Miracle-dz/UniFAR-FTUs huggingface dataset:
Epidemiology of Opisthorchis viverrini infection in a rural district of southern Lao PDR

Objective: to describe epidemiological features of O. viverrini infection in a highly endemic district. Methods: A random sample of 13 villages and 15 randomly selected households per village was investigated. All household members older than 6 months were included. Each study participant underwent a short clinical examination and was interviewed on behaviour and nutritional risk factors. A stool sample was examined using Kato-Katz technique. Fish samples in each village were dissected for the presence of meta-cercariae. Results: 814 persons were enrolled. 51.5% were women. Median age was 16 years. 58.5% were infected with O. viverrini. Infection rates were similar between sex but increased by age from 20.0% in children below 6 years to 85.5% in adults between 45 and 55 years of age (p<0.001). Intensity of infection and the habit to consume raw or insufficiently cooked fish increased with age, too. 75.2% of the study participants reported to consume raw or insufficiently cooked fish. Multiple helminth infections were frequent. 23 different species of cyprinoid fish are consumed in the study villages of whom 20 species were infected with meta-cercariae. At village level the prevalence of raw fish consumption was strongly associated with infection rate (r=0.76, p=0.003). Only in one village latrines were available in the household. 95.0% of the study participants reported to defecate in the forest. A logistic regression model identified age, the consumption of raw or insufficiently cooked fish and absence of sanitation as main risk factors at individual level. Conclusion: The study documents highly prevalent for O. viverrini infection and transmission indicators. Community interventions are urgently needed.
A DEAD-box RNA helicase promotes thermodynamic equilibration of kinetically trapped RNA structures in vivo

RNAs must assemble into specific structures in order to carry out their biological functions, but in vitro RNA folding reactions produce multiple misfolded structures that fail to exchange with functional structures on biological time scales. We used carefully designed self-cleaving mRNAs that assemble through well-defined folding pathways to identify factors that differentiate intracellular and in vitro folding reactions. Our previous work showed that simple base-paired RNA helices form and dissociate with the same rate and equilibrium constants in vivo and in vitro. However, exchange between adjacent secondary structures occurs much faster in vivo, enabling RNAs to quickly adopt structures with the lowest free energy. We have now used this approach to probe the effects of an extensively characterized DEAD-box RNA helicase, Mss116p, on a series of well-defined RNA folding steps in yeast. Mss116p overexpression had no detectable effect on helix formation or dissociation kinetics or on the stability of interdomain tertiary interactions, consistent with previous evidence that intracellular factors do not affect these folding parameters. However, Mss116p overexpression did accelerate exchange between adjacent helices. The nonprocessive nature of RNA duplex unwinding by DEAD-box RNA helicases is consistent with a branch migration mechanism in which Mss116p lowers barriers to exchange between otherwise stable helices by the melting and annealing of one or two base pairs at interhelical junctions. These results suggest that the helicase activity of DEAD-box proteins like Mss116p distinguish intracellular RNA folding pathways from nonproductive RNA folding reactions in vitro and allow RNA structures to overcome kinetic barriers to thermodynamic equilibration in vivo.
Decreased CSF-beta-amyloid 42 in Alzheimer's disease and amyotrophic lateral sclerosis may reflect mismetabolism of beta-amyloid induced by disparate mechanisms.

Both tau and beta-amyloid 42 (Abeta42) have been implicated in Alzheimer's disease (AD) and tau alone in frontotemporal dementia (FTD) and amyotrophic lateral sclerosis (ALS). These proteins can be measured in the cerebrospinal fluid (CSF); differences from normal CSF levels may reflect pathophysiological mechanisms. Using ELISAs, we investigated the levels of total CSF-tau (here referred to as tau), phosphorylated CSF-tau (phosphotau), and Abeta42 in patients with AD (n = 19), FTD (n = 14), ALS (n = 11) and Parkinson's disease (PD; n = 15) and in age-matched controls (n = 17). Both CSF-tau and CSF-phosphotau were increased in AD compared with FTD (p < 0.001), ALS (p < 0.001), PD (p < 0.001) and controls (p < 0.001). CSF-Abeta42 was markedly decreased in AD and ALS (both p < 0.001) and slightly decreased in FTD (p < 0.01) and PD (p < 0.05) compared with controls. Using CSF-phosphotau may improve the differentiation of AD from FTD and ALS in clinical praxis. Furthermore, decreased CSF-Abeta42 levels may be common in neurodegenerative disorders possibly reflecting changes in the metabolism of beta-amyloid or axonal degeneration.
WT1 MUTATION IN MALIGNANT MESOTHELIOMA AND WT1 IMMUNOREACTIVITY IN RELATION TO p53 AND GROWTH FACTOR RECEPTOR EXPRESSION, CELL‐TYPE TRANSITION, AND PROGNOSIS

The Wilms tumour 1 (WT1) gene is believed to contribute to the growth and differentiation of certain tissues, including mesothelium. This study assessed WT1 gene status by mutational screening in 42 malignant mesotheliomas (MMs) and 3 MM cell lines and detected two tumours with identical heterozygous single nucleotide deletions in intron 7, with no apparent consequence for WT1 function. Furthermore, the expression pattern of the WT1 gene was studied in MMs and related lesions using three anti‐WT1 monoclonal antibodies (MAbs). Strong to moderate nuclear immunoreactivity was noted in MM in situ (54/56), cultured mesothelioma cells (4/5), and hyperplastic and normal pleural (non‐neoplastic, NNM) specimens. WT1 immunoreactivity was absent in all primary tumours of lung and in pleural metastases from adenocarcinomas of breast and colon; immunoreactivity was present in pleural metastases from renal carcinomas, melanomas, and papillary carcinomas of the ovary. Expression of the WT1 protein in MM was not correlated with survival. Coordinate expression of the WT1 protein and its putative transcriptional target genes was determined by correlating WT1 immunostaining with epidermal growth factor receptor (EGF‐R) and insulin‐like growth factor 1 receptor (IGF‐1R) expression on MM and NNM; no significant correlation was found, irrespective of p53 expression status. Finally, the putative involvement of WT1 in cell‐type transition was supported by this study, in that epithelial mesothelioma showed the strongest WT1 immunoreactivity while sarcomatous mesothelioma showed the least. © 1997 by John Wiley & Sons, Ltd.
Some observations on the biting behavior of Anopheles gambiae s.s., Anopheles arabiensis, and Anopheles funestus and their implications for malaria control.

Studies were carried out in three villages in western Kenya on the biting behavior of Anopheles gambiae s.s. , Anopheles arabiensis, and Anopheles funestus. Blood feeding behavior and departure from houses were studied under the impact of permethrin-impregnated eaves-sisal curtains. Only 2-13% of the female vector population was collected biting before 2200 hr. Over 90% of the villagers went to bed by 2100 hr. An. funestus was 6.6-8.2 times more likely to bite people indoors than outdoors, while An. gambiae s.l. females were only 2 times as likely. Under the influence of permethrin-impregnated sisal curtains placed under the eaves of village houses, there was a marked egress of blood-fed An. funestus and An. gambiae s.s. Permethrin seems to have induced exophily of half-gravid female An. gambiae s.s. While An. gambiae s.s. remained highly anthropophagic under the impact of permethrin, An. funestus shifted to feeding more on cattle. An arabiensis were largely zoophilic. Our results underline the difficulties of controlling An. gambiae s.s. , the principal African malaria vector. New strategies must be found to control this vector.
Low‐intensity training dissociates metabolic from aerobic fitness

This study investigated the effect of prolonged whole‐body low‐intensity exercise on blood lipids, skeletal muscle adaptations and aerobic fitness. Seven male subjects completed a 32‐day crossing of the Greenland icecap on cross‐country skies and before and after this arm or leg cranking was performed on two separate days and biopsies were obtained from arm and leg muscle, and venous blood was sampled.
The therapeutic effect of a new ultra low concentration estriol gel formulation (0.005% estriol vaginal gel) on symptoms and signs of postmenopausal vaginal atrophy: results from a pivotal phase III study

Objective The aim of this study was to evaluate the efficacy and safety of a new low-concentration estriol formulation (0.005% estriol vaginal gel), providing an ultra low dose of estriol per application (50 &mgr;g), for the local treatment of postmenopausal vaginal atrophy. Methods Postmenopausal women with symptoms and signs of vaginal atrophy were enrolled in a prospective, double-blind, placebo-controlled study. Women received either 1 g of vaginal gel containing 50 &mgr;g of estriol or placebo gel, daily for 3 weeks and then twice weekly up to 12 weeks. A cytological vaginal study, evaluation of vaginal pH, and assessment of symptoms and signs of vaginal atrophy were performed, and changes between baseline and weeks 3 and 12 were assessed. Adverse events were recorded. Results A total of 167 women were included (114 received estriol and 53 received placebo). After 12 weeks of therapy, a superiority of estriol compared with placebo gel was shown in the change in maturation value and vaginal pH (P < 0.001 and P < 0.001, respectively). The superiority of estriol was well demonstrated in improvement of vaginal dryness (P = 0.001) and the Global Symptom Score (P = 0.018). Estriol gel proved also superior in the improvement of several of the most outstanding vaginal signs of vaginal atrophy evaluated. After 3 weeks, estriol gel also showed a superiority over the placebo gel in most symptoms and signs evaluated. Treatment-related adverse events were similar among groups. Conclusions 0.005% Estriol vaginal gel, a new formulation providing an ultra low dose of estriol per application, was shown to be safe and effective in the treatment of postmenopausal vaginal atrophy.
Thyroid hormone suppresses the differentiation of osteoprogenitor cells to osteoblasts, but enhances functional activities of mature osteoblasts in cultured rat calvaria cells

The effects of thyroid hormone on osteoblastic differentiation and activity were studied in fetal rat calvaria (RC) cells cultured for up to 30 days in medium supplemented with thyroid hormone‐depleted serum. In this condition, the cells proliferated and differentiated to form mineralized bone nodules (BN) and expressed osteoblastic markers such as alkaline phosphatase (ALP), osteocalcin (OCN), and osteopontin (OPN). The continuous presence of triiodothyronine (T3) at 10‐9‐10‐8 M in the medium inhibited the osteoblastic differentiation: 34% decrease in ALP activity on day 12 and 60% decrease in BN formation on day 15 at 10‐8 M. T3 at these doses had no effect on the DNA content of RC cells at confluence (day 6). Short‐term (48‐h) exposure of T3 at 10‐9 M or higher decreased ALP activity when RC cells were differentiating (days 7–11). However, when BN formation by the cells had already reached a plateau (day 28), the activity was increased by treatment with T3 at 10‐7‐10‐6 M. OCN production was increased dose dependently by this treatment with T3 (2.1‐fold and 1.3‐fold of control at 10‐8 M on days 11 and 28, respectively). Similar increases were observed in the levels of OCN mRNA. In addition, increases in phosphorylated OPN in the medium (day 11) and mineralized matrix (day 28) were observed (1.5‐fold at 10‐8‐10‐6 M), while OPN synthesis and the level of its mRNA were depressed by T3 (60‐70% of control at 10‐8 M). These results suggest that T3 regulates osteoblastic differentiation and activity depending on the state of cell differentiation: T3 suppresses the differentiation of osteoprogenitor cells to osteoblasts, but enhances the functional activity of mature osteoblasts. © 1994 Wiley‐Liss, Inc.
Nav1.5 N-terminal domain binding to α1-syntrophin increases membrane density of human Kir2.1, Kir2.2 and Nav1.5 channels.

AIMS Cardiac excitability and refractoriness are largely determined by the function and number of inward rectifier K⁺ channels (Kir2.1-2.3), which are differentially expressed in the atria and ventricles, and Nav1.5 channels. We have focused on how Nav1.5 and Kir2.x function within a macromolecular complex by elucidating the molecular determinants that govern Nav1.5/Kir2.x reciprocal modulation. METHODS AND RESULTS The results demonstrate that there is an unexpected 'internal' PDZ-like binding domain located at the N-terminus of the Nav1.5 channel that mediates its binding to α1-syntrophin. Nav1.5 N-terminal domain, by itself (the 132 aa peptide) (Nter), exerts a 'chaperone-like' effect that increases sodium (I(Na)) and inward rectifier potassium (I(K1)) currents by enhancing the expression of Nav1.5, Kir2.1, and Kir2.2 channels as demonstrated in Chinese hamster ovary (CHO) cells and in rat cardiomyocytes. Site-directed mutagenesis analysis demonstrates that the Nter chaperone-like effect is determined by Serine 20. Nav1.5-Kir2.x reciprocal positive interactions depend on a specific C-terminal PDZ-binding domain sequence (SEI), which is present in Kir2.1 and Kir2.2 channels but not in Kir2.3. Therefore, in human atrial myocytes, the presence of Kir2.3 isoforms precludes reciprocal I(K1)-INa density modulation. Moreover, results in rat and human atrial myocytes demonstrate that binding to α1-syntrophin is necessary for the Nav1.5-Kir2.x-positive reciprocal modulation. CONCLUSIONS The results demonstrate the critical role of the N-terminal domain of Nav1.5 channels in Nav1.5-Kir2.x-reciprocal interactions and suggest that the molecular mechanisms controlling atrial and ventricular cellular excitability may be different.
1-Methylguanosine deficiency of tRNA influences cognate codon interaction and metabolism in Salmonella typhimurium

1-Methylguanosine (m1G) is present next to the 3' end of the anticodon (position 37) in tRNA(1,2,3,Leu), tRNA(1,2,3,Pro), and tRNA(3Arg). A mutant of Salmonella typhimurium lacks m1G in these seven tRNAs when grown at or above 37 degrees C, as a result of a mutation (trmD3) in the structural gene (trmD) for the tRNA(m1G37)methyltransferase. The m1G deficiency induced 24 and 26% reductions in the growth rate and polypeptide chain elongation rate, respectively, in morpholinepropanesulfonic acid (MOPS)-glucose minimal medium at 37 degrees C. The expression of the leuABCD operon is controlled by the rate with which tRNA(2Leu) and tRNA(3Leu) read four leucine codons in the leu-leader mRNA. Lack of m1G in these tRNAs did not influence the expression of this operon, suggesting that m1G did not influence the efficiency of tRNA(2,3Leu). Since the average step time of the m1G-deficient tRNAs was increased 3.3-fold, the results suggest that the impact of m1G in decoding cognate codons may be tRNA dependent. The trmD3 mutation rendered the cell more resistant or sensitive to several amino acid analogs. 3-Nitro-L-tyrosine (NT), to which the trmD3 mutant is sensitive, was shown to be transported by the tryptophan-specific permease, and mutations in this gene (mtr) render the cell resistant to NT. Since the trmD3 mutation did not affect the activity of the permease, some internal metabolic step(s), but not the uptake of the analog per se, is affected. We suggest that the trmD3-mediated NT sensitivity is by an abnormal translation of some mRNA(s) whose product(s) is involved in the metabolic reactions affected by the analog. Our results also suggest that tRNA modification may be a regulatory device for gene expression.
Nandrolone decanoate enhances hypothalamic biogenic amines in rats.

PURPOSE To identify possible mechanisms for an anabolic-androgenic steroid induced increase in aggressive behavior and work capacity, the levels of some biogenic amines considered to be closely related to a systemic hyper-adrenergic state were measured in selected regions of the brain. METHODS Wistar male rats were divided randomly into five groups: nontreated (control), oil-vehicle-treated (vehicle) or one of three (therapeutic dose and 10- or 100-fold higher dose) anabolic-androgenic steroid-treated (steroid-1, -2, -3) groups. Rats in the steroid and vehicle groups were given a single dose of nandrolone decanoate or oil vehicle, respectively, one week before tissue sampling. The levels of norepinephrine (NE) and its metabolite, 4-hydroxy-3-methoxyphenylglycol (MHPG), serotonin (5-HT) and its metabolite, 5-hydroxy-indole-3-acetic acid (5-HIAA) were measured in the cerebral cortex, hypothalamus and cerebellum by high-performance liquid chromatography. Immunostaining for c-fos was performed as a confirmation of increased neural activity. RESULTS The levels of NE and MHPG were increased by approximately 2- and approximately 7-fold in the hypothalamus of the steroid-2 compared with the control and vehicle groups. The levels of 5-HT and 5-HIAA were approximately 40 and approximately 50% higher in the steroid-2 compared with the control and vehicle groups. A significantly higher number of c-fos expressing neurons were observed in the periventricular region of the steroid-2 than the control and vehicle groups, indicating enhanced neuronal activity after nandrolone decanoate treatment. CONCLUSIONS The present results, combined with previously reported findings of physical performance enhancement after anabolic-androgenic steroid treatment, are consistent with the interpretation that elevated levels of adrenergic and serotonergic amines in the hypothalamus could contribute to aggressive behaviors as well as improved physical performance.
Functional interdependence of neurons in a single canine intrinsic cardiac ganglionated plexus

1 To determine the activity characteristics displayed by different subpopulations of neurons in a single intrinsic cardiac ganglionated plexus, the behaviour and co‐ordination of activity generated by neurons in two loci of the right atrial ganglionated plexus (RAGP) were evaluated in 16 anaesthetized dogs during basal states as well as in response to increasing inputs from ventricular sensory neurites. 2 These sub‐populations of right atrial neurons received afferent inputs from sensory neurites in both ventricles that were responsive to local mechanical stimuli and the nitric oxide donor nitroprusside. Neurons in at least one RAGP locus were activated by epicardial application of veratridine, bradykinin, the β1‐adrenoceptor agonist prenaterol or glutamate. Epicardial application of angiotensin II, the selective β2‐adrenoceptor agonist terbutaline and selective α‐adrenoceptor agonists elicited inconsistent neuronal responses. 3 The activity generated by both populations of atrial neurons studied over 5 min periods during basal states displayed periodic coupled behaviour (cross‐correlation coefficients of activities that reached, on average, 0·88 ± 0·03; range 0·71–1) for 15–30 s periods of time. These periods of coupled activity occurred every 30–50 s during basal states, as well as when neuronal activity was enhanced by chemical activation of their ventricular sensory inputs. 4 These results indicate that neurons throughout one intrinsic cardiac ganglionated plexus receive inputs from mechano‐ and chemosensory neurites located in both ventricles. That such neurons respond to multiple chemical stimuli, including those liberated from adjacent adrenergic efferent nerve terminals, indicates the complexity of the integrative processing of information that occurs within the intrinsic cardiac nervous system. 5 It is proposed that the interdependent activity displayed by populations of neurons in different regions of one intrinsic cardiac ganglionated plexus, responding as they do to multiple cardiac sensory inputs, forms the basis for integrated regional cardiac control.
Significantly higher adrenocorticotropin-stimulated cortisol and 17-hydroxyprogesterone levels in 337 consecutive, premenopausal, caucasian, hirsute patients compared with healthy controls.

OBJECTIVE To investigate whether elevated ACTH-stimulated 17-hydroxyprogesterone (17OHP) levels are caused by CYP21 genetic defects or by a general adrenal hyperresponsiveness in hirsute patients. METHODS A total of 337 hirsute patients were evaluated by Ferriman-Gallwey score, serum testosterone, ACTH-stimulated 17OHP, and cortisol during the follicular phase. A cutoff value of 16 nmol/liter for maximum ACTH-stimulated 17OHP (M17OHP) responses was defined as the upper limit of the 95% confidence interval (CI) for the 97.5 percentile in 42 female controls. All patients were offered total screening of the CYP21 gene, and 252 healthy, premenopausal women with regular menses underwent genetic screening. RESULTS Patients were divided into idiopathic hirsutism (IH) (n = 180) and polycystic ovary syndrome (PCOS) (n = 157) groups. M17OHP levels were significantly higher in IH [geometric mean value (nmol/liter +/- 2 sd) 12.2 (4.6-32.3)] and PCOS [11.9 (5.3-27.2)] compared with controls [8.5 (5.1-14.2)] (P < 0.001). A similar percentage of IH and PCOS patients had elevated M17OHP (20.5 vs. 20.8%, not significant), and these also had significantly higher 30-min cortisol levels compared with controls (P < 0.05). The prevalence of CYP21 mutations in patients was 8.6% compared with 6.3% in controls (P = 0.38). Ten of 19 carriers had M17OHP levels below the cutoff limit. CONCLUSION The significantly higher ACTH-stimulated levels of cortisol and 17OHP in hirsute patients indicated adrenal hyperresponsiveness in IH and PCOS. CYP21-carrier status could not explain the observed high prevalence of abnormal ACTH-stimulated 17OHP levels in the hirsute population.
Evaluation of Kato thick-smear technique for quantitative diagnosis of helminth infections.

Summary A method of fecal examination described by Kato and involving the clearing of a direct fecal smear pressed thin under a glycerin-impregnated cellophane coverslip was evaluated for possible use in quantitative diagnosis of helminth infections. Modifications were described for 1) removing fiber from the fecal sample, 2) uniformly spreading the smear, and 3) preventing over-clearing of the preparation. Optimum time for clearing the smears was found to be about 30 minutes at 35°C, or about 1 hour under openroom conditions. The thick-smear method was found to be as sensitive as the Bell filtration, zine-surface flotation, and Hoffman sedimentation methods of concentration of feces. Egg-counts for estimation of intestinal nematode and Schistosoma mansoni infections were as reproducible when made by the thick-smear method as by dilution or concentration procedures. Series of egg-counts made from the same stool and from daily stools indicated that eggs of S. mansoni, as well as those of other worms, are distributed randomly in the feces and are in equal numbers in the outer and inner portions of the stool. Thus egg-counts made by the thick-smear technique appear to be reliable for the quantitative diagnosis of helminth infect ons.