Miracle-dz/UniFAR-FTUs huggingface dataset:
Trypsinogen IV, serotonin transporter transcript levels and serotonin content are increased in small intestine of irritable bowel syndrome patients

Abstract Colorectal and small intestinal visceral hypersensitivity has been demonstrated in irritable bowel syndrome (IBS). Serine protease signalling via protease‐activated receptor (PAR)‐2 promotes hyperalgesia to mechanical distension. Furthermore, serotonergic pathways are involved in gastrointestinal visceral sensitivity. Abnormalities of serine protease and serotonergic signalling components have been identified in IBS colorectal mucosal biopsies. We determined the role of altered mucosal serine protease and serotonergic signalling in small intestine of IBS patients. Duodenal mucosal biopsies of 34 IBS patients (10 constipation‐,11 diarrhoea‐predominant and 13 alternating) and 20 healthy subjects (HS) were collected. Gene transcripts of PAR‐2, trypsinogen IV, TPH‐1, SERT (serotonin transport protein) and serotonin (5‐HT3) subunits were quantified using real‐time PCR and 5‐HT content was measured by ELISA. Irritable bowel syndrome patients showed 1.5‐fold higher trypsinogen IV mRNA level compared to HS (P = 0.016). SERT expression was 1.8‐fold higher in IBS compared to HS (P = 0.007). Mucosal 5‐HT content was 1.7‐fold higher in IBS compared to HS (P = 0.015). The increase was 2.1‐fold in IBS‐C relative to HS (P = 0.018). Transcript levels of PAR‐2, TPH‐1 and 5‐HT3 receptor subunits did not differ between IBS and HS. In conclusion enhanced trypsinogen IV expression in IBS may cause increased PAR‐2 activation. Increased SERT expression and mucosal 5‐HT content in IBS suggest higher 5‐HT availability. Both may contribute to small intestinal visceral hypersensitivity in IBS patients.
The relative importance of the X‐linked FCP locus and β‐globin haplotypes in determining haemoglobin F levels: a study of SS patients homozygous for βS haplotypes

Five factors have been hypothesized to influence the 20‐fold variation in fetal haemoglobin (Hb F) levels in sickle cell anaemia (SS): age sex, α‐globin gene number, β‐globin haplotype, and the X‐linked F‐cell production locus (FCP) that regulates the production of Hb F containing erythrocytes (F cells). We analysed the association of these factors with Hb F levels in 112 SS patients living in France who are homozygous for the three common African β‐globin haplotypes (Benin, Bantu or Central African Republic and Senegal). We found that: (1) FCP accounts for about 40% of the overall variation in Hb F levels, (2) when the FCP influence is removed, β‐globin haplotype is associated with 14% of the remaining Hb F variation, and (3) the other factors have little influence. Comparison with our previous study of SS individuals in Jamaica leads to the following conclusions: (1) the X‐linked FCP locus is a major determinant of Hb F levels in SS disease, (2) factors linked to the β‐globin haplotype have only a small effect on the variation in Hb F levels, in either the homozygous or heterozygous state, and (3) approximately half of the variation in Hb F levels still remains to be explained.
Adenylyl cyclases in oocyte maturation: A characterization of AC isoforms in bovine cumulus cells

Mammalian oocytes are arrested at the G2/M transition in the meiotic cell cycle. It is well known that a decrease in intraoocyte cAMP concentrations accompanies resumption of meiosis, but the precise trigger of this decrease remains a mystery. Follicular somatic cells are intimately coupled to the oocyte and are thought to transmit maturation signals to the oocyte in response to hormonal stimulation. Here, we investigate the nature of the follicular somatic cell response to hormonal stimulation by identifying and characterizing the adenylate cyclase isoforms present in bovine cumulus cells. RT‐PCR and Western blot analysis revealed the presence of multiple adenylyl cyclase isoforms in bovine granulosa and cumulus cells. Pharmacological manipulation of the AC isoforms showed that multiple isoforms were indeed active. Our data indicate that the PKC inhibited adenylate cyclases IV and VI and the calcium‐stimulated isoform I predominate in bovine cumulus cells. Mol. Reprod. Dev. 1202–1210, 2006. © 2006 Wiley‐Liss, Inc.
The Effect of Hepatitis C Treatment Response on Medical Costs: A Longitudinal Analysis in an Integrated Care Setting

BACKGROUND: Studies suggest that chronic hepatitis C patients who achieve sustained virologic response (SVR) have lower risks of liver-related morbidity and mortality. Given the substantial costs and complexity of hepatitis C virus (HCV) antiviral treatment, post-treatment benefits are important to understand. OBJECTIVES: To determine whether health care costs and utilization for up to 5 years after treatment differed between patients who achieved SVR and those who did not. METHODS: Kaiser Permanente Medical Care Program patients receiving HCV treatment with pegylated interferon and ribavirin (Peg-IFN/RBV) from 2002 to 2007 were retrospectively analyzed, excluding those with human immunodeficiency virus (HIV) or chronic hepatitis B. Health care utilization and costs for up to 5 years after treatment completion were derived from electronic records. We compared mean annual cost and overall post-treatment costs (standardized to year-2007 dollars), and yearly utilization counts between the SVR and non-SVR groups, adjusting for pretreatment costs, age, sex, baseline cirrhosis, and race using gamma and Poisson regression models. RESULTS: The 1,924 patients eligible for inclusion were a mean age of 50 years; 63% male; 58% white, non-Hispanic; 62% with genotype 1; and 48% who had achieved SVR. The mean duration of post-treatment time was 3 years, and patients without SVR incurred significantly higher health care costs than patients with SVR. For each post-treatment year, total adjusted costs were significantly higher in the non-SVR group than in the SVR group, with rate ratios (RRs) and 95% CIs ranging from 1.26 (95% CI, 1.13-1.40) to 1.64 (95% CI, 1.38-1.96), driven mostly by hospital and outpatient pharmacy costs. When all post-treatment years were considered collectively, the non-SVR group had significantly higher costs overall (RR=1.41; 95% CI, 1.17-1.69) and in each category of costs. The adjusted difference in yearly total mean costs was $2,648 (95% CI, 737-4,560). In post-treatment years 2-5, adjusted liver-specific laboratory test rates were 1.8 to 2.3 times higher in the non-SVR group than in the SVR group (each year, P less than 0.001). During post-treatment years 1-5, adjusted yearly liver-related hospitalization rates were up to 2.45 times higher (95% CI, 1.56-3.85), and medicine/GI clinic visit rates were up to 1.39 times higher (95% CI, 1.23-1.54) in the non-SVR group compared with the SVR group. CONCLUSIONS: Health care utilization and costs after HCV antiviral therapy with Peg-IFN/RBV, particularly for liver-related tests, outpatient drugs, and hospitalizations, were significantly lower for patients who achieved SVR than for those without SVR. Our observations are consistent with the potentially lower risk of severe liver disease among patients with SVR.
Case of Childhood Ataxia with Central Nervous System Hypomyelination with a Novel Mutation in EIF2B3 gene

A 4-year-old boy presented with loss of motor milestones following viral fever. On examination, the child had increased tone and exaggerated deep tendon reflexes. Magnetic resonance imaging of the brain showed white matter hyperintensities on T2-weighted images, which revealed partial inversion on fluid-attenuated inversion recovery images. Clinical exome sequencing revealed a novel homozygous mutation c.1270T>G: pCys424Gly in exon 11 of the EIF2B3 gene. This novel mutation is reported in this article along with a literature review.
Epigenetic markers for chemosensitivity and chemoresistance in pancreatic cancer—A review

Adjuvant first‐line gemcitabine monochemotherapy presents a standard treatment for patients with advanced pancreatic adenocarcinoma and improves overall survival in chemosensitive patients. Nonetheless, 6‐month progression‐free survival remains below 15%, despite interdisciplinary approaches. The success of gemcitabine treatment is disappointing and—in the absence of reliable tumor markers—challenging to quantify. Epigenetic alterations have been recently identified to take on important roles in cancer development and possibly cancer treatment. In this context, microRNAs are becoming increasingly acknowledged as useful biomarkers for classifying cancers and providing information on their chemo‐ and radiosensitivity. This review illustrates the potential of genetic and epigenetic markers in the prediction of chemosensitivity in pancreatic cancer patients and in the monitoring of their response rates to adjuvant therapy.
Static Rate-Optimal Scheduling of Iterative Data-Flow Programs via Optimum Unfolding

Rate-optimal compile-time multiprocessor scheduling of iterative dataflow programs suitable for real-time signal processing applications is discussed. It is shown that recursions or loops in the programs lead to an inherent lower bound on the achievable iteration period, referred to as the iteration bound. A multiprocessor schedule is rate-optimal if the iteration period equals the iteration bound. Systematic unfolding of iterative dataflow programs is proposed, and properties of unfolded dataflow programs are studied. Unfolding increases the number of tasks in a program, unravels the hidden concurrently in iterative dataflow programs, and can reduce the iteration period. A special class of iterative dataflow programs, referred to as perfect-rate programs, is introduced. Each loop in these programs has a single register. Perfect-rate programs can always be scheduled rate optimally (requiring no retiming or unfolding transformation). It is also shown that unfolding any program by an optimum unfolding factor transforms any arbitrary program to an equivalent perfect-rate program, which can then be scheduled rate optimally. This optimum unfolding factor for any arbitrary program is the least common multiple of the number of registers (or delays) in all loops and is independent of the node execution times. An upper bound on the number of processors for rate-optimal scheduling is given. >
Immunoglobulin synthesis in bullfrog larvae.

The antibody-synthesizing capacity of tadpoles (Rana catesbeiana) has been studied with sheep erythrocytes as antigen. Tadpoles can mount an immune response similar to that seen in higher vertebrates except for a slower kinetic profile. They could not, however, be stimulated to elicit a true anamnestic response. The antibody had characteristics indicating that it probably was all IgM like. Use of the hemolytic plaque technique with various lymphoid organs detected synthesis of antibody in spleen, lymph gland and thymus.
Effects of cochlear implants: a qualitative study

Abstract This qualitative study aimed to gain a deeper insight into the effects of cochlear implants on recipients' lives, as perceived by the recipients themselves. To obtain this insight, we used four open-ended questions. We invited 107 adult patients from two Norwegian implant centres. Of these, 74 returned completed questionnaires (69%). Recipients perceived that they had got ‘A new life’ with the implant. Contributing to this global category of effects were four other categories. These concerned subjects' interactions with the world around them, experience of themselves, ability to hear the world around them and finally certain device-related issues. Overall, psychological well-being was improved. The questionnaire described might prove a useful tool in the follow-up of patients. Copyright © 2009 John Wiley & Sons, Ltd.
Method Variance in Organizational Research

It has become widely accepted that correlations between variables measured with the same method, usually self-report surveys, are inflated due to the action of common method variance (CMV), despite a number of sources that suggest the problem is overstated. The author argues that the popular position suggesting CMV automatically affects variables measured with the same method is a distortion and oversimplification of the true state of affairs, reaching the status of urban legend. Empirical evidence is discussed casting doubt that the method itself produces systematic variance in observations that inflates correlations to any significant degree. It is suggested that the term common method variance be abandoned in favor of a focus on measurement bias that is the product of the interplay of constructs and methods by which they are assessed. A complex approach to dealing with potential biases involves their identification and control to rule them out as explanations for observed relationships using a variety of design strategies.
Quantitation of Epstein–Barr virus mRNA using reverse transcription and real‐time PCR

Monitoring of Epstein–Barr virus (EBV) infection and reactivation in immunocompromized patients (e.g., after organ or bone‐marrow transplantation) is based mainly on serological assays and detection of viral DNA. For further characterization of virus reactivation and monitoring of viral transcription we established real‐time RT‐PCR assays using TaqMan technology to sensitively quantify viral transcripts expressed at different times of the lytic cycle: for BZLF1, an immediate early transactivator initiating the transition from latency to lytic replication, for the DNA‐polymerase BALF5 and for the major viral glycoprotein gp350/220 (BLLF1). RNA‐isolation was optimized to eliminate contaminating DNA. Preparations were shown to be virtually DNA‐free for up to 106 copies of RNA. With our PCR systems, it is possible to detect 10 copies of DNA or 100 copies of RNA per reaction as shown with serial dilutions of DNA‐plasmids or in vitro transcribed RNA, respectively. This corresponds to a detection limit of 8 × 102 copies/106 peripheral blood mononuclear cells (PBMCs). Evaluation of this system showed that even in healthy carriers borderline levels of BLLF1 mRNA were sometimes detectable. In patients with acute infectious mononucleosis (IM) viral transcripts were regularly found in varying concentrations. Extremely high levels of all three mRNA species could be seen in a patient after bone‐marrow transplantation monitored during an episode of lymphoproliferation which regressed during treatment with acyclovir and transfusion of donor T‐cells. This sensitive and reproducible method to detect and quantify different transcripts of EBV can be used to closely monitor reactivation of EBV, e.g., in immunocompromized patients. J. Med. Virol. 74:612–618, 2004. © 2004 Wiley‐Liss, Inc.
ON THE RECONSTRUCTION OF CONTINUOUS-TIME MODELS FROM ESTIMATED DISCRETE-TIME MODELS OF STOCHASTIC PROCESSES

Abstract In this paper we study the the problem of reconstructing a continuous-time model from an identified discrete-time model of a continuous-time stochastic processes. We present new necessary and sufficient condition for the existence of the soluion. It is also shown that the solution is unique if it exists. The theory is applicable to multivariable processes. The ideas are then used to develop a continuous-time ARMA (CARMA) process modelling algorithm with guaranteed solution. The theoretical results are tested using numerical simulations.
The role of self-organization in the promotion of resilience in maltreated children

The dynamic nature of resilience necessitates that children from high-risk backgrounds who are functioning adaptively despite experiences of adversity must be examined over time. In the current investigation, the adaptation of school-age maltreated and nonmaltreated socioeconomically disadvantaged children was examined over 3 consecutive years. In accord with predictions, a higher percentage of nonmaltreated children than of maltreated children were found to be resilient. Moreover, a higher percentage of maltreated than of nonmaltreated children were shown to exhibit functioning consistently in the low adaptive range. Differential predictors of resilience were found in maltreated and nonmaltreated children. Specifically, for maltreated children, positive self-esteem, ego resilience, and ego overcontrol predicted resilient functioning, whereas relationship features were more influential for nonmaltreated children. These findings are discussed in relation to the unfolding of resilient self-organizational strivings in maltreated and nonmaltreated children.
Influence of hydrocortisone on gentamicin-induced nephrotoxicity in rats

Many risk factors associated with aminoglycoside nephrotoxicity have been identified in humans and experimental animals. They include an initial high rate of creatinine clearance, high initial peak levels in serum, age, sex, duration of therapy, liver disease, and renal infection. The concomitant administration of steroids has never been investigated. We evaluated the role of hydrocortisone on gentamicin-induced nephroxicity in a model of infused rats. We showed that hydrocortisone given over 3 days after the infusion did not modify the gentamicin half-life in the renal cortex, gentamicin-induced lysosomal phospholipidosis, or histopathology but did reduce significantly the 3H/DNA ratio on day 4 after gentamicin infusion. We concluded that hydrocortisone interferes with the postnecrotic cellular regeneration process, an important step that is responsible for the recovery of normal kidney structure following toxic injuries associated with aminoglycoside therapy.
Effect of cholestasis on regulation of cAMP synthesis by glucagon and bile acids in isolated hepatocytes.

Previously, we have reported that bile acids can directly inhibit hormone-induced adenosine 3',5'-cyclic monophosphate (cAMP) formation through a protein kinase C (PKC)-dependent mechanism [Bouscarel, B. , T.W. Gettys, H. Fromm, and H. Dubner. Am. J. Physiol. 268 (Gastrointest. Liver Physiol. 31): G300-G310, 1995]. Therefore, the regulation of cAMP synthesis by glucagon and bile acids was investigated in hepatocytes isolated after 2-day ligation of the common bile duct in Golden Syrian hamsters. The bile acid concentration was increased 30-fold in the serum, whereas it was not significantly different in the bile of duct-ligated vs. sham-operated hamsters. The glycine/taurine and cholate/chenodeoxycholate ratios were significantly increased fourfold and sevenfold, respectively, only in the serum of bile duct-ligated hamsters. Ligation of the bile duct decreased the efficacy of glucagon-stimulated cAMP synthesis by 40-50% without changing its potency. This attenuation of cAMP synthesis, which was also observed with forskolin, remained in the absence of any detectable amount of bile acids in the hepatocytes. The decrease in glucagon-stimulated cAMP production was also not attributable to changes in either the affinity or the number of receptors for this hormone. The potency and efficacy of the bile acids to inhibit glucagon-induced cAMP formation was also reduced in bile duct-ligated hamsters. The inhibitory regulation of cAMP synthesis through angiotensin II was similarly diminished after bile duct ligation. Although the total expression of PKC-alpha was not affected, an increased translocation by 60% from the cytosol to the membrane fraction was observed in hepatocytes isolated after bile duct ligation. Therefore, during cholestasis and prolonged exposure of the liver to bile acids, both the stimulatory and inhibitory regulatory, mechanisms of cAMP synthesis are compromised in an irreversible manner because the effects persist even after isolation of the hepatocytes. This decreased regulation of cAMP synthesis is possibly mediated through PKC-alpha activation.
Psychological consequences of longevity : The increasing importance of self-regulation in old

How do changes in life expectancy and longevity affect life-span development? This paper argues that historical increases in life expectancy primarily have an impact on the later and less on the earlier parts of the life span. Increased life expectancy is both a challenge and an opportunity for positive development. A perspective is outlined according to which self-regulation is a key factor for successful aging. Assuming a compensatory relationship of social norms/expectations and self-regulation for developmental regulation, processes such as setting, pursuing, and disengaging from personal goals should be particularly important in old age, a life phase that is characterized by being less normatively structured than younger phases. This argument is elaborated in the domains of social relations, leisure, and work. DOI: https://doi.org/10.1159/000189213 Posted at the Zurich Open Repository and Archive, University of Zurich ZORA URL: https://doi.org/10.5167/uzh-25684 Published Version Originally published at: Freund, Alexandra M; Nikitin, J; Ritter, J O (2009). Psychological consequences of longevity: The increasing importance of self-regulation in old age. Human Development, 52(1):1-37. DOI: https://doi.org/10.1159/000189213
Enzymatic and Non-Enzymatic Virulence Activities of Dermatophytes on Solid Media.

INTRODUCTION Dermatophytes are keratinophilic fungi causing superficial cutaneous infections that account 20-25% of the global population. As per literature search, there is a dearth in the study on virulence factors of dermatophytes from the Indian sub-continent and moreover the association of the virulence factors and the host tissue in vitro helps in understanding the host-pathogen interaction. AIM To analyse the enzymatic and non-enzymatic virulence activities of dermatophytes on solid media. MATERIALS AND METHODS A total of 11 isolates, three standard American Type Culture Collection (ATCC) strains- Trichophyton rubrum- 28188, Trichophyton mentagrophytes- 9533, Trichophyton tonsurans- 28942, one CBS KNAW Fungal Biodiversity Centre strain- Arthroderma grubyi- 243.66, five clinical isolates- T. rubrum, T. mentagrophytes, Trichophyton rubrum var. raubitschekii, Trichophyton interdigitale, Epidermophyton floccosum, and two laboratory isolates - Microsporum gypseum and Microsporum canis were screened for the production of virulence enzymes such as phospholipase, lipase, protease, gelatinase and non-enzyme virulence factors (haemolytic activity) of dermatophytes. The clinical isolates were identified from a tertiary care hospital, Chennai. These dermatophytes were tested upon specific substrates on solid media such as egg yolk, tween 80, bovine serum albumin, gelatin powder and sheep blood respectively. RESULTS The virulence activity of phospholipase, lipase, protease and gelatinase was observed from all the dermatophyte species. T. rubrum, T. rubrum ATCC strain, T. rubrum var. raubitschekii, T. mentagrophytes, T. mentagrophytes ATCC strain, T. interdigitale and A. grubyi CBS strain produced complete haemolysis, whereas other dermatophytes showed no haemolytic activity. CONCLUSION Phospholipase, lipase, protease and gelatinase act as enzymatic virulence marker and the T. rubrum complex, T. mentagrophytes complex and A. grubyi showed complete haemolysis and hence they may also act as a non-enzymatic virulence marker for dermatophytes.