Miracle-dz/UniFAR-FTUs huggingface dataset:
Antiinflammatory effects of long-acting beta2-agonists in patients with asthma: a systematic review and metaanalysis.

BACKGROUND Long-acting beta(2)-agonists (LABAs) are recommended as add-on therapy to antiinflammatory treatment in patients with chronic persistent asthma. Results from individual studies evaluating the in vivo antiinflammatory effect of LABAs are conflicting. The purpose of this metaanalysis was to determine whether LABAs have an in vivo antiinflammatory effect compared to placebo and whether the addition of a LABA to therapy with inhaled corticosteroids (ICSs) has a synergistic or additive antiinflammatory effect. METHODS A systematic search was performed of online databases for randomized controlled trials evaluating the antiinflammatory effects of the following: (1) LABAs compared to placebo; and (2) a LABA plus ICS vs ICS alone in adults and children with asthma. Inflammatory outcome measures included cell counts and markers of cell activation in sputum, BAL fluid, bronchial biopsy specimens, serum, and exhaled nitric oxide (ENO). Data were independently extracted by two study investigators and analyzed to generate standardized mean differences using either a fixed or random-effects metaanalysis depending on the degree of heterogeneity. RESULTS Thirty-two studies (n = 1,105 participants) met the inclusion criteria. The mean number of participants and mean number of studies for each inflammatory outcome in the metaanalysis was 113.1 (SD, 46.2) and 3.5 (SD, 1.3), respectively. There was no effect of LABA therapy on sputum, BAL fluid, or mucosal inflammatory cells in adults or in children. LABA therapy decreased ENO levels and BAL fluid albumin levels in adults. In children, LABA therapy was associated with a small decrease in serum eosinophils and interleukin-4. CONCLUSION LABA therapy does not appear to have any clinically important antiinflammatory or proinflammatory effect. LABA therapy decreases BAL fluid albumin levels, suggesting a possible modulating effect on microvascular leakage.
AT1 receptor antagonist telmisartan administered peripherally inhibits central responses to angiotensin II in conscious rats.

The effects of systemic treatment with the AT1 receptor antagonist telmisartan on central effects of angiotensin II (Ang II), namely, increase in blood pressure, vasopressin release into the circulation, and drinking response, were investigated in conscious, normotensive rats. The central responses to i.c. v. Ang II (30 ng/kg) were measured at 0.5, 2, 4, and 24 h following acute i.v. or acute and chronic oral telmisartan application. At a dose of 10 mg/kg i.v. , the drinking response to i.c. v. Ang II was completely blocked over 4 h, while the pressor response and the release of vasopressin in response to i.c. v. Ang II were blocked by 60 to 80%. The inhibition of the centrally mediated pressor and drinking response to Ang II was sustained over 24 h. The lower doses of telmisartan (0.3 and 1 mg/kg) significantly inhibited the Ang II-induced actions over 4 h. A consistent 24-h inhibition of the central responses to i.c. v. Ang II was obtained after acute and chronic oral treatment with 30 mg/kg telmisartan. Oral treatment with 1 and 3 mg/kg telmisartan produced a slight but inconsistent inhibition of the central actions of Ang II. Telmisartan concentrations measured in the cerebrospinal fluid following 8 days of consecutive daily oral treatment (1-30 mg/kg) ranged from 0.87 +/- 0.27 ng/ml (1 mg/kg/day) to 46.5 +/- 11.6 ng/ml (30 mg/kg/day). Our results demonstrate that, following peripheral administration, the AT1 receptor antagonist telmisartan can penetrate the blood-brain barrier in a dose- and time-dependent manner to inhibit centrally mediated effects of Ang II.
Hepatitis B e antigen–negative chronic hepatitis b in Hong Kong

Hepatitis B e antigen–negative chronic hepatitis B (e−CHB) has been reported in Asia but its prevalence and clinical significance have not been determined. The aims of this study were to determine the prevalence of e−CHB in Hong Kong and the frequency of precore and core promoter mutations in these patients. A cross‐sectional study was performed in 350 consecutive Chinese patients (230 men and 120 women; mean age ±SD, 42 ± 13 years) with chronic hepatitis B virus infection. A total of 243 (69%) patients were hepatitis B e antigen (HBeAg)‐negative of whom 15% had clinical cirrhosis. In the remaining 85% of patients, 63% had normal and 22% had elevated transaminases. Serum hepatitis B virus (HBV) DNA was detectable using branched DNA assay in 46% of HBeAg‐negative patients with clinical cirrhosis/elevated transaminases. Forty‐five percent of the patients with e−CHB had the precore stop codon mutation, and an additional 41% had core promoter changes. There was no correlation between the presence of precore/core promoter mutations and liver disease or HBV‐DNA levels. Overall, 17% of HBeAg‐negative patients were viremic and had evidence of chronic liver disease (e−CHB) with mean HBV‐DNA levels comparable with that in HBeAg‐positive patients. In summary, we found that e−CHB may be present in up to 17% of HBeAg‐negative patients seen in a tertiary referral center in Hong Kong. e−CHB may be a heterogenous condition and is not invariably associated with the precore HBV mutant. Population studies are needed to determine the true prevalence of e−CHB in Asia and to assess its natural course and response to treatment.
Prodrug Activation by Cryptosporidium Thymidine Kinase*

Cryptosporidium spp. cause acute gastrointestinal disease that can be fatal for immunocompromised individuals. These protozoan parasites are resistant to conventional antiparasitic chemotherapies and the currently available drugs to treat these infections are largely ineffective. Genomic studies suggest that, unlike other protozoan parasites, Cryptosporidium is incapable of de novo pyrimidine biosynthesis. Curiously, these parasites possess redundant pathways to produce dTMP, one involving thymidine kinase (TK) and the second via thymidylate synthase-dihydrofolate reductase. Here we report the expression and characterization of TK from C. parvum. Unlike other TKs, CpTK is a stable trimer in the presence and absence of substrates and the activator dCTP. Whereas the values of kcat = 0.28 s−1 and Km,ATP = 140 μm are similar to those of human TK1, the value of Km(thymidine) = 48 μm is 100-fold greater, reflecting the abundance of thymidine in the gastrointestinal tract. Surprisingly, the antiparasitic nucleosides AraT, AraC, and IDC are not substrates for CpTK, indicating that Cryptosporidium possesses another deoxynucleoside kinase. Trifluoromethyl thymidine and 5-fluorodeoxyuridine are good substrates for CpTK, and both compounds inhibit parasite growth in an in vitro model of C. parvum infection. Trifluorothymidine is also effective in a mouse model of acute disease. These observations suggest that CpTK-activated pro-drugs may be an effective strategy for treating cryptosporidiosis.
Electroreceptor development in the electric fish Eigenmannia: A histological and ultrastructural study

Developmental patterns of electroreceptors in the wealdy electric fish Eigenmannia were investigated by histological, histochemical, immunocytochemical, cell kinetic, ultrastructural, and computer‐assisted three‐dimensional reconstruction methods. The first cell of an electroreceptor primordium is embedded in the stratum germinativum of the epidermis. An unmyelinated, afferent nerve fiber ends near this cell below the basal lamina. Protrusions and vacuole‐like inclusions at the basal lamina above the nerve fiber ending suggest a mechanism of nervous induction. The receptor primordium cell subsequently divides into a single cell layer. Within 48 hours, a second apical cell layer forms from the first, and, thus, the primordium differentiates into an apical layer of presumptive receptor cells and a basal layer of presumptive supporting cells. While the two layers further differentiate into mature receptor and supporting cells, the afferent fiber penetrates the basal lamina, sprouts, and forms a synapse with each receptor cell. Transitory fibers also project along the receptor cells to the top of the developing electroreceptor but degenerate during development. Synapses are smaller in early developmental stages compared to older stages, and pre‐ and postsynaptic vesicles are more abundant and widely distributed in younger stages. Moreover, presynaptic ribbons are longer and are interconnected at their apical ends. Supporting cells continue to divide during further maturation and form new receptor cells. The number of receptor cells per tuberous organ increases during the first 4 days of electroreceptor development and plateaus when the fish are 9 days old. It declines again when organs begin to divide into clusters. © 1995 Wiley‐Liss, Inc.
The Nexus Between Price Instability and Manufacturing Growth in Nigeria (1980-2011)

The study examined the nexus between price instability and manufacturing sector growth in Nigeria between 1980 and 2011. This study adopted Error Correction model to determine the extent of the changes that took place in manufacturing output as a result of variations in exchange rate, Interest rate and Inflation rate, which are proxy for price instability. The results show that inflation rate has negatively impact on manufacturing growth in the short run while real exchange rate volatility has positive and significant effect on manufacturing growth. But the results show that in the long run that both the inflation and interest rate has positive and significant impact on manufacturing growth. The real exchange rate volatility on the other hand has negative and insignificant effect on manufacturing growth in the long run. Based on the findings of this study the government needs to place emphasis on ensuring price stability and efficiency of the manufacturing sector in order to increase the contributions of the manufacturing sector to the growth in the economy. Government must also ensure that appropriate policies are formulated and implemented so as to revive the dying manufacturing sector.
Chromosomal rearrangements directly cause underdominant F1 pollen sterility in Mimulus lewisii–Mimulus cardinalis hybrids

Chromosomal rearrangements can contribute to the evolution of postzygotic reproductive isolation directly, by disrupting meiosis in F1 hybrids, or indirectly, by suppressing recombination among genic incompatibilities. Because direct effects of rearrangements on fertility imply fitness costs during their spread, understanding the mechanism of F1 hybrid sterility is integral to reconstructing the role(s) of rearrangements in speciation. In hybrids between monkeyflowers Mimulus cardinalis and Mimulus lewisii, rearrangements contain all quantitative trait loci (QTLs) for both premating barriers and pollen sterility, suggesting that they may have facilitated speciation in this model system. We used artificial chromosome doubling and comparative mapping to test whether heterozygous rearrangements directly cause underdominant male sterility in M. lewisii–M. cardinalis hybrids. Consistent with a direct chromosomal basis for hybrid sterility, synthetic tetraploid F1s showed highly restored fertility (83.4% pollen fertility) relative to diploids F1s (36.0%). Additional mapping with Mimulus parishii–M. cardinalis and M. parishii–M. lewisii hybrids demonstrated that underdominant male sterility is caused by one M. lewisii specific and one M. cardinalis specific reciprocal translocation, but that inversions had no direct effects on fertility. We discuss the importance of translocations as causes of reproductive isolation, and consider models for how underdominant rearrangements spread and fix despite intrinsic fitness costs.
Characterization of UDP-glucuronosyltransferase genes and their possible roles in multi-insecticide resistance in Plutella xylostella (L.).

BACKGROUND Uridine diphosphate-glucuronosyltransferases (UGTs), as multifunctional detoxification enzymes, play important roles in the biotransformation of various compounds. However, their roles in insecticide resistance are still unclear. This study presents a genome-wide identification of the UGTs in diamondback moth, Plutella xylostella (L.), a notorious insect pest of cruciferous crops worldwide. The possible roles of these UGTs in insecticide resistance were evaluated. RESULTS A total of 21 putative UGTs in P. xylostella were identified. Quantitative real-time polymerase chain reaction (PCR)-based analyses showed that all the UGT genes were expressed in all tested developmental stages and tissues. Bioassay results indicated that a field-collected population (BL) was resistant to 9 of 10 commonly used insecticides, and 10 of 21 UGT mRNAs were upregulated in the BL population. Exposure to the LC50 of each insecticide affected the expression of most UGT genes. Among these, the expression levels of UGT40V1, UGT45B1 and UGT33AA4 were induced by more than five insecticides, whereas indoxacarb and metaflumizone significantly repressed the expression of most UGT genes. CONCLUSION UGTs may play important roles in the metabolism of commonly used insecticides in P. xylostella. These findings provide valuable information for further research on the physiological and toxicological functions of specific UGT genes in P. xylostella. © 2017 Society of Chemical Industry.
Changing incidence of mycobacterial diseases in German patients with HIV infection.

Before the introduction of potent antiretroviral therapy, disease caused by atypical mycobacteria was a frequent diagnosis in patients with fewer than 100 CD4+ cells/microL and could affect virtually every organ. The diagnosis was associated with a survival of usually less than 1 year, and antimycobacterial treatment could extend the life span by only several months. However, the clinical face of the HIV epidemic has changed profoundly since 1996, most probably due ot the antiretroviral combination strategies. In this discussion, we assess the influence of the introduction of antiretroviral combination therapies on the incidence of mycobacterial infections from 1994 to 1998 in a cohort of German HIV-seropositive patients treated at an HIV outpatient clinic.
Localization of tyrosine hydroxylase and its messenger RNA in the brain of rainbow trout by immunocytochemistry and in situ hybridization

This report describes the distribution of tyrosine hydroxylase (TH)‐expressing structures in the brain of rainbow trout (Oncorhynchus mykiss). TH neurons have been localized by the use of two complementary techniques, immunocytochemistry and in situ hybridization of TH messenger RNA. Results obtained from in situ hybridization and immunocytochemistry were in agreement. TH cells were observed in many areas of the brain, with a higher density at the level of the olfactory bulbs where TH‐positive neurons are abundant in the internal cell layer. In the telencephalon, two populations of TH neurons can be distinguished: one group is located in the area ventralis telencephali pars dorsalis, and the other group is located in the area ventralis telencephali pars ventralis and extends laterally in the area ventralis telencephali pars lateralis. Many labeled neurons are also seen in the preoptic area as well as in the hypothalamus, where several clusters of TH‐positive cells are observed. Some of these neurons located in the paraventricular organ grow a short cytoplasmic extension directed to the ventricular wall and are known to be cerebrospinal fluid‐contacting cells. The most caudal TH neurons are observed at the level of the locus caeruleus. At the level of the pituitary, TH‐positive fibers are observed in the neurohypophysis. The TH‐immunoreactive innervation at the level of the pituitary provides a neuroanatomic basis for the effects of dopamine and/or norepinephrine on the release of pituitary hormones in fish. J. Comp. Neurol. 449:374–389, 2002. © 2002 Wiley‐Liss, Inc.
Effects of oxidation and cytosolic redox conditions on excitation–contraction coupling in rat skeletal muscle

In this study the effects of oxidation and reduction on various steps in the excitation‐contraction (E–C) coupling sequence was examined in mammalian skeletal muscle. In mechanically skinned fast‐twitch fibres, electric field stimulation was used to generate action potentials in the sealed transverse‐tubular (T‐) system, thereby eliciting twitch responses, which are a sensitive measure of Ca2+ release. Treatment of fibres with the oxidant H2O2 (200 μm and 10 mm) for 2–5 min markedly potentiated caffeine‐induced Ca2+ release and the force response to partial depolarisation of the T‐system (by solution substitution). Importantly, such H2O2 treatment had no effect at all on any aspect of the twitch response (peak amplitude, rate of rise, decay rate constant and half‐width), except in cases where it interfered with the T‐system potential or voltage‐sensor activation, resulting in a reduction or abolition of the twitch response. Exposure to strong thiol reductants, dithiothreitol (DTT, 10 mm) and reduced glutathione (GSH, 5 mm), did not affect the twitch response over 5 min, nor did varying the glutathione ratio (reduced to oxidised glutathione) from the level present endogenously in the cytosol of a rested fibre (30:1) to the comparatively oxidised level of 3:1. In fibres that had been oxidised by H2O2 (10 mm) (or by 2,2′‐dithiodipyridine, 100 μm), exposure to GSH (5 mm) caused potentiation of twitch force (by ∼20 % for H2O2); this effect was due to the increase in the Ca2+ sensitivity of the contractile apparatus that occurs under such circumstances and was fully reversed by subsequent exposure to 10 mm DTT. We conclude that: (a) the redox potential across the sarcomplamsic reticulum has no noticeable direct effect on normal E–C coupling in mammalian skeletal muscle, (b) oxidising the Ca2+‐release channels and greatly increasing their sensitivity to Ca2+‐induced Ca2+ release does not alter the amount of Ca2+ released by an action potential and (c) oxidation potentiates twitches by a GSH‐mediated increase in the Ca2+ sensitivity of the contractile apparatus.
Primary thrombophilia in Mexico. V. A comprehensive prospective study indicates that most cases are multifactorial

Over a 36‐month period, 46 consecutive Mexican mestizos with a clinical marker associated with a primary hypercoagulable state were prospectively assessed by searching for the sticky platelet syndrome (SPS), the activated protein C resistance (aPCR) phenotype, coagulation protein C activity and antigen, coagulation protein S, antithrombin III, plasminogen, tissue‐type plasminogen activator activity, plasminogen activator inhibitor activity, plasminogen activator inhibitor type 1, IgG and IgM isotypes of antiphospholipid antibodies, homocysteine levels, the factor V gene Leiden, Cambridge, Hong Kong, and Liverpool mutations, the 677 C→T mutation in the 5,10‐methylenetetrahydrofolatereductase (MTHFR), and the G20210A polymorphism in the 3′‐untranslated region of the prothrombin gene. Of the 46 consecutive patients prospectively accrued in the study, only 12 (26%) were males, the median age being 38 years (range 10–63 years). In only four individuals (8%) could we not record any abnormality. In 5/42 patients with abnormal results (12%), a single abnormality was recorded, whereas in the remaining 37, two to five co‐existing abnormalities were identified. We found 22 (48%) patients with the SPS, 11 (24%) with the aPCR phenotype, 5 (11%) with the factor V Leiden mutation, 7 (15%) with the prothrombin gene mutation, 29 (63%) with the MTHFR gene mutation, 11 (24%) with the factor V HR2 haplotype, 11 (24%) with antiphospholipid antibodies, 4 (9%) with PS deficiency, 6 (13%) with PC deficiency, one with the FV Hong Kong mutation, and one with AT‐III deficiency. The results are consonant with the idea that most cases of thrombophilia in Mexico are multifactorial. Am. J. Hematol. 78:21–26, 2005. © 2004 Wiley‐Liss, Inc.
Do Discriminatory Leniency Policies Fight Hard‐Core Cartels?

This paper experimentally analyzes the effects of nondiscriminatory and discriminatory leniency policies on hard‐core cartels. We design a mechanism to form a hard‐core cartel, which allows that multiple ringleaders emerge. Ringleaders often take a leading role in the coordination and formation of hard‐core cartels. A leniency policy that grants amnesty to all “whistle‐blowers” except for ringleaders may therefore reduce the incentive to become a ringleader and disrupt cartel formation. Yet, our experimental results show that whistle‐blowing rarely occurs. Paradoxically, the discriminatory leniency policy induces firms to become ringleaders. We find that firms create trust among other firms when acting as ringleaders. This signaling effect ultimately facilitates coordination in the explicit cartel.
Mineral Metabolism and Bone Mass at Peripheral and Axial Skeleton in Diabetes Mellitus

Bone mineral content (BMC), mineral homeostasis, and diabetes control were evaluated in 31 Caucasian insulin-dependent diabetic patients (disease duration 18.3 ± 7.7 yr, mean ± SD) with normal kidney function. To evaluate bone mass, we performed radiogrammetry and single- and dual-photon absorptiometry. In women, a significantly lower mean BMC was found in the distal radius, at a mixed trabecular-cortical (P < .01) and a cortical (P < .05) site, as well as in the lumbar spine (P < .02). In diabetic men, mean BMC was significantly reduced at the trabecularcortical (P < .01) and cortical (P < .05) sites of the radius but not in the lumbar spine. When expressed as densities (i.e., BMC/width or lumbar BMC/area), only the BMC/width at the radius cortical area was significantly reduced in women (P < .05). The results of the radiogrammetry showed a larger endosteal diameter in the diabetic women, resulting in a significantly lower cortical thickness (P < .05). Diabetic men did not show abnormalities on radiogrammetry. Diabetic patients had diminished serum calcium and phosphorus concentrations (P < .001), whereas serum parathyroid, 25-hydroxyvitamin D3, and concentrations of both total and free 1,25-dihydroxyvitamin D3 were normal. No correlation between parameters of diabetes control (HbA1, insulin dose, and triglycerides) or calcium-regulating hormones and BMC were found. These data confirm that, despite large overlap of individual values, mean bone mass at the peripheral skeleton is significantly decreased in diabetic patients. Moreover, we report that the BMC of the lumbar spine is significantly reduced in female diabetic patients.