Re-evaluation of serum alanine aminotransferase upper normal limit and its modulating factors in a large-scale population study.

BACKGROUND: The upper normal limit (ULN) of serum alanine-aminotrasferase (ALT) normal range was recently challenged, because patients diagnosed with liver diseases may have 'normal' or near-'normal' ALT levels, and because possible modulators are often ignored in determining normal range. AIM: To estimate the ULN for serum ALT and to identify factors modulating it. SUBJECTS AND METHODS: We reviewed medical records of subjects aged 15-90, who underwent standard panels of laboratory tests, including serum ALT, over 6 months at a central laboratory. Three groups were defined: Group 1, comprised total study population (N=272 273). Group 2 (N=87 020) comprised total study population, excluding those receiving potentially hepatotoxic drugs, or diagnosed with liver disease, or had any abnormal laboratory test results other than for triglycerides, cholesterol, glucose, or HbA1c. Group 3 (N=17 496) the 'healthy' population, from whose ALT values we established the new ULN, comprised Group 2 subjects with normal triglycerides, cholesterol, glucose, and HbA1c levels. RESULTS: The 95th percentile ALT values, corresponding to the ULN, in groups 1, 2, and 3 were 50.1, 40, and 37.5 U/l, respectively. 6.2% (16 943/273 273) of subjects whose ALT was below ULN listed by the test manufacturer (52 U/l), had ALT level above our new ULN. Linear and logistic-regression analyses showed that ALT levels were significantly modified by gender, age, glucose, cholesterol, triglycerides, and overweight/obesity diagnosis. Significant interaction was found between gender, glucose and cholesterol levels. CONCLUSIONS: In this first large-scale study of 'healthy' population, serum ALT ULN was far lower than currently accepted value. Age and gender may be considered when determining the ULN for ALT.     

Zoonotic Dirofilaria repens (Nematoda: Filarioidea) in Aedes vexans mosquitoes,Czech Republic

The surveillance of vectors for arthropod-borne pathogens is nowadays an important tool in surveillance programmes throughout Europe. Whereas many studies have been performed to screen arthropods for viruses or bacterial pathogens, only limited information is available concerning the geographical distribution and vector range of pathogenic filariae in Central Europe. To consider the prevalence of filarial parasites in mosquito vectors, we performed a molecular survey of mosquitoes for filarial DNA. Mosquito collection was conducted at six study sites in the South Moravian region (Czech Republic) close to the borders with Slovakia and Austria from 2009 to 2011. Molecular screening of mosquitoes was conducted using conventional PCR with primers designed to amplify the mitochondrial cytochromoxidase subunit I gene as well as the partial 5.8S ribosomal RNA gene. A total of 13,222 mosquitoes belonging to six species were captured and distributed into 237 pools with different numbers of individuals. Overall, four pools were positive for Dirofilaria repens (a minimum infection rate 0.03 %) at two study sites (both natural and urban). Another filarial parasite detected during a study into Aedes vexans mosquitoes revealed the closest homology to Setaria spp. We detected specific D. repens DNA in Ae. vexans mosquitoes for the first time in the Czech Republic and confirmed the circulation of Dirofilaria spp. in a natural focus of infection providing an epidemiological link between autochthonous canine cases and mosquito vectors in the area studied.     

Up-regulation of gonadotropin mRNA-expression at the onset of gametogenesis in the roach (Rutilus rutilus): Evidence for an important role of brain-type aromatase (cyp19a1b) in the pituitary

The present study characterized changes in key parameters of reproduction in adult roach (Rutilus rutilus) from Lake Grosser Mueggelsee (Berlin, Germany) during natural gametogenesis. Fish of both sexes were sampled in monthly intervals between April and August in order to cover the onset of gametogenesis. Investigated parameters included gonad histology, plasma levels of 17β-oestradiol (E2), testosterone (T), 11-ketotestosterone (11-KT), and 17,20β-dihydroxy-4-pregnen-3-one (17,20β-P) as well as the expression of gonadotropin subunits in the pituitary. Furthermore, the mRNA-expression of brain-type aromatase (cyp19a1b), androgen receptor (ar), and estrogen receptor isoforms was studied at the pituitary level. The onset of gametogenesis - as indicated by follicles with cortical alveoli in females and first spermatogonia B in males - was observed in July, accompanied by a significant up-regulation of follicle-stimulating hormone β (fshβ) mRNA in the pituitary in both sexes. On the other hand, luteinizing hormone β (lhβ) mRNA increased later on in August. In males, the increase of fshβ mRNA in July coincided with a rise in plasma 11-KT concentrations. In females, E2 in plasma increased later, not until August, shortly before true vitellogenesis (late cortical alveoli stage). Expression of sex steroid receptors in the pituitary revealed only minor seasonal fluctuations. Most pronounced, ar mRNA displayed the highest level pre-spawning in both sexes. Interestingly, cyp19a1b mRNA-expression in the pituitary increased in parallel with fshβ already before any changes in plasma E2 or T occurred. These data suggest an important role of pituitary FSH and aromatase at the onset of gametogenesis in the roach.     

Selfish supernumerary chromosome reveals its origin as a mosaic of host genome and organellar sequences

Supernumerary B chromosomes are optional additions to the basic set of A chromosomes, and occur in all eukaryotic groups. They differ from the basic complement in morphology, pairing behavior, and inheritance and are not required for normal growth and development. The current view is that B chromosomes are parasitic elements comparable to selfish DNA, like transposons. In contrast to transposons, they are autonomously inherited independent of the host genome and have their own mechanisms of mitotic or meiotic drive. Although B chromosomes were first described a century ago, little is known about their origin and molecular makeup. The widely accepted view is that they are derived from fragments of A chromosomes and/or generated in response to interspecific hybridization. Through next-generation sequencing of sorted A and B chromosomes, we show that B chromosomes of rye are rich in gene-derived sequences, allowing us to trace their origin to fragments of A chromosomes, with the largest parts corresponding to rye chromosomes 3R and 7R. Compared with A chromosomes, B chromosomes were also found to accumulate large amounts of specific repeats and insertions of organellar DNA. The origin of rye B chromosomes occurred an estimated ～1.1-1.3 Mya, overlapping in time with the onset of the genus Secale (1.7 Mya). We propose a comprehensive model of B chromosome evolution, including its origin by recombination of several A chromosomes followed by capturing of additional A-derived and organellar sequences and amplification of B-specific repeats.     

Long-term plasticity in adult somatosensory cortex: functional reorganization after surgical removal of an arteriovenous malformation

The temporal scale of neuroplasticity following acute alterations in brain structure due to neurosurgical intervention is still under debate. We conducted a longitudinal study with the objective of investigating the postoperative changes in a patient who underwent cerebrovascular surgery and who subsequently lost proprioception in the fingers of her right hand. The results show increased activation in contralesional somatosensory areas, additional recruitment of premotor and posterior parietal areas, and changes in functional connectivity with left postcentral gyrus. These findings demonstrate long-term modifications of cortical organization and as such have important implications for treatment strategies for patients with brain injury.     

Salivary Cortisol,Salivary Alpha Amylase,and the Dental Anxiety Scale

The aim of this study was to investigate the correlation between dental anxiety, salivary cortisol, and salivary alpha amylase (sAA) levels. Furthermore, the aim was to look into individual differences such as age, race, gender, any existing pain, or traumatic dental experience and their effect on dental anxiety. This study followed a cross-sectional design and included a convenience sample of 46. Every patient was asked to complete the Dental Anxiety Scale (DAS) and a basic demographic/dental history questionnaire. A saliva sample, utilizing the method of passive drooling, was then collected in 2-mL cryovials. Samples were analyzed for salivary cortisol and sAA levels by Salimetrics. Significant associations were observed between DAS scores and presence of pain and history of traumatic dental experience. However, no significant correlations were observed between DAS, cortisol, and sAA levels. Our study reconfirms that dental anxiety is associated with presence of pain and a history of traumatic dental experience. On the other hand, our study was the first to our knowledge to test the correlation between the DAS and sAA; nevertheless, our results failed to show any significant correlation between dental anxiety, cortisol, and sAA levels.Key Words: Stress, Dental anxiety, Salivary cortisol, Salivary alpha amylase, Dental Anxiety ScaleDental anxiety is a very common phenomenon and remains an obstacle for many patients to seeking proper dental care despite all the technological advances in dentistry. Multiple etiologies have been proposed in the past. Thomson et al¹ suggested that even though endogenous factors (personality traits) play a role in its development, it develops mainly from exogenous (conditioning) factors. Van Wijk and Hoogstraten² revealed that a single early traumatic experience can be the main cause of dental anxiety. Oosterink et al³ showed that a previous traumatic experience may involve pain, negative dentist remarks (NDR), and strong negative emotional responses. As a consequence, these variables act as predictors for cancelled/missed appointments, a decrease in pain threshold with increase in patient discomfort, poor compliance, increased number of emergency appointments, jeopardized patient/dentist relationship, high Decayed Missing and Filled Teeth (DMFT) index, poor oral health perception, decreased self-esteem, and decreased oral health–related quality of life.^4–11 Women were found to be more affected than men, and there is a tendency for the younger age groups to have more anxiety.¹²Dental anxiety was found to have a direct relationship with pain perception.¹³ Rhudy and Meagher¹⁴ suggested that the pain reactivity is modulated by emotional stress. In addition, Loggia et al¹⁵ revealed changes in pain pathways on neuroimaging techniques with a negative emotional state. Furthermore, Klages et al¹⁶ revealed that anxiety increases expected or experienced pain where patients with higher anxiety levels predicted a higher pain experience.Anxiety is regarded as a form of stress and, thus, has a physiological impact on the body. Stressors can cause the activation of the autonomic nervous system (ANS), which prepares the body for the fight-or-flight reaction, and the hypothalamic-pituitary-adrenal (HPA) axis.When the autonomic nervous system (ANS) gets activated, it causes the release of epinephrine and norepinephrine from the adrenal medulla.¹⁷ Norepinephrine was shown to increase the secretion of salivary alpha amylase (sAA) from the acinar cells of the parotid and submandibular salivary glands.¹⁸ It was suggested that the level of alpha amylase in the saliva reflects the autonomic nervous system (ANS) activity and that measuring it presents an easy, noninvasive measure of ANS activity compared to measuring the actual catecholamines in serum.¹⁸ sAA levels were shown to increase in response to various stressors like exercise, cold exposure, and hypertension, in addition to psychological stress.¹⁸ Nator et al¹⁹ also demonstrated that sAA has a definite circadian rhythm wherein its levels fluctuate during the day in a definite pattern. Because the ANS is considered a rapid response, it was suggested that it may be a better measure of stress compared to measuring the hypothalamic-pituitary-adrenal axis response.^17–20Upon activation of the hypothalamic-pituitary-adrenal axis, cortisol gets secreted from the adrenal cortex to all body fluids, including saliva. It was demonstrated in the past that salivary cortisol increases in response to stress and anxiety, and that it also presents an easy, noninvasive way of measuring stress.²⁰ Cortisol levels in the saliva have been shown to be higher in patients with oral lichen planus.²¹ In addition, they were higher in patients undergoing wisdom teeth extractions and prior to urgent dental care.²² Similar to alpha amylase, cortisol has a definite circadian rhythm.The Dental Anxiety Scale (DAS), devised by Norman Corah in 1969, is the most commonly used scale to measure dental anxiety.²³ It was found to have high validity and is easy to administer; therefore, it was adopted as a measure of dental anxiety in this study.Stress and sAA associations have been well documented and studied in the literature^24–28; however, to our knowledge, no literature exists on the correlation between dental anxiety and sAA. Therefore, the aim of this study was to see if there is any correlation between dental anxiety, sAA, and salivary cortisol levels. In addition, the aim was to see if individual variations such as age, gender, race, presence of pain, or history of traumatic dental experience exhibit associations with dental anxiety. We hypothesized that dental anxiety is correlated with an increase in both alpha amylase and cortisol levels; furthermore, that presence of pain and a history of traumatic dental experience are associated with higher dental anxiety levels.     

Metastases of esophageal carcinoma to skeletal muscle: Single center experience

Metastases of esophageal carcinoma to the skeletal muscle are rare, but the incidence may be increasing because of better diagnosis resulting from widespread use of positron emission tomography/computed tomography (PET/CT). A cohort of 205 patients with esophageal carcinoma treated at our center who had PET/CT between 2006 and 2010 was retrospectively evaluated for the presence of skeletal muscle metastases. Four patients had skeletal muscle metastases of esophageal carcinoma, including two patients with squamous cell carcinoma. In another patient with squamous cell carcinoma of the esophagus and synchronous skeletal muscle metastases, muscle metastases were subsequently shown to be related to second primary pancreatic adenocarcinoma. In all cases, skeletal muscle metastases were the first manifestation of systemic disease. In three patients palliation was obtained with the combination of external beam radiation therapy, systemic chemotherapy or surgical resection. Skeletal muscle metastases are a rare complication of esophageal carcinoma.     

Minimal residual disease detectable by quantitative assessment of WT1 gene before allogeneic stem cell transplantation in patients in first remission of acute myeloid leukemia has an impact on their future prognosis

Overall 42 patients (pts) transplanted in hematological CR1 were retrospectively analyzed. Median follow‐up was 15 months (range 2–77). The expression of WT1 gene was measured according to the European Leukaemia Net recommendations. At the time of allogeneic stem cell transplantation (allo‐SCT) 29 pts were WT1‐negative and 13 pts were WT1‐positive. In the univariate analysis, significantly better results were observed in the group of WT1 neg in terms of progression‐free survival (in three yr 77% vs. 27%, p = 0.001). In multivariate analysis, the only significant feature in terms of better OS was WT1 negativity (p = 0.029). Our results show that minimal residual disease status measured by quantitative assessment of WT1 gene in acute myeloid leukemia pts in CR1 significantly affects their future prognosis after allo‐SCT.