterol [TC], and triacylglycerol [TG]) were assessed in serum. Cytokine concentrations (IL‐1β, IL‐6, IL‐10, TNF‐α, and MCP‐1) were measured from peritoneal macrophages cultured or not with LPS (2.5 μg/mL) and Rosiglitazone (1 μM). Exercised KO mice exhibited low glucose concentration and higher TC and TG in serum. At baseline, no difference in cytokine production between the genotypes was observed. However, IL‐1β was significantly higher in KO mice after LPS stimulus. IL‐6 and IL‐1β had increased concentrations in KO compared with WT, even after exercise. MCP‐1 was not restored in exercised KO LPS group. Rosiglitazone was not able to reduce proinflammatory cytokine production in KO mice at baseline level or associated with exercise. Acute exercise did not alter mRNA expression in WT mice. Conclusion: PPAR‐α seems to be needed for metabolic glucose homeostasis and anti‐inflammatory effect of acute exercise. Its absence may induce over‐expression of pro‐inflammatory cytokines in LPS stimulus. Moreover, moderate exercise or PPAR‐γ agonist did not reverse this response.
Extracellular Ca2+ Promotes Odontoblastic Differentiation of Dental Pulp Stem Cells via BMP2‐Mediated Smad1/5/8 and Erk1/2 Pathways

Ca2+ is the main element of many pulp capping materials that are used to promote the regeneration of tertiary dentin, but the underlying molecular mechanism is not clear. In this study, we found that Ca2+ increased the expression of the odontoblastic differentiation marker gene DSPP and promoted odontoblastic differentiation and mineralization of DPSCs, but inhibited ALP activity. Ca2+ increases the expression of endogenous BMP2, which activates the Smad1/5/8 pathway and promotes the Smad1‐Runx2 and Runx2‐DSPP interaction in DPSCs. Inhibition of Smad1/5/8 with dorsomorphin partially blocked Runx2 activity; however, inhibition of the BMP2 receptor with Noggin nearly fully suppressed Runx2 activity. These results indicate that Ca2+ promotes cell differentiation mainly via BMP2‐mediated Smad‐dependent and Smad‐independent pathways. We then determined that the phosphorylation level of Erk1/2, but not JNK or p38, was significantly increased as a result of Ca2+ stimulation. Blockage of Erk1/2 was found to inhibit Runx2 activity, indicating that Ca2+ triggers the Erk1/2 pathway, which subsequently regulates Runx2 activity. In addition, inhibition of Erk1/2 differentially attenuated the phosphorylation levels of Smad1/5/8 and Smad2/3. Collectively, this study demonstrates that Ca2+ activates the BMP2‐mediated Smad1/5/8 and Erk1/2 pathways in DPSCs and that Smad1/5/8 and Erk1/2 signaling converge at Runx2 to control the odontoblastic differentiation of DPSCs. J. Cell. Physiol. 230: 2164–2173, 2015. © 2015 Wiley Periodicals, Inc.
Evaluation of methylglyoxal toxicity in human erythrocytes, leukocytes and platelets

Abstract Methylglyoxal (MG) is a reactive dicarbonyl metabolite originated mainly from glucose degradation pathway that plays an important role in the pathogenesis of diabetes mellitus (DM). Reactions of MG with biological macromolecules (proteins, DNA and lipids) can induce cytotoxicity and apoptosis. Here, human erythrocytes, leukocytes and platelets were acutely exposed to MG at concentration ranging from 0.025 to 10 mM. Afterwards, hemolysis and osmotic fragility in erythrocytes, DNA damage and cell viability in leukocytes, and the activity of purinergic ecto-nucleotidases in platelets were evaluated. The levels of glycated products from leukocytes and free amino groups from erythrocytes and platelets were also measured. MG caused fragility of membrane, hemolysis and depletion of amino groups in erythrocytes. DNA damage, loss of cell viability and increased levels of glycated products were observed in leukocytes. In platelets, MG inhibited the activity of enzymes NTPDase, 5′-nucleotidase and adenosine deaminase (ADA) without affecting the levels of free amino groups. Our findings provide insights for understanding the mechanisms involved in MG acute toxicity towards distinct blood cells.
Supporting breast self-examination in female childhood cancer survivors: a secondary analysis of a behavioral intervention.

PURPOSE/OBJECTIVES To identify intervention targets that will increase the frequency of breast self-examination (BSE) in female survivors of childhood cancer. DESIGN Secondary data analysis of longitudinal clinical trial data. SETTING Outpatient clinic in a children's research hospital. SAMPLE 149 female survivors (aged 12-18 years) a median of 11 years after diagnosis of leukemia or lymphoma (59%) or solid tumor (41%). METHODS Paired t tests, Wilcoxon signed rank tests, repeated measures analysis of variance, and analysis of covariance. MAIN RESEARCH VARIABLES BSE frequency, health risk perceptions, motivation, and fears or worries. FINDINGS Baseline BSE frequency was the strongest influence on follow-up BSE. Baseline and follow-up age and school grade influenced follow-up BSE. Other influential variables included motivation for behavior change, motivation to commit to health promotion, concern about appearance, and an interaction between the intervention and mother's highest grade level. When baseline BSE frequency and school grade were statistically controlled, diagnosis and significant interactions between grade level and the follow-up measures of the mother's education, general fears about cancer, fears about cancer returning, and perceptions of susceptibility to late treatment effects were significant influences on BSE after intervention. CONCLUSIONS Survivors least likely to perform BSE are fearful about cancer and are not motivated to change health behaviors. IMPLICATIONS FOR NURSING Nurses should explore survivors' fears about cancer and late treatment effects to address misconceptions, use modeling techniques with return demonstrations to ensure competency in BSE, and tailor risk information to each survivor's background (socio-economic status, age, development) and cognitive (disease and treatment knowledge, risks) and affective (fears) characteristics to increase BSE motivation.
An updated list of the ticks of Ghana and an assessment of the distribution of the ticks of Ghanaian wild mammals in different vegetation zones

Abstract Twenty one species of ticks belonging to five genera of the family Ixodidae (Order Acari, sub-order Ixodida) – Amblyomma, Haemaphysalis, Hyalomma, Ixodes and Rhipicephalus (including the sub-genus Rhipicephalus (Boophilus)) – were collected from 1260 mammals, representing 29 species, 14 families and 6 orders, in four vegetation zones in Ghana during the period 1971–1978. Four other species were collected from humans in 1977. In all, eight species appeared to be new records for Ghana: Amblyomma tholloni Neumann; Dermacentor circumguttatus Neumann; Haemaphysalis houyi Nuttall & Warburton; Ixodes loveridgei Arthur; Ixodes oldi Nuttall; Ixodes vanidicus Schultze; Rhipicephalus complanatus Neumann; Rhipicephalus cuspidatus Neumann. The updated list of tick species in Ghana given here includes 41 species of ixodid ticks and four species of argasid ticks. Most species have been found in neighbouring regions of West Africa but 56 of the 121 different combinations of ixodid tick species and host species found in the collection described here have not apparently been reported before. The new combinations recorded here bring the total number of different combinations of ixodid tick species and mammalian host species now reported in Ghana to 151. The tick species found on wild mammals in Ghana mostly differed from those reported from domestic stock by other authors. The data showed that different tick species occurred in different vegetation zones and that most species displayed a pronounced preference for certain groups of related host species. Some tick species were found in the savanna feeding mainly on large bovids and/or suids; others were found in forests feeding mainly on small bovids, large rodents or small carnivores.
Removal of antibodies from red cells: Comparison of three elution methods

Background: Direct antiglobulin test (DAT) is the most common test done in immunohematology lab, which detects immunoglobulin and fragments of complement attached to the red blood cells. These coated red blood cells are difficult to accurately phenotype, which may be required for selection of appropriate unit of red blood cells for transfusion. Aims: We have studied the efficacy of various elution methods in removing the antibodies coating the red cells and their impact on different blood group antigen activity. Materials and Methods: Patient samples sent for serological evaluation of autoimmune hemolysis were included in the study. DAT and Indirect antiglobulin test (IAT) were performed using gel cards (ID system, DiaMed Switzerland). Antibody coated red cells, either by in-vivo or in-vitro sensitization, were used to assess the outcome of three elution methods. Results: Out of 93 DAT positive samples already sensitized in vivo, 28 (30 %) samples became DAT negative post elution using either of three methods, while 36 (38.8%) showed reduction in strength of reaction, whereas in 29 (31.2%) there was no change in strength of reaction. Similarly, out of the 17 samples prepared by in vitro sensitization, 12 samples became completely negative after glycine-HCl/EDTA elution, 9 and 5 samples became negative after heat elution and chloroquine diphosphate elution methods, respectively. Conclusion: On comparative analysis glycine-HCl/EDTA elution method was better than the other two methods and can be used for eluting immunoglobulins from intact red cells.
Spectral analysis of sustained pupil light response to short and long wavelength light

The purpose of this study was to assess the characteristics of frequency domain analysis of the sustained phase of pupil light reflex (PLR) to short and long wavelength light. In the work to be presented, spectra of the sustained phase of the PLR to short- and long- wavelength light in low and high photopic conditions were tested. The findings show that the proposed analysis method is valid and reveals significant differences between the analyzed cases. The findings suggest that the technique can provide useful information about the sustained phase of PLR which is always observed during PLR response to long light stimuli. Moreover, the proposed analysis method can be considered as a new, additional approach for testing the intrinsically photo-sensitive retinal ganglion cell activity mechanism.
Nocturnal periodic breathing at altitudes of 6,300 and 8,050 m.

Nocturnal periodic breathing was studied in eight well-acclimatized subjects living at an altitude of 6,300 m [barometric pressure (PB) 350-352 Torr] for 3-5 wk and in four subjects during one night at 8,050 m altitude (PB 281-285 Torr). The measurements at 6,300 m included tidal volume by inductance plethysmography, arterial O2 saturation by ear oximetry (calibrated by arterial blood samples), electrocardiogram (ECG), and electrooculogram. At 8,050 m, periodic breathing was inferred from the cyclical variation in heart rate obtained from a night-long ECG record. All subjects at 6,300 m altitude showed well-marked periodic breathing with apneic periods. Cycle length averaged 20.5 s with 7.9 s apnea. Minimal arterial O2 saturation averaged 63.4% corresponding to a PO2 of approximately 33 Torr, i.e., approximately 6 Torr lower than the normal value at rest during daytime. This was probably the most severe hypoxemia of the 24-h period. At 8,050 m altitude, the cycle length averaged 15.4 s, much longer than predicted by a theoretical model. Cyclical variations in heart rate caused by periodic breathing occurred in all subjects, but abnormal cardiac rhythms such as ventricular premature contractions were uncommon. The severe arterial hypoxemia caused by periodic breathing may be an important determinant of tolerance to these great altitudes.
Cell Surface Expression of Bacterial Esterase A by Saccharomyces cerevisiae and Its Enhancement by Constitutive Activation of the Cellular Unfolded Protein Response

ABSTRACT Yeast cell surface display is a powerful tool for expression and immobilization of biocatalytically active proteins on a unicellular eukaryote. Here bacterial carboxylesterase EstA from Burkholderia gladioli was covalently anchored into the cell wall of Saccharomyces cerevisiae by in-frame fusion to the endogenous yeast proteins Kre1p, Cwp2p, and Flo1p. When p-nitrophenyl acetate was used as a substrate, the esterase specific activities of yeast expressing the protein fusions were 103 mU mg−1 protein for Kre1/EstA/Cwp2p and 72 mU mg−1 protein for Kre1/EstA/Flo1p. In vivo cell wall targeting was confirmed by esterase solubilization after laminarinase treatment and immunofluorescence microscopy. EstA expression resulted in cell wall-associated esterase activities of 2.72 U mg−1 protein for Kre1/EstA/Cwp2p and 1.27 U mg−1 protein for Kre1/EstA/Flo1p. Furthermore, esterase display on the yeast cell surface enabled the cells to effectively grow on the esterase-dependent carbon source glycerol triacetate (Triacetin). In the case of Kre1/EstA/Flo1p, in vivo maturation within the yeast secretory pathway and final incorporation into the wall were further enhanced when there was constitutive activation of the unfolded protein response pathway. Our results demonstrate that esterase cell surface display in yeast, which, as shown here, is remarkably more effective than EstA surface display in Escherichia coli, can be further optimized by activating the protein folding machinery in the eukaryotic secretion pathway.
Anal verrucous carcinoma is not related to infection with human papillomaviruses and should be distinguished from giant condyloma (Buschke–Löwenstein tumour)

Verrucous carcinoma (VC) is a variant of well‐differentiated squamous cell carcinoma and in the anal region is regarded as synonymous with giant condyloma (Buschke–Löwenstein tumour) (BLT). Aetiology, diagnostic criteria and clinical behaviour of both lesions are controversial. Recent studies suggest that VC at other sites is not associated with human papillomaviruses (HPV). We hypothesized that anal VC is also not related to HPV, while BLT is a HPV‐induced lesion.
Quality of life in adults with cystic fibrosis: the Greek experience.

INTRODUCTION Recent developments in treatment have steadily raised the median predicted age of survival for people with Cystic Fibrosis (CF). We report the health-related quality of life (HRQoL) in CF adult patients and correlate our findings with the patients' demographic characteristics. MATERIAL AND METHODS The Cystic Fibrosis Quality of Life (CFQoL) questionnaire was answered by 77 CF adult patients. The questionnaire included questions pertaining to age, sex and level of education and covered eight sections of functioning. RESULTS The highest score was reported in the "Social Functioning" section, while the lowest in the "Concerns for the Future" section. When different age groups were compared, statistical significances were reported in "Physical Functioning", "Interpersonal Relationships", and the "Career Concerns" section, with older patients reporting statistically higher HRQoL scores than younger ones (p < 0.005). No statistically significant difference was reported amongst the scoring between male and female CF patients. When different educational levels were compared, patients that had received a higher educational training scored statistically higher in all but one sections of the questionnaire when compared with patients of a lower educational level (p < 0.005). CONCLUSION More than half Greek adult CF patients report that they are capable to participate in social activities but most of them are worried about the outcome of their disease and its effect on their lives.