Ovarian production of progesterone and 20 alpha-dihydroprogesterone in vitro following prostaglandin F2 alpha induced luteolysis in the superluteinized rat.
Superluteinized rats were injected with the prostaglandin F2 alpha (PGF2 alpha) analogue cloprostenol to induce luteolysis. The treatment decreased progesterone production of ovarian homogenates from 8.9 +/- 0.5 to 4.0 +/- 0.7 nmol/ovary/10 min (mean +/- SEM) within 40 min. tochondrial fractions isolated from control and cloprostenol treated animals produced 4.7 +/- 0.4 and 2.8 +/- 0.3 nmol progesterone/ovary/10 min, respectively. Thus, the PGF2 alpha analogue treatment significantly reduced mitochondrial progesterone production. Addition of the 15 000 X g supernatant fraction did not influence the progesterone production rates of the mitochondrial fraction. The basal progesterone secretion from quartered ovaries decreased from 1.50 +/- 0.15 to 0.38 +/- 0.05 nmol/ovary during the initial 15 min of incubation following cloprostenol administration. hCG and N6,O2'-dibutyryladenosine 3':5'-cyclic monophosphate (DBC) stimulated the progesterone secretion from quartered ovaries, but the response was delayed in ovaries obtained from cloprostenol treated animals. Although the response was delayed, the progesterone secretion following cloprostenol treatment was re-activated with cAMP either directly or via hCG. The increment in progesterone secretion above unstimulated controls in response to DBC was not influenced by the cloprostenol treatment while the increment caused by hCG was decreased. Our data suggest that: 1) PGF2 alpha deactivates mitochondrial progesterone production, 2) this deactivation may be overcome by cAMP, and 3) PGF2 alpha decreases gonadotrophin responsive adenylyl cyclase.


Smoking and peptic ulcer in rheumatoid arthritis.
The prevalence of chronic peptic ulcer among 152 out-patients with rheumatoid arthritis attending a district general hospital was found to be 16.4% (25 patients), as against 6.6% (10 patients) among an equal number of matched control out-patients with other diagnoses. There was no evidence that any form of anti-inflammatory treatment increased ulcer risk, but smoking was significantly associated with a higher prevalence of ulcer. This relationship was shown to be quantitative and to depend upon an increased frequency of duodenal ulcer in women who smoked. It is possible that greater numbers would have shown the effect of smoking to apply to both sexes, and that for all patients with rheumatoid arthritis abstention from smoking could diminish the high risk of peptic ulceration associated with this disease.


GIGN: Learning Graph-in-graph Representations of EEG Signals for Continuous Emotion Recognition.
Effectively learning the spatial topology information of EEG channels as well as the temporal contextual information underlying emotions is crucial for EEG emotion regression tasks. In this paper, we represent EEG signals as spatial graphs in a temporal graph (SGTG). A graph-in-graph neural network (GIGN) is proposed to learn the spatial-temporal information from the proposed SGTG for continuous EEG emotion recognition. A spatial graph neural network (GCN) with a learnable adjacency matrix is utilized to capture the dynamical relations among EEG channels. To learn the temporal contextual information, we propose to use GCN to combine the short-time emotional states of each spatial graph embeddings with the help of a learnable adjacency matrix. Experiments on a public dataset, MAHNOB-HCI, show the proposed GIGN achieves better regression results than recently published methods for the same task. The code of GIGN is available at: https://github.com/yi-ding-cs/GIGN.


Recent developments and applications of ambient mass spectrometry imaging in pharmaceutical research: an overview.
The application of ambient mass spectrometry imaging "MSI" is expanding in the areas of fundamental research on drug delivery and multiple phases of the process of identifying and developing drugs. Precise monitoring of a drug's pharmacological workflows, such as intake, distribution, metabolism, and discharge, is made easier by MSI's ability to determine the concentrations of the initiating drug and its metabolites across dosed samples without losing spatial data. Lipids, glycans, and proteins are just a few of the many phenotypes that MSI may be used to concurrently examine. Each of these substances has a particular distribution pattern and biological function throughout the body. MSI offers the perfect analytical tool for examining a drug's pharmacological features, especially in vitro and in vivo effectiveness, security, probable toxic effects, and putative molecular pathways, because of its high responsiveness in chemical and physical environments. The utilization of MSI in the field of pharmacy has further extended from the traditional tissue examination to the early stages of drug discovery and development, including examining the structure-function connection, high-throughput capabilities in vitro examination, and ex vivo research on individual cells or tumor spheroids. Additionally, an enormous array of endogenous substances that may function as tissue diagnostics can be scanned simultaneously, giving the specimen a highly thorough characterization. Ambient MSI techniques are soft enough to allow for easy examination of the native sample to gather data on exterior chemical compositions. This paper provides a scientific and methodological overview of ambient MSI utilization in research on pharmaceuticals.


Advances in the chemistry of small molecule fluorescent probes.
Small molecule fluorophores are essential tools for chemical biology. A benefit of synthetic dyes is the ability to employ chemical approaches to control the properties and direct the position of the fluorophore. Applying modern synthetic organic chemistry strategies enables efficient tailoring of the chemical structure to obtain probes for specific biological experiments. Chemistry can also be used to activate fluorophores; new fluorogenic enzyme substrates and photoactivatable compounds with improved properties have been prepared that facilitate advanced imaging experiments with low background fluorescence. Finally, chemical reactions in live cells can be used to direct the spatial distribution of the fluorophore, allowing labeling of defined cellular regions with synthetic dyes.


Long-range transcriptome sequencing reveals cancer cell growth regulatory chimeric mRNA.
mRNA chimeras from chromosomal translocations often play a role as transforming oncogenes. However, cancer transcriptomes also contain mRNA chimeras that may play a role in tumor development, which arise as transcriptional or post-transcriptional events. To identify such chimeras, we developed a deterministic screening strategy for long-range sequence analysis. High-throughput, long-read sequencing was then performed on cDNA libraries from major tumor histotypes and corresponding normal tissues. These analyses led to the identification of 378 chimeras, with an unexpectedly high frequency of expression (≈2 x 10(-5) of all mRNA). Functional assays in breast and ovarian cancer cell lines showed that a large fraction of mRNA chimeras regulates cell replication. Strikingly, chimeras were shown to include both positive and negative regulators of cell growth, which functioned as such in a cell-type-specific manner. Replication-controlling chimeras were found to be expressed by most cancers from breast, ovary, colon, uterus, kidney, lung, and stomach, suggesting a widespread role in tumor development.


Molecular mechanisms of altered cholesterol metabolism in rats with spontaneous focal glomerulosclerosis.
Imai rats exhibit spontaneous focal glomerulosclerosis (FGS), which is marked by heavy proteinuria, severe hyperlipidemia, and progressive renal insufficiency beginning at 8 to 10 weeks of age. In an earlier study, we reported severe skeletal muscle and adipose tissue lipoprotein lipase, and very low-density lipoprotein (VLDL) receptor deficiencies, which account for elevated plasma VLDL and triglycerides in Imai rats at 34 weeks of age. In this study, we investigated key factors involved in cholesterol metabolism. Male Imai and Sprague-Dawley control rats were fed a regular rat chow and observed from age 8 through 34 weeks. Hepatic 3-hydroxy-3 methylglutaryl coenzyme A (HMG-CoA) reductase, cholesterol 7alpha-hydroxylase, low-density lipoprotein (LDL) receptor and acyl Co A:cholesterol acyltransferase (ACAT) were measured by Western blot and plasma lecithin:cholesterol acyltransferase (LCAT) protein was measured by enzyme-linked immunosorbent assay (ELISA). At 34 weeks of age, the Imai rats showed severe proteinuria, hypoalbuminemia, 60% reduction in glomerular filtration rate (GFR), elevated plasma total and LDL cholesterol and LDL/high-density lipoprotein (HDL) ratio. Imai rats showed a twofold elevation of hepatic HMG-CoA reductase, the rate-limiting step in cholesterol biosynthesis, but no significant change in cholesterol 7alpha-hydroxylase, the rate-limiting enzyme in cholesterol catabolism to bile acids. This was accompanied by and largely due to a threefold down-regulation of hepatic LDL receptor, which limits hepatic uptake of LDL; and a threefold up-regulation of hepatic ACAT (P < 0.01), which augments esterification of hepatocyte free cholesterol, thus, limiting cholesterol-mediated feedback regulation of cholesterol synthesis and catabolism. Moreover, plasma LCAT concentration was severely depressed (by fourfold) in Imai rats. This abnormality can impair HDL-mediated cholesterol transport from extrahepatic tissues to the liver. The study revealed marked abnormalities of the key proteins involved in regulation of hepatic cholesterol metabolism. These abnormalities can account for severe dysregulation of cholesterol metabolism in Imai rats with spontaneous FGS, which closely resembles FGS in humans.


[Challenges to Creation of Artificial Organelle for Effective Editing of Cell Function].
In "cell-function editing", the combination of biological methods with artificial methods is a promising way to effectively implement functions that live cells do not originally possess. In the present symposium review, two approaches with methodology of building "artificial organelle" were implemented for editing cellular functions. One approach is the "membrane-bound artificial organelle", which is mainly created from polymeric nanocapsules that function in cells, and the other approach mimics the "membraneless organelle", which has recently gained immense interest in the field of cell biology. Furthermore, some examples of artificial cells are also described, which were constructed by utilizing artificial organelles. In this context, some recent progress has been observed in the author's research on the development of polyion complex (PIC) materials, in particular, PICsome-based nanoreactors, designer coacervates for protein sequestration, and yolk-shell PIC structures that are reminiscent of artificial cells. These technologies may contribute to effective "cell editing" or "cell renovation", which enables the edited cells to show higher performance at the target site in the human body, compared to the native cells.


NMR analysis of DNA junctions: imino proton NMR studies of individual arms and intact junction.
The NMR resonances from the hydrogen-bonded guanine and thymine imino protons of base pairs in the four separate complexes forming the arms of a stable DNA four-arm junction have been assigned by using sequential nuclear Overhauser effects connecting protons in adjacent pairs. Comparison of the spectra of these individual duplex arms with that of the intact four-stranded junction suggests that base pairing occurs at the site of branching. The presence of new resonances in the spectrum of the junction can be inferred from comparison of the junction spectrum with the simulated spectra of the four individual arms. In addition, upfield shifts of the ring protons in the base pairs at the penultimate positions in the complex are observed, consistent with a change in the structure at the site of branching. These studies represent the first stage of a detailed analysis of the structure and dynamics of a DNA junction.


Five-coordinate MnIV intermediate in the activation of nature's water splitting cofactor.
Nature's water splitting cofactor passes through a series of catalytic intermediates (S0-S4) before O-O bond formation and O2 release. In the second last transition (S2 to S3) cofactor oxidation is coupled to water molecule binding to Mn1. It is this activated, water-enriched all MnIV form of the cofactor that goes on to form the O-O bond, after the next light-induced oxidation to S4 How cofactor activation proceeds remains an open question. Here, we report a so far not described intermediate (S3') in which cofactor oxidation has occurred without water insertion. This intermediate can be trapped in a significant fraction of centers (>50%) in (i) chemical-modified cofactors in which Ca2+ is exchanged with Sr2+; the Mn4O5Sr cofactor remains active, but the S2-S3 and S3-S0 transitions are slower than for the Mn4O5Ca cofactor; and (ii) upon addition of 3% vol/vol methanol; methanol is thought to act as a substrate water analog. The S3' electron paramagnetic resonance (EPR) signal is significantly broader than the untreated S3 signal (2.5 T vs. 1.5 T), indicating the cofactor still contains a 5-coordinate Mn ion, as seen in the preceding S2 state. Magnetic double resonance data extend these findings revealing the electronic connectivity of the S3' cofactor is similar to the high spin form of the preceding S2 state, which contains a cuboidal Mn3O4Ca unit tethered to an external, 5-coordinate Mn ion (Mn4). These results demonstrate that cofactor oxidation regulates water molecule insertion via binding to Mn4. The interaction of ammonia with the cofactor is also discussed.


FOSL1 modulates Schwann cell responses in the wound microenvironment and regulates peripheral nerve regeneration.
Peripheral glial Schwann cells switch to a repair state after nerve injury, proliferate to supply lost cell population, migrate to form regeneration tracks, and contribute to the generation of a permissive microenvironment for nerve regeneration. Exploring essential regulators of the repair responses of Schwann cells may benefit the clinical treatment for peripheral nerve injury. In the present study, we find that FOSL1, a AP-1 member that encodes transcription factor FOS Like 1, is highly expressed at the injured sites following peripheral nerve crush. Interfering FOSL1 decreases the proliferation rate and migration ability of Schwann cells, leading to impaired nerve regeneration. Mechanism investigations demonstrate that FOSL1 regulates Schwann cell proliferation and migration by directly binding to the promoter of EPH Receptor B2 (EPHB2) and promoting EPHB2 transcription. Collectively, our findings reveal the essential roles of FOSL1 in regulating the activation of Schwann cells and indicate that FOSL1 can be targeted as a novel therapeutic approach to orchestrate the regeneration and functional recovery of injured peripheral nerves.


Development of nitric oxide donors for the treatment of cardiovascular diseases.
Nitric oxide (NO) is a molecule that dynamically modulates the physiological functions of the cardiovascular system, which include relaxation of vascular smooth muscle, inhibition of platelet aggregation, and regulation of immune responses. Because a reduced NO level has been implicated in the onset and progression of various disease states, NO is expected to provide therapeutic benefits in the treatment of cardiovascular diseases, such as essential hypertension, stroke, coronary artery disease, atherosclerosis, platelet aggregation after percutaneous transluminal coronary angioplasty, and ischemia/reperfusion injury. To date, pharmacologically active compounds that can release NO within the body, such as organic nitrates and sodium nitroprusside, have been used as therapeutic agents, but their efficacy is significantly limited by their rapid NO release, poor distribution to the target site, toxicity, and induction of tolerance. Therefore, new NO donors with better pharmacological and pharmacokinetic properties would be highly desirable. In this review, recent challenges in the development of new NO donors and NO delivery systems are summarized. Then, future developments of novel NO donors are also discussed in order to optimize NO delivery in the treatment of cardiovascular diseases.


Effects of leptin on endothelial function with OB-Rb gene transfer in Zucker fatty rats.
The metabolic syndrome in association with obesity is a major clinical problem inducing hypertension, diabetes mellitus, and atherosclerosis. Leptin induces angiogenesis by its proliferative effects on endothelial cells (ECs) via OB receptor (OB-Rb) gene. We evaluated the growth of ECs and intracellular signalings in response to leptin in vitro and the angiogenic effects of leptin in the cornea in vivo with and without adenovirus-mediated transfer of the OB-Rb gene in Zucker fatty (ZF) rats as a model for the metabolic syndrome. Recombinant adenovirus vector encoding rat OB-Rb (Ad.OB-Rb) or Escherichia coli. LacZ (Ad.LacZ) was transfected into cultured ECs from Zucker lean (ZL) rats and ZF rats. Leptin increased DNA synthesis dose-dependently in ECs from ZL rats but not ZF rats. Infection with Ad.OB-Rb, but not with Ad.LacZ, improved the growth effects of leptin in ECs from ZF rats. Leptin induced phosphorylation of Janus kinase (JAK)2, signal transducer and activator of transcription (STAT)3, and extracellular signal-regulated kinase (ERK) in ECs from ZL rats but not ZF rats. Infection with Ad.OB-Rb restored phosphorylation of JAK2 and STAT3 in ECs from ZF rats. Leptin induced angiogenesis in cornea from ZL rats, but not from ZF rats. Coadministration of leptin and Ad.OB-Rb induced angiogenesis in cornea from ZF rats. Ad.LacZ did not influence the angiogenic effects of leptin. The impaired endothelial function with the leptin resistance may be one of causes of the atherosclerosis in the metabolic syndrome.


[Results of studies of human dirofilariasis in Russia].
Human dirofilariasis is a pressing health problem in Russia. By 2014, there have been as many as 850 Dirofilaria repens-infested people living in 42 subjects of the Russian Federation. One of the favorable factors for circulation and spread of invasion is a temperature of above +20-24 degrees C; when the latter is maintained during at least 20 days there may be 1.-1.5 circulations of invasion in the carrier and a 2.8-fold increase in transmission intensity. The border ofa dirofilariasis area with a temperate climate is southward to 58 degrees N in European Russia and West Siberia and southward to 50 degrees N in the Far East. The conditions in the human body have been found to be more favorable for the development of Dirofilaria than considered before and allow the helminth to achieve sexual maturity and to propagate. If man has microfilaremia, he may be a source of invasion. It is necessary to examine venous blood by the enrichment method and, if possible, polymerase chain reaction and enzyme immunoassay, which make it possible to establish a diagnosis in occult invasion and to identify a pathogen species.


Modification of non-stomatal limitation and photoprotection due to K and Na nutrition of olive trees.
Potassium (K) is an essential macronutrient shown to play a fundamental role in photosynthetic processes and may facilitate photoinhibition resistance. In some plant species, sodium (Na) can partially substitute for K. Although photosynthetic enhancement has been well established, the mechanisms by which K or Na affects photosynthesis are not fully understood. Olive (Olea europaea L.) trees were previously shown to benefit from Na nutrition when K is limiting. In order to study the effect of K and Na on photosynthetic performance, we measured gas exchange and chlorophyll fluorescence in young olive trees supplied with either K, Na or no fertilizer, and subjected to manipulated levels of CO2, O2 and radiation. Light and CO2 response curves indicate substantially superior photosynthetic capacity of K-sufficient trees, while Na substitution generated intermediate results. The enhanced performance of K, and to a lesser extent, Na-supplied trees was found to be related mainly to modification of non-stomatal limitation. This indicates that K deficiency promotes inhibition of enzymatic-photochemical processes. Results indicate lower chlorophyll content and altered Rubisco activity as probable causes of photosynthetic impairment. Potassium deficiency was found to diminish photoprotection mechanisms due to reduced photosynthetic and photorespiratory capacity. The lower CO2 and O2 assimilation rate in K-deficient trees caused elevated levels of exited energy. Consequently, non-photochemical quenching, an alternative energy dispersion pathway, was increased. Nonetheless, K-deficient trees were shown to suffer from photodamage to photosystem-II. Sodium replacement considerably diminished the negative effect of K deficiency on photoprotection mechanisms. The overall impact of K and Na nutrition plays down any indirect effect on stomatal limitation and rather demonstrates the centrality of these elements in photochemical processes of photosynthesis and photoprotection.


Isolation, structure elucidation, and biological activity of altersolanol P using Staphylococcus aureus fitness test based genome-wide screening.
Bacteria continue to evade existing antibiotics by acquiring resistance by various mechanisms, leading to loss of antibiotic effectiveness. To avoid an epidemic from infections of incurable drug-resistant bacteria, new antibiotics with new modes of action are desperately needed. Using a genome-wide mechanism of action-guided whole cell screening approach based on antisense Staphylococcus aureus fitness test technology, we report herein the discovery of altersolanol P (1), a new tetrahydroanthraquinone from an unknown fungus from the Hypocreales isolated from forest litter collected in Puerto Rico. The structure was elucidated by high-resolution mass spectrometry and 2D NMR spectroscopy. Relative stereochemistry was established by NOESY correlations, and absolute configuration was deduced by the application of MPA ester-based methodology. Observed (1)H and (13)C NMR shifts were well aligned with the corresponding chemical shifts predicted by DFT calculations. Altersolanol P exhibited Gram-positive antibacterial activity (MIC range 1-8 μg/mL) and inhibited the growth of Gram-negative Haemophilus influenzae (MIC 2 μg/mL). The isolation, structure elucidation, and antibacterial activity of altersolanol P are described.


Implementation of a COPD Screening Questionnaire in an Outpatient HIV Clinic.
Human immunodeficiency virus (HIV) is associated with increased risk for chronic obstructive pulmonary disease (COPD); yet substantial under-recognition of COPD exists. We administered a patient-completed, physician-reviewed COPD screening tool in an outpatient HIV clinic to determine whether screening is feasible or possible. Patients attending nonacute, routine HIV care visits were provided a brief COPD screening tool, which included three questions focused on age, respiratory symptoms, and smoking history. Providers were given completed forms for review and ordered spirometry at their discretion. Forms and medical records were subsequently reviewed to determine completion and results of spirometry testing. Of the 1,510 patients screened during the study period, 968 (64%) forms were completed. After excluding 79 incomplete forms, 889 (92%) unique patient forms were included in this analysis. Among these, 204 (23%) met criteria for spirometry referral, among whom physicians ordered spirometry in 64 (31%). At 6 months following study completion, 19 (30%) of the patients referred for spirometry had the test completed, with 5 (26%) demonstrating airflow obstruction. Nearly one out of four HIV patients met indication for screening spirometry and roughly one out of four undergoing spirometry had COPD. Critical drop-offs in the screening and diagnostic process occurred at questionnaire completion and spirometry ordering. Interventions tailored to these critical steps could improve the yield from COPD screening and help to optimize the identification of COPD in high-risk HIV-infected populations. COPD screening in a clinic focused on longitudinal HIV care can effectively identify COPD among those completing the screening continuum.


The rising incidence of second cancers: patterns of occurrence and identification of risk factors for children and adults.
As the population of cancer survivors has increased and continues to age, the occurrence of second cancers has risen dramatically-from 9% of all cancer diagnoses in 1975-1979 to 19% in 2005-2009. The Childhood Cancer Survivor Study, a cohort of more than 14,000 childhood cancer survivors with detailed exposure data and long-term follow-up, has substantially contributed to our understanding of the roles of radiotherapy and chemotherapy in second cancer occurrence. In particular, dose-related risks have been demonstrated for second cancers of the breast, thyroid, central nervous system, gastrointestinal tract, and sarcomas following radiation. Cytotoxic chemotherapy-which has long been known to be leukemogenic-also appears to contribute to risk for a range of other second cancer types. Individuals who develop a second cancer are at particularly high risk for developing additional second cancers. A genome-wide association study of survivors of Hodgkin lymphoma who received radiotherapy identified a locus on chromosome 6q21 as being associated with second cancer risk, demonstrating that recent advances in genomics are likely to prove invaluable for elucidating the contribution of genetic susceptibility to second cancer etiology. Among adults, risk of second cancers varies substantially by type of first and second cancer, patient age, and prevalence of second cancer risk factors, including primary cancer treatments, environmental and lifestyle exposures, and genetic susceptibility. Further research is needed to quantify second cancer risks associated with specific etiologic factors and to identify the patients at highest risk of developing a second cancer to target prevention and screening efforts.


Synthesis of (2-hydroxyphenyl)(fusedphenyl)methanones via the photo-induced rearrangement of 2'-arylisoflavones.
The photo-induced rearrangement of 2'-arylisoflavones (aryl = phenyl, furyl, 3-pyridyl, 1-naphenyl, and 2-naphenyl) for the synthesis of (2-hydroxyphenyl)(fused phenyl)methanones in EtOH under an Ar atmosphere at room temperature has been developed. The described method proceeded smoothly without requiring any transition metal catalyst, oxidant, or additives. Moreover, using ethanol as the solvent is not only cost efficient but also environmentally friendly. Further treatment of methanone analogues with AlCl3 yielded highly conjugated polycyclic aromatic hydrocarbon (PAH) derivatives.


Structure of d(TGCGCA)2 and a comparison to other DNA hexamers.
The X-ray crystal structure of d(TGCGCA)2 has been determined at 120 K to a resolution of 1.3 A. Hexamer duplexes, in the Z-DNA conformation, pack in an arrangement similar to the 'pure spermine form' [Egli et al. (1991). Biochemistry, 30, 11388-11402] but with significantly different cell dimensions. The phosphate backbone exists in two equally populated discrete conformations at one nucleotide step, around phosphate 11. The structure contains two ordered cobalt hexammine molecules which have roles in stabilization of both the Z-DNA conformation of the duplex and in crystal packing. A comparison of d(TGCGCA)2 with other Z-DNA hexamer structures available in the Nucleic Acid Database illustrates the elusive nature of crystal packing. A review of the interactions with the metal cations Na+, Mg2+ and Co3+ reveals a relatively small proportion of phosphate binding and that close contacts between metal ions are common. A prediction of the water structure is compared with the observed pattern in the reported structure.


Role of renal kallikrein in the regulation of blood pressure in the rat remnant kidney model of chronic renal failure.
We studied urinary excretion of active and inactive kallikrein every day for 3 weeks in spontaneously hypertensive rats (SHR) and Wistar-Kyoto rats (WKY) subjected to 5/6 nephrectomy (5/6), 1/2-nephrectomy (1/2) or sham-operation (Sham). We determined urinary active and inactive kallikrein by measuring kallikrein activity using a kininogenase assay before and after treatment with trypsin (200 micrograms/ml). In the SHR group, blood pressure was significantly elevated in 5/6-animals as compared with 1/2 or sham, whereas in the WKY group blood pressure was not changed after either operation. Urinary active and total kallikrein excretion were decreased in 5/6-SHR to 34% and 59%, respectively, as compared with values of sham-SHR, and in 1/2-SHR to 70% and 70%, respectively. Similarly, they were also decreased in 5/6-WKY to 36% and 55%, respectively, as compared with values of sham-WKY. In 1/2-WKY urinary active kallikrein excretion was decreased to 88% as compared with the value of sham-WKY, but urinary total kallikrein excretion was not different from that of sham-WKY. Thus, the suppressed renal kallikrein activity due to reduced renal mass was not associated with any significant change in blood pressure in WKY, although it induced an elevation of blood pressure in SHR. These results indicate that the decreased production of renal active kallikrein may not play a significant role in the regulation of blood pressure in the rat remnant kidney model of chronic renal failure. In addition, it is suggested that the elevation of blood pressure in this model of SHR may be due to other factors than renal kallikrein.


[The comparative characterization of different forms of myocardial infarction at a 30-year interval].
The paper presents the results of morphological and morphometrical studies of 247 subjects who have died from diferent forms of myocardial infarction (MI) in comparison with those of the study conducted by G. G. Avtandilov and K. D. Salbiyev 30 years ago. The performed study demonstrates that general trends in the occurrence and development of MI have undergone no substantial changes in the past 30years. The reduction in the count of platelets from 50 to 30% may be due to the advent of more effective anriaggregants and the use of current thrombolytics during both emergency care delivery and acute MI treatment. It is rather difficult to macroscopically define the borders of infarction at 72 hours after its onset for the pathological processes progress and the extent of infarction is expanded.


Inoperable esophageal cancer and outcome of palliative care.
To determine the outcome of esophageal cancer patients referred for palliative care, in Gorgan and Gonbad gastrointestinal clinics, northeast of Iran. This cross-sectional study was done on inoperable esophageal cancer cases referred to gastrointestinal clinics in Gorgan and Gonbad city (2005-2006). Demographic data were collected during the procedure and cases were followed up every one month. Improvement proportion was calculated with 95% confidence interval, to determine the rate of improvement. Survival analysis and Kaplan-Meier methods were used to estimate the duration of palliative care effectiveness. We recruited 39 cases into the study. Squamous cell carcinoma was the most prevalent (92.3%). The middle third of the esophagus was involved predominantly (51.3%). Dilation was the most preferred method (89.7%) and stenting was done in 4 cases. Decreasing dysphagia score was not related to palliation method or pathology type of carcinoma. Age of the patients was significantly related to the improvement of dysphagia score. Mean survival time was 137.6 d and median was 103 d. Results of this study showed a low survival rate after palliative care in esophageal cancer cases despite dysphagia scores' improvement after dilating or stenting.


Cell signaling microdomain with Na,K-ATPase and inositol 1,4,5-trisphosphate receptor generates calcium oscillations.
Recent studies indicate novel roles for the ubiquitous ion pump, Na,K-ATPase, in addition to its function as a key regulator of intracellular sodium and potassium concentration. We have previously demonstrated that ouabain, the endogenous ligand of Na,K-ATPase, can trigger intracellular Ca2+ oscillations, a versatile intracellular signal controlling a diverse range of cellular processes. Here we report that Na,K-ATPase and inositol 1,4,5-trisphosphate (InsP3) receptor (InsP3R) form a cell signaling microdomain that, in the presence of ouabain, generates slow Ca2+ oscillations in renal cells. Using fluorescent resonance energy transfer (FRET) measurements, we detected a close spatial proximity between Na,K-ATPase and InsP3R. Ouabain significantly enhanced FRET between Na,K-ATPase and InsP3R. The FRET effect and ouabain-induced Ca2+ oscillations were not observed following disruption of the actin cytoskeleton. Partial truncation of the NH2 terminus of Na,K-ATPase catalytic alpha1-subunit abolished Ca2+ oscillations and downstream activation of NF-kappaB. Ouabain-induced Ca2+ oscillations occurred in cells expressing an InsP3 sponge and were hence independent of InsP3 generation. Thus, we present a novel principle for a cell signaling microdomain where an ion pump serves as a receptor.


Metabolic function of a suboptimal transplanted islet mass in nonhuman primates on rapamycin monotherapy.
Although islet transplantation may restore insulin independence to individuals with type 1 diabetes mellitus, most have abnormal glucose tolerance. We asked whether the defective glucose tolerance is due to inadequate β-cell mass or to impaired insulin sensitivity. We performed metabolic studies on four cynomolgus primates before inducing diabetes with streptozotocin (STZ), then again 2-3 weeks after restoring insulin independence via intrahepatic islet transplantation utilizing a calcineurin inhibitor-free immunosuppressive regimen (induction with rabbit antithymocyte globulin and maintenance therapy with rapamycin). Engrafted β-cell mass was assessed by acute insulin and C-peptide responses to glucose (AIR(glu) and ACR(glu)) and arginine (AIR(arg) and ACR(arg)). Insulin sensitivity (S(I)) was determined in naive and transplanted primates from an intravenous glucose tolerance test using the minimal model. α-Cell function was determined by the acute glucagon response to arginine (AGR(arg)). Glucose tolerance (K(g)) decreased from 4.1 ± 0.5%/min in naive primates to 1.8 ± 0.3%/min in transplanted primates (p < 0.01). Following transplantation, AIR(glu) was 28.7 ± 13.1 μU/ml compared to 169.9 ± 43.1 μU/ml (p < 0.03) in the naive condition, ACR(glu) was 14.5 ± 6.0 ng/ml compared to 96.5 ± 17.0 ng/ml naive (p < 0.01), AIR(arg) was 29.1 ± 13.1 μU/ml compared to 91.4 ± 28.2 μU/ml naive (p < 0.05), and ACR(arg) was 1.11 ± 0.51 ng/ml compared to 2.79 ± 0.77 ng/ml naive (p < 0.05). S(I) did not differ from naive to posttransplant states. AGR(arg) was reduced in transplanted primates (349 ± 118 pg/ml) when compared to both naive (827 ± 354 pg/ml) and post-STZ diabetic primates (1020 ± 440 pg/ml) (p < 0.01 for both comparisons). These data suggest that impaired glucose tolerance observed in islet transplant recipients is secondary to low functional β-cell mass and not to insulin resistance shortly after transplant. Furthermore, improved glycemic control achieved via islet transplantation over the diabetic state might be attained, in part, via reduced glucagon secretion.


Proof of efficacy of Kamillosan(R) cream in atopic eczema.
Kamillosan(R) cream contains chamomile extract as active principle manufactured from the chamomile sort Manzana which is rich in active principles and has been proved not to exhibit a chamomile-related allergen potential. For this reason Kamillosan(R) cream is suited for local therapy of atopic eczema. In a partially double-blind, randomized study carried out as a half-side comparison, Kamillosan(R) cream was tested vs. 0.5% hydrocortisone cream and the vehicle cream as placebo in patients suffering from medium-degree atopic eczema. After a 2-week treatment Kamillosan(R) cream showed a mild superiority towards 0.5% hydrocortisone and a marginal difference as compared to placebo.


Autoantibody against peroxiredoxin I, an antioxidant enzyme, in patients with systemic sclerosis: possible association with oxidative stress.
To determine the prevalence and clinical correlation of autoantibody to peroxiredoxin (Prx) I, an antioxidant enzyme, in patients with systemic sclerosis (SSc). Serum samples from SSc patients (n = 70) and healthy controls (n = 23) were examined by ELISA using human recombinant Prx I. The presence of anti-Prx I antibody was further evaluated by immunoblotting analysis. To determine the functional relevance of anti-Prx I antibody in vivo, we assessed whether anti-Prx I antibody was able to inhibit Prx I enzymatic activity using yeast thioredoxin reductase system. IgG anti-Prx I antibody levels in SSc patients were significantly higher than healthy controls and this autoantibody was detected in 33% of SSc patients. The presence of IgG anti-Prx I antibody was associated with longer disease duration, more frequent presence of pulmonary fibrosis, heart involvement, and anti-topoisomerase I antibody and increased levels of serum immunoglobulin and erythrocyte sedimentation rates. IgG anti-Prx I antibody levels also correlated positively with renal vascular damage and negatively with pulmonary function tests. Furthermore, anti-Prx I antibody levels correlated positively with serum levels of 8-isoprostane, a marker of oxidative stress. Immunoblotting analysis confirmed the presence of anti-Prx I antibody. Remarkably, Prx I enzymatic activity was inhibited by IgG isolated from SSc sera containing IgG anti-Prx I antibody. These results suggest that elevated IgG anti-Prx I autoantibody is associated with the disease severity of SSc and that anti-PrxI antibody may enhance the oxidative stress by inhibiting Prx I enzymatic activity.


Bi-layered polyurethane - Extracellular matrix cardiac patch improves ischemic ventricular wall remodeling in a rat model.
As an intervention to abrogate ischemic cardiomyopathy, the concept of applying a temporary, local patch to the surface of the recently infarcted ventricle has been explored from a number of design perspectives. Two important features considered for such a cardiac patch include the provision of appropriate mechanical support and the capacity to influence the remodeling pathway by providing cellular or biomolecule delivery. The objective of this report was to focus on these two features by first evaluating the incorporation of a cardiac extracellular matrix (ECM) component, and second by evaluating the impact of patch anisotropy on the pathological remodeling process initiated by myocardial infarction. The functional outcomes of microfibrous, elastomeric, biodegradable cardiac patches have been evaluated in a rat chronic infarction model. Ten weeks after infarction and 8 wk after patch epicardial placement, echocardiographic function, tissue-level structural remodeling (e.g., biaxial mechanical response and microstructural analysis), and cellular level remodeling were assessed. The results showed that the incorporation of a cardiac ECM altered the progression of several keys aspects of maladaptive remodeling following myocardial infarction. This included decreasing LV global mechanical compliance, inhibiting echocardiographically-measured functional deterioration, mitigating scar formation and LV wall thinning, and promoting angiogenesis. In evaluating the impact of patch anisotropy, no effects from the altered patch mechanics were detected after 8 wk, possibly due to patch fibrous encapsulation. Overall, this study demonstrates the benefit of a cardiac patch design that combines both ventricle mechanical support, through a biodegradable, fibrillary elastomeric component, and the incorporation of ECM-based hydrogel components.


Is genetic counseling a stressful event?
The aim of this paper was to investigate whether cancer genetic counseling could be considered as a stressful event and associated with more anxiety and/or depression compared to other cancer-related events for instance attending mammography screening or receiving a cancer diagnosis. A total of 4911 individuals from three Scandinavian countries were included in the study. Data was collected from individuals who had attended either cancer genetic counseling (self-referred and physician-referred) or routine mammography screening, were recalled for a second mammograpy due to a suspicious mammogram, had received a cancer diagnosis or had received medical follow-up after a breast cancer-surgery. Data from the genetic counseling group was also compared to normative data. Participants filled in the Hospital Anxiety and Depression Scale twice: prior to a potentially stressful event and 14 days after the event. Pre-counseling cancer genetic counselees reported significant lower level of anxiety compared to the cancer-related group, but higher levels of anxiety compared to the general population. Furthermore, the level of depression observed within the genetic counseling group was lower compared to other participants. Post-event there was no significant difference in anxiety levels between the cancer genetic counselees and all other groups; however, the level of depression reported in the self-referred group was significantly lower than observed in all other groups. Notably, the level of anxiety and depression had decreased significantly from pre-to post-events within the genetic counseling group. In the cancer-related group only the level of anxiety had decreased significantly post-event. Individuals who attend cancer genetic counseling do not suffer more anxiety or depression compared to all other cancer-related groups. However, some counselees might need additional sessions and extended support. Thus, identifying extremely worried individuals who need more support, and allocating further resources to their care, seems to be more sufficient.


Omanicotyle heterospina n. gen. et n. comb. (Monogenea: Microcotylidae) from the gills of Argyrops spinifer (Forsskål) (Teleostei: Sparidae) from the Sea of Oman.
The Sultanate of Oman's aquaculture industry is expanding with an on-going assessment of potential new fish species for culture. The king soldier bream, Argyrops spinifer (Forsskål) (Sparidae), is one such species that is under consideration. During a routine health assessment of specimens caught in the Sea of Oman throughout the period November 2009 to March 2011, a number of gill polyopisthocotylean monogeneans were recovered. A subsequent study of the monogeneans using a range of morphology-based approaches indicated that these were Bivagina heterospina Mamaev et Parukhin, 1974. In the absence of pre-existing molecular data, an expanded description of this species is provided, including a differential diagnosis with other species and genera belonging to the subfamily Microcotylinae Monticelli, 1892 with the subsequent movement of this species to a new genus to accommodate it. The polyopisthocotyleans collected from the gills of A. spinifer appear to be unique within the family Microcotylidae Taschenberg, 1879 in that, morphologically, they possess a pair of large, muscular vaginae each armed with a full crown of 16-18 robust spines and a unique dorsal region of folded tegument, which permits their discrimination from species of Bivagina Yamaguti, 1963. Sequencing of the SSU rDNA (complete 1968 bp) and LSU rDNA (partial 949 bp) places the specimens collected during this study within the subfamily Microcotylinae, but the LSU rDNA sequence differs from Bivagina and also from other microcotylid genera. Morphological features of B. heterospina sensu Mamaev et Parukhin, 1974 and the specimens collected from the current study are consistent with one another and represent a single species. The vaginal armature of these worms is unique and differs from all other genera within the Microcotylinae, including Bivagina, and its movement to Omanicotyle n. gen. to accommodate this species is proposed. A new genus, Omanicotyle n. gen., is erected to accommodate Omanicotyle [Bivagina] heterospina n. comb. which represents the first monogenean to be described from Omani marine waters. Given the pathogenic potential of microcotylids on captive held fish stocks, a full assessment of Omanicotyle heterospina n. gen. et n. comb. is now required before large-scale production commences.


Modification and Validation of an mHealth App Quality Assessment Methodology for International Use: Cross-sectional and eDelphi Studies.
Over 325,000 mobile health (mHealth) apps are available to download across various app stores. However, quality assurance in this field of medicine remains relatively undefined. Globally, around 84% of the population have access to mobile broadband networks. Given the potential for mHealth app use in health promotion and disease prevention, their role in patient care worldwide is ever apparent. Quality assurance regulations both nationally and internationally will take time to develop. Frameworks such as the Mobile App Rating Scale and Enlight Suite have demonstrated potential for use in the interim. However, these frameworks require adaptation to be suitable for international use. This study aims to modify the Enlight Suite, a comprehensive app quality assessment methodology, to improve its applicability internationally and to assess the preliminary validity and reliability of this modified tool in practice. A two-round Delphi study involving 7 international mHealth experts with varied backgrounds in health, technology, and clinical psychology was conducted to modify the Enlight Suite for international use and to improve its content validity. The Modified Enlight Suite (MES) was then used by 800 health care professionals and health care students in Ireland to assess a COVID-19 tracker app in an online survey. The reliability of the MES was assessed using Cronbach alpha, while the construct validity was evaluated using confirmatory factor analysis. The final version of the MES has 7 sections with 32 evaluating items. Of these items, 5 were novel and based on consensus for inclusion by Delphi panel members. The MES has satisfactory reliability with a Cronbach alpha score of .925. The subscales also demonstrated acceptable internal consistency. Similarly, the confirmatory factor analysis demonstrated a positive and significant factor loading for all 32 items in the MES with a modestly acceptable model fit, thus indicating the construct validity of the MES. The Enlight Suite was modified to improve its international relevance to app quality assessment by introducing new items relating to cultural appropriateness, accessibility, and readability of mHealth app content. This study indicates both the reliability and validity of the MES for assessing the quality of mHealth apps in a high-income country, with further studies being planned to extrapolate these findings to low- and middle-income countries.


Anesthetic myocardial protection with sevoflurane.
To examine the role of sevoflurane in myocardial protection in patients undergoing coronary artery bypass graft (CABG) surgery. Prospective, randomized, controlled, double-blinded study. Veterans Administration Medical Center (VAMC), Buffalo, New York. Twenty-one patients undergoing CABG were included in the study. Eleven patients were randomized to receive sevoflurane, and 10 patients served as controls. Total intravenous anesthesia was provided for both study and control groups by infusion of propofol, fentanyl, and midazolam. Sevoflurane 2% was added to the cardioplegia solution in the experimental group. Neutrophil beta-integrins (CD11b/CD18), tumor necrosis factor alpha (TNF-alpha), and interleukin (IL)-6 were measured as indicators of the inflammatory response to myocardial ischemia-reperfusion injury. Blood samples were obtained from the aorta and coronary sinus before (T1) and immediately after cardiopulmonary bypass (CPB) (T2) and, in addition, from a peripheral artery 6 hours (T3) after CPB. Myocardial function was determined in all patients at each time point. Left ventricular stroke work index (LVSWI) was calculated as an estimation of left ventricular function. Left ventricular regional wall motion abnormality (RWMA) was assessed by transesophageal echocardiography at T1 and T2 time points. TNF-alpha was detectable only in the control group in arterial samples at T3. IL-6 levels (pg/mL) were found to be lower in the sevoflurane group compared with controls at T2 arterial circulation (38.2 +/- 21.1 v 60.6 +/- 19.1, p < 0.05) as well as in the coronary circulation (38.4 +/- 19.9 v 118.2 +/- 23.5, p < 0.01) at T2. CD11b/CD18 increased 79% after CPB in the control group while only increasing 36% in the sevoflurane group (p < 0.05). The post-CPB LVSWI was back to its baseline values in the sevoflurane group, whereas it was still significantly depressed in the control group. Eight of 10 patients in the control group showed a transient new-onset RWMA in either the septal or anteroseptal regions. Only 2 of 11 patients in the sevoflurane group showed transient RWMA of the LV. Sevoflurane decreases the inflammatory response after CPB, as measured by the release of IL-6, CD11b/CD18, and TNF-alpha. Myocardial function after CPB, as assessed by RWMA and LVSWI, was also improved with sevoflurane. The role of sevoflurane in myocardial protection and the inflammatory response to myocardial reperfusion should be considered.


Allogeneic transplant of canine peripheral blood stem cells mobilized by recombinant canine hematopoietic growth factors.
We have studied graft-versus-host disease (GVHD) after transplantation of allogeneic peripheral blood stem cells (PBSC) mobilized by either recombinant canine granulocyte colony-stimulating factor (rcG-CSF) alone or combined with stem cell factor (rcSCF). These studies were prompted by the observation of extremely rapid and sustained engraftment of growth factor-mobilized PBSC in the autologous setting using genetically marked cells and changes in function of T lymphocytes from donors that had undergone mobilization. Specifically, lymphocytes from growth factor-treated donors were hyporesponsive in mixed leukocyte culture and in response to Con A, raising hopes that GVHD in dogs given growth factor mobilized allogenic PBSC might be altered in a beneficial way. Eighteen dogs were given a median of 17.1 x 10(8) PBSC/kg from littermate donors after 920 cGy of total body irradiation without postgrafting immunosuppression. Donors were either genotypically DLA-identical (n = 9) or DLA-haploidentical (n = 9). The median number of colony-forming unit-granulocyte macrophage (CFU-GM) infused was 27 x 10(4)/kg, and the number of CD34+ cells in the transplant was on the order of 4.6 x 10(6)/kg. The dogs received a median of 52.8 x 10(7) CD4 cells/kg and 13.7 X 10(7) CD8 cells/kg. All 18 dogs had prompt hematopoietic engraftment of donor cells as assessed by chimerism studies using variable number tandem repeat, as well as cytogenetic markers. Three of the nine dogs given grafts from DLA-identical littermates had fatal GVHD, five had transient GVHD, and one had no GVHD. All nine DLA-haploidentical recipients of PBSC developed fatal hyperacute GVHD. In conclusion, the expectation about rapid engraftment was fulfilled. However, incidence and severity of acute GVHD after transplantation of mobilized PBSC were not different than previously reported for nonmobilized PBSC or marrow. This model will allow for further studies, including T-cell depletion to minimize GVHD without increasing graft rejection.


The biphasic effect of triiodothyronine compared to bone resorbing effect of PTH on bone modelling of mouse long bone in vitro.
To examine the effects of T3 on fetal long bone modelling the radii and ulnae of 16 day old fetal mice were grown in vitro for two days. Their growth, mineralization, and resorption were assessed by measuring diaphyseal length, calcium and phosphorus content, hydroxyproline content, and the release of incorporated 45Ca. The effects of T3 were compared to the effects of 1-34 PTH, a known resorbing agent, on the same system. Devitalized bones were used as a control. The results showed that T3 had a biphasic effect. At high concentrations (10(-5) M-10(-6) M) T3 inhibited the growth of the bones as indicated by their diaphyseal length and hydroxyproline content. Calcium and phosphorus content were significantly decreased while 45Ca release was increased. Similar effects were also found after the addition of 1-34 PTH to the media. However, T3, at lower concentrations (10(-7) M-10(-9) M), stimulated the growth and calcification of the bones as indicated by an increase in diaphyseal length and the hydroxyproline, calcium, and phosphorus content. 45Ca release was significantly decreased at these concentrations. Neither T3 nor 1-34 PTH affected devitalized bones in the same system. The results suggest that at physiological concentrations, T3 has a direct, anabolic effect on bone, which may explain its major role in the growth process of various species. At high doses, however, T3 stimulates bone resorption in a way similar to PTH.


A strategy to assess spillover risk of bat SARS-related coronaviruses in Southeast Asia.
Emerging diseases caused by coronaviruses of likely bat origin (e.g. SARS, MERS, SADS and COVID-19) have disrupted global health and economies for two decades. Evidence suggests that some bat SARS-related coronaviruses (SARSr-CoVs) could infect people directly, and that their spillover is more frequent than previously recognized. Each zoonotic spillover of a novel virus represents an opportunity for evolutionary adaptation and further spread; therefore, quantifying the extent of this "hidden" spillover may help target prevention programs. We derive biologically realistic range distributions for known bat SARSr-CoV hosts and quantify their overlap with human populations. We then use probabilistic risk assessment and data on human-bat contact, human SARSr-CoV seroprevalence, and antibody duration to estimate that ∼400,000 people (median: ∼50,000) are infected with SARSr-CoVs annually in South and Southeast Asia. These data on the geography and scale of spillover can be used to target surveillance and prevention programs for potential future bat-CoV emergence.


Beri-beri: the major cause of infant mortality in Karen refugees.
During a prospective evaluation of malaria prophylaxis in pregnancy in a refugee population on the north-western border of Thailand from 1987 to 1990, an extremely high infant mortality rate (18%) was documented despite good access to health care. Infantile beri-beri was recognized as the main cause of death accounting for 40% of all infant mortality. Thereafter, severe vitamin B1 deficiency in infants was diagnosed and treated promptly. The impact of this was assessed prospectively from 1993 to 1996 in a second cohort study. The case fatality of infantile beri-beri fell from almost 100% to 7%. The overall infant mortality rates declined from 183 to 78 per 1000 live births. Post-neonatal deaths fell by 79% (95% CI 65-87%) while neonatal mortality remained unchanged. Mortality resulting from acute respiratory infections did not change (15 and 11 per 1000, respectively), whereas mortality attributable to beri-beri decreased from 73 to 5 per 1000 (P < 0.0001). Before its recognition approximately 7% of all infants in this population died from infantile beri-beri. This lethal but preventable syndrome may be more common than hitherto recognized, particularly in refugee populations, in this populous region.


Vitamin D pathway gene variants and prostate cancer prognosis.
Observational studies linking vitamin D deficiency with increased prostate cancer (PCa) mortality and the pleiotropic anticancer effects of vitamin D in malignant prostate cell lines have initiated trials examining potential therapeutic benefits of vitamin D metabolites. There have been some successes but efforts have been hindered by risk of inducing hypercalcemia. A limited number of studies have investigated associations between variants in vitamin D pathway genes with aggressive forms of PCa. Increased understanding of relevant germline genetic variation with disease outcome could aid in the development of vitamin-D-based therapies. We undertook a comprehensive analysis of 48 tagging single-nucleotide polymorphisms (tagSNPs) in genes encoding for vitamin D receptor (VDR), vitamin D activating enzyme 1-alpha-hydroxylase (CYP27B1), and deactivating enzyme 24-hydroxylase (CYP24A1) in a cohort of 1,294 Caucasian cases with an average of 8 years of follow-up. Disease recurrence/progression and PCa-specific mortality risks were estimated using adjusted Cox proportional hazards regression. There were 139 cases with recurrence/progression events and 57 cases who died of PCa. Significantly altered risks of recurrence/progression were observed in relation to genotype for two VDR tagSNPs (rs6823 and rs2071358) and two CYP24A1 tagSNPs (rs927650 and rs2762939). Three VDR tagSNPs (rs3782905, rs7299460, and rs11168314), one CYP27B1 tagSNP (rs3782130), and five CYP24A1 tagSNPs (rs3787557, rs4809960, rs2296241, rs2585428, and rs6022999) significantly altered risks of PCa death. Genetic variations in vitamin D pathway genes were found to alter both risk of recurrence/progression and PCa-specific mortality.


Hypersensitivity reactions in small intestine. I Thymus dependence of experimental 'partial villous atrophy'.
Rats infected with the intestinal nematode Nippostrongylus brasiliensis have crypt hyperplasia with villous atrophy in affected areas of the small intestine. In thymus-deprived (B) rats the course of infection is prolonged but, despite the presence of many worms in the intestinal lumen, villi and crypts appear largely normal. This suggests that the tissue damaged associated with N. brasilliensis infection is caused, not by the worms, but by a local thymus-dependent immune reaction. There is some evidence to implicate lymphocytes rather than antibodies in this reaction. It is already know that T-cell-associated damage to the small intestine, such as occurs in allograft rejection, produces subtotal villous atrophy. The present findings suggest that when T cell react locally with helminth antigens a similar type of damage occurs. The presence of a local cell-mediated immune reaction may be the common factor which causes villous atrophy and crypt hyperplasia in many small intestinal diseases, eg, viral enteritis, giardiasis, cow's milk allergy, and coeliac disease.


[Helminths of birds and mammals from Israel. VI. The taxonomy and ecology of Trichostrongylid Nematodes (author's transl)].
Thirteen species of trichostronglyloid nematodes have so far been recorded from wild birds and mammals in Israel and surrounding territories. Three species were found in birds: Amidostomum fulicae (Rudolphi, 1819) in Fulica atra L., 1758, A. acutum (Lundahl, 1848) in Anas crecca L., 1758 AND Amidostomum sp. in Ceryle rudis L., 1758. Ten species, 3 of which are new, were found in small mammals: Trichostrongylus colubriformis (Giles, 1892) in Hystrix indica Kerr, 1792; Tenorastrongylus josephi n. sp. in Mus musculus L., 1758; Nippostrongylus brasiliensis (Travassos, 1914) in Rattus norvegicus Berk, 1796 and Rattus rattus L., 1758; Nippostrongylus witenbergi Greenberg, 1972, in Nesokia indica Gray et Hardw., 1832; Heligmonina nevoi n. sp. in Spalax ehrenbergi, Nehring, 1898; Boreostrongylus seurati (Travassos et Darriba, 1929) in Gerbillus allenbyi Thomas, 1918, G. pyramidum Geoffrey, 1825, G. (Dipodillus) dasyurus, Meriones sacramenti Thomas, 1922 and M. tristrami Thomas, 1892; Boreostrongylus minutus (Dujardin, 1845) in Microtus guentheri Danford et Alsen, 1880; Heligmosomoides polygyrus polygyrus (Dujardin, 1845) in Apodemus mystacinus Danf. et Alst., 1877 and A. sylvaticus L., 1758; Suncinema witenbergi n. sp. in Crocidura russula Herm., 1780. Ecologic and zoogeographic relationships are discussed.


Effect of apple polyphenols on vascular oxidative stress and endothelium function: a translational study.
We aimed examining apple polyphenols' effect on uricemia and endothelial function in a sample of overweight subjects. This was a two-phased study. In vitro experiment aimed to evaluate apple polyphenols' ability to lower uric acid in comparison with allopurinol. In vivo study consisted in a randomized, double-blind, parallel placebo-controlled clinical trial involving 62 overweight volunteers with suboptimal values of fasting plasma glucose (100 mg/dL≤FPG≤125 mg/dL), randomized to 300 mg apple polyphenols or placebo for 8 weeks. Apple polyphenols extract inhibited xanthine oxidase activity, with an IC50 = 130 ± 30 ng/mL; reducing uric acid production with an IC50 = 154 ± 28 ng/mL. During the trial, after the first 4 weeks of treatment, FPG decreased in the active treated group (-6.1%, p < 0.05), while no significant changes were observed regarding the other hematochemistry parameters. After 4 more weeks of treatment, active-treated patients had an improvement in FPG compared to baseline (-10.3%, p < 0,001) and the placebo group (p < 0,001). Uric acid (-14.0%, p < 0.05 versus baseline; p < 0.05 versus placebo) and endothelial reactivity (0.24±0.09, p = 0.009 versus baseline; p < 0.05 versus placebo) significantly improved too. In vivo, apple polyphenols extract has a positive effect on vascular oxidative stress and endothelium function and reduce FPG and uric acid by inhibiting xanthine oxidase, as our In vitro experiment attests.


Reclassification of the polyphyletic genus Prosthecomicrobium to form two novel genera, Vasilyevaea gen. nov. and Bauldia gen. nov. with four new combinations: Vasilyevaea enhydra comb. nov., Vasilyevaea mishustinii comb. nov., Bauldia consociata comb. nov. and Bauldia litoralis comb. nov.
Species of the genus Prosthecomicrobium are noted for their numerous cellular appendages or prosthecae that extend from the cells. This investigation confirms that the genus is polyphyletic based on an extensive analysis of the 16S rRNA gene sequences of several named species of the genus. The analyses indicate that some Prosthecomicrobium species are more closely related to non-prosthecate genera, including Devosia, Labrenzia, Blastochloris, Methylosinus, Mesorhizobium and Kaistia, than they are to other species of the genus Prosthecomicrobium. For this reason, two of the Prosthecomicrobium clades which are polyphyletic with the type species, Prosthecomicrobium pneumaticum, are renamed as new genera. The currently named species Prosthecomicrobium enhydrum, Prosthecomicrobium mishustinii, Prosthecomicrobium consociatum and Prosthecomicrobium litoralum are reclassified in two new genera, Vasilyevaea gen. nov. and Bauldia gen. nov. with four new combinations: Vasilyevaea enhydra comb. nov. (the type species) and Vasilyevaea mishustinii comb. nov., and Bauldia consociata comb. nov. and Bauldia litoralis comb. nov. (the type species). The type strain of Vasilyevaea enhydra is strain 9b(T) (=ATCC 23634(T) =VKM B-1376(T)). The type strain of the other species in this genus is Vasilyevaea mishustinii strain 17(T) (=VKM B-2499(T) =CCM 7569(T)). The type strain of Bauldia litoralis is strain 524-16(T) (= NCIB 2233(T) =ATCC 35022(T)). The type strain of the other species in this genus is Bauldia consociata strain 11(T) (=VKM B-2498(T) =CCM 7594(T)).


Giant electrostrictive response in poly(vinylidene fluoride-hexafluoropropylene) copolymers.
Electrostrictive strains were measured in three different polymeric materials: a low modulus polyurethane elastomer, previously studied by Scheinbeim et al. (1994), and two higher modulus random copolymers of poly(vinylidene fluoride-hexafluoropropylene) [P(VDF-HFP)] with 5% and 15% HFP content. Measurements at increasing voltage (electric fields ranging from 0 to 60 MV/m) were taken using an air gap capacitance system and then converted to sample thickness. Copolymer samples with different thermal histories were compared, ice water quenched, air quenched, and slow cooled, for both compositions. The ice water-quenched 5% P(VDF-HFP) copolymer exhibited the highest strain response (>4%) with a dielectric constant of 13.9. The previously studied polyurethane elastomer exhibited the second highest strain response, >3%, with the lowest dielectric constant, 8.5. The ice water-quenched 15% HFP copolymer exhibited the lowest strain response among the three polymeric materials tested, /spl ap/3%, with a dielectric constant of 12.2. The strain energy density of the 5% HFP ice water-quenched copolymer, /sup 1///sub 2/ YS/sub m//sup 2/ (/sup 1///sub 2/ Young's modulus, Y, times the maximum electrostrictive strain, S/sub max/ squared), is the largest known for any semi-crystalline polymer: 0.88J/cm/sup 3/.


Comparison of reverse transcriptase assay with the Retro-Tek viral capture assay for detection of human immunodeficiency virus.
The reverse transcriptase (RT) assay for human immunodeficiency virus (HIV) is tedious, expensive, and nonspecific for HIV activity. Because the Retro-Tek viral capture assay (VCA) (Cellular Products, Inc., Buffalo, NY) is relatively quick, inexpensive, and specific for HIV antigens, we compared the sensitivity and specificity of the two assays in a blinded fashion to see if the VCA could replace the RT assay. Specifically, peripheral mononuclear cells were cocultured from 11 Western blot-positive acquired immunodeficiency syndrome (AIDS) patients. The culture supernatant fluids were tested every 4-7 days for at least 28 days by VCA for HIV antigens, and by RT assay for retrovirus activity. Ten seronegative healthy donors with no risk factors were also cocultured and tested. Seven (64%) of 11 AIDS patients were positive by VCA and confirmed by RT assay in each instance. Concordance between VCA and RT assay was 100% in each patient. Time-to-positive detection was 7-28 days for both assays. Once a culture became positive by either assay, subsequent culture supernatant fluids remained positive by both assays until the culture was discarded, usually at day 28. The ten healthy seronegative donors were negative by both assays. These results suggest that the VCA is preferable to the RT assay for detection of HIV.


[The origins of the basic healthcare system in Brazil: the District System of Sanitation Administration].
There exists an interaction between multiple issues involving policy making, the building of knowledge and the implementation of practices in the health sector, which results in the particular way health services are provided in different historical contexts. The emergence and consolidation of sanitation organization was the result of a political process based on an idea of meeting the needs perceived in a given historical context. The historical course taken by the basic healthcare system in Brazil is analyzed from the perspective of its organizational and welfare principles, its expansion in physical terms, and its function within the public health system between 1918 and 1942. The article seeks to describe in detail the antecedents and initiatives taken in the establishment of a district system of sanitation administration, first in Rio de Janeiro and later across Brazil, which was a precursor of the basic healthcare system in Brazil.


Minimally invasive cardiac output technologies in the ICU: putting it all together.
Haemodynamic monitoring is a cornerstone in the diagnosis and evaluation of treatment in critically ill patients in circulatory distress. The interest in using minimally invasive cardiac output monitors is growing. The purpose of this review is to discuss the currently available devices to provide an overview of their validation studies in order to answer the question whether these devices are ready for implementation in clinical practice. Current evidence shows that minimally invasive cardiac output monitoring devices are not yet interchangeable with (trans)pulmonary thermodilution in measuring cardiac output. However, validation studies are generally single centre, are based on small sample sizes in heterogeneous groups, and differ in the statistical methods used. Minimally and noninvasive monitoring devices may not be sufficiently accurate to replace (trans)pulmonary thermodilution in estimating cardiac output. The current paradigm shift to explore trending ability rather than investigating agreement of absolute values alone is to be applauded. Future research should focus on the effectiveness of these devices in the context of (functional) haemodynamic monitoring before adoption into clinical practice can be recommended.


App-based assessment of memory functions in patients after transfemoral aortic valve replacement.
Transfemoral aortic valve replacement (TAVR) is the standard treatment for elderly patients with aortic valve stenosis. Although safe and well-established, there is a risk of intraprocedural hemodynamic instability and silent cerebral embolism, which can lead to a decline in neurocognitive function and dementia. In clinical practice, comprehensive cognitive testing is difficult to perform. AI-assisted digital applications may help to optimize diagnosis and monitoring. Neurocognitive function was assessed by validated psychometric tests using "∆elta -App", which uses artificial intelligence and computational linguistic methods for extraction and analysis. Memory function was assessed using the 'Consortium to Establish a Registry for Alzheimer's Disease' (CERAD) word list and digit span task (DST) before TAVR and before hospital discharge. The study is registered in the German Register of Clinical Trials (https://drks.de/search/de/trial/DRKS00020813). From October 2020 until March 2022, 141 patients were enrolled at University Hospital Heart Centre Brandenburg. Mean age was 81 ± 6 years, 42.6% were women. Time between the pre- and post-interventional test was on average 6 ± 3 days. Memory function before TAVR was found to be below average in relation to age and educational level. The pre-post TAVR comparison showed significant improvements in the wordlist repeat, P < 0.001 and wordlist recall test of CERAD, P < 0.001. There were no changes in the digital span test. Despite impaired preoperative memory function before TAVR, no global negative effect on memory function after TVAR was detected. The improvements shown in the word list test should be interpreted as usual learning effects in this task.


Diet Composition, Anthropometrics, and Mortality Risk.
While overeating is considered a cause of the obesity epidemic as quantified by body mass index (BMI), the association of diet with a body shape index (ABSI) and hip index (HI), which are transformations of waist and hip circumference that are independent of BMI and which predict mortality risk, is poorly known. We used data from the Atherosclerosis Risk in Communities (ARIC) study of about 15,000 middle-aged adults to investigate associations between macronutrient intake (energy, carbohydrate, protein, and fat, the latter two divided into plant and animal sources, all based on self-reported food frequency) with anthropometric indices (BMI, ABSI, and HI). We also analyzed the association of diet and anthropometrics with death rate during approximately 30 years of follow-up. High intake of energy and animal fat and protein was generally associated with higher ABSI and lower HI at baseline, as well as greater mortality hazard. BMI was also positively linked with animal fat and protein intake. In contrast, higher intake of carbohydrates and plant fat and protein was associated with lower ABSI and BMI, higher HI, and lower mortality hazard. For example, after adjustment for potential confounders, each standard deviation of additional plant fat intake (as a fraction of total energy) was associated with a 5% decrease in mortality rate, while animal fat intake was associated with a 5% mortality increase per standard deviation. The directions of the associations between diet and anthropometrics are consistent with those found between anthropometrics and mortality without reference to diet.


Did My Brain Implant Make Me Do It? Questions Raised by DBS Regarding Psychological Continuity, Responsibility for Action and Mental Competence.
Deep brain stimulation (DBS) is a well-accepted treatment for movement disorders and is currently explored as a treatment option for various neurological and psychiatric disorders. Several case studies suggest that DBS may, in some patients, influence mental states critical to personality to such an extent that it affects an individual's personal identity, i.e. the experience of psychological continuity, of persisting through time as the same person. Without questioning the usefulness of DBS as a treatment option for various serious and treatment refractory conditions, the potential of disruptions of psychological continuity raises a number of ethical and legal questions. An important question is that of legal responsibility if DBS induced changes in a patient's personality result in damage caused by undesirable or even deviant behavior. Disruptions in psychological continuity can in some cases also have an effect on an individual's mental competence. This capacity is necessary in order to obtain informed consent to start, continue or stop treatment, and it is therefore not only important from an ethical point of view but also has legal consequences. Taking the existing literature and the Dutch legal system as a starting point, the present paper discusses the implications of DBS induced disruptions in psychological continuity for a patient's responsibility for action and competence of decision and raises a number of questions that need further research.


A Versatile Framework for Simulating the Dynamic Mechanical Structure of Cytoskeletal Networks.
Computer simulations can aid in understanding how collective materials properties emerge from interactions between simple constituents. Here, we introduce a coarse-grained model that enables simulation of networks of actin filaments, myosin motors, and cross-linking proteins at biologically relevant time and length scales. We demonstrate that the model qualitatively and quantitatively captures a suite of trends observed experimentally, including the statistics of filament fluctuations, and mechanical responses to shear, motor motilities, and network rearrangements. We use the simulation to predict the viscoelastic scaling behavior of cross-linked actin networks, characterize the trajectories of actin in a myosin motility assay, and develop order parameters to measure contractility of a simulated actin network. The model can thus serve as a platform for interpretation and design of cytoskeletal materials experiments, as well as for further development of simulations incorporating active elements.


Efficacy and mechanism of Shenqi Compound in inhibiting diabetic vascular calcification.
Shenqi Compound (SQC) has been used in clinic for several decades in the prevention and treatment of diabetes and its complications. But this is merely a heritage of experience. The primary aim of this study is to scientifically validate the therapeutic effects of SQC on diabetic vascular calcification (DVC) in an animal model and, simultaneously, uncover its potential underlying mechanisms. Spontaneous diabetic rat- Goto Kakizaki (GK) rats were selected for rat modeling. We meticulously designed three distinct groups: a control group, a model group, and an SQC treatment group to rigorously evaluate the influence of SQC. Utilizing a comprehensive approach that encompassed methods such as pathological staining, western blot analysis, qRT-PCR, and RNA sequencing, we thoroughly investigated the therapeutic advantages and the underlying mechanistic pathways associated with SQC in the treatment of DVC. The findings from this investigation have unveiled the extraordinary efficacy of SQC treatment in significantly mitigating DVC. The underlying mechanisms driving this effect encompass multifaceted facets, including the restoration of aberrant glucose and lipid metabolism, the prevention of phenotypic transformation of vascular smooth muscle cells (VSMCs) into osteogenic-like states, the subsequent inhibition of cell apoptosis, the modulation of inflammation responses, the remodeling of the extracellular matrix (ECM), and the activation of the Hippo-YAP signaling pathway. Collectively, these mechanisms lead to the dissolution of deposited calcium salts, ultimately achieving the desired inhibition of DVC. Our study has provided compelling and robust evidence of the remarkable efficacy of SQC treatment in significantly reducing DVC. This reduction is attributed to a multifaceted interplay of mechanisms, each playing a crucial role in the observed therapeutic effects. Notably, our findings illuminate prospective directions for further research and potential clinical applications in the field of cardiovascular health.


Levels of antibodies to microorganisms implicated in atherosclerosis and of C-reactive protein among atomic bomb survivors.
Although it has been suggested that cardiovascular disease incidence is increased among atomic bomb survivors, the existence of a causal relationship between radiation exposure and atherosclerosis is unclear. Microbial infections, including those caused by Chlamydia pneumoniae, Helicobacter pylori and cytomegalovirus, have recently been implicated in atherosclerosis. Since immune function is somewhat impaired among atomic bomb survivors, their immune defense against such infections might be diminished. To investigate this possibility, we measured antibody levels to the above microorganisms in the sera of survivors. We found that the levels of IgG and IgA antibodies to Chlamydia pneumoniae decreased significantly with radiation dose, whereas the levels of IgG antibodies to Helicobacter pylori or cytomegalovirus remained unchanged. The inflammation marker C-reactive protein was significantly and positively associated with level of antibodies to Chlamydia pneumoniae only in heavily exposed (>or=1000 mGy) survivors. These results may suggest that among atomic bomb survivors, immune response to Chlamydia pneumoniae is diminished and chronic inflammatory reactions related to Chlamydia pneumoniae infection are present.


Functional Analysis of the Role of Toxoplasma gondii Nucleoside Triphosphate Hydrolases I and II in Acute Mouse Virulence and Immune Suppression.
Bioluminescent reporter assays have been widely used to study the effect of Toxoplasma gondii on host gene expression. In the present study, we extend these studies by engineering novel reporter cell lines containing a gamma-activated sequence (GAS) element driving firefly luciferase (FLUC). In RAW264.7 macrophages, T. gondii type I strain (GT1) infection blocked interferon gamma (IFN-γ)-induced FLUC activity to a significantly greater extent than infection by type II (ME49) and type III (CTG) strains. Quantitative trait locus (QTL) analysis of progeny from a prior genetic cross identified a genomic region on chromosome XII that correlated with the observed strain-dependent phenotype. This QTL region contains two isoforms of the T. gondii enzyme nucleoside triphosphate hydrolase (NTPase) that were the prime candidates for mediating the observed strain-specific effect. Using reverse genetic analysis we show that deletion of NTPase I from a type I strain (RH) background restored the higher luciferase levels seen in the type II (ME49) strain. Rather than an effect on IFN-γ-dependent transcription, our data suggest that NTPase I was responsible for the strain-dependent difference in FLUC activity due to hydrolysis of ATP. We further show that NTPases I and II were not essential for tachyzoite growth in vitro or virulence in mice. Our study reveals that although T. gondii NTPases are not essential for immune evasion, they can affect ATP-dependent reporters. Importantly, this limitation was overcome using an ATP-independent Gaussia luciferase, which provides a more appropriate reporter for use with T. gondii infection studies.


[Women's vulnerability to alcohol and its impact on health].
At the same level of consumption as men, specific vulnerabilities often expose women to the more rapid onset of more serious illnesses (cardiovascular and liver diseases, cancers, brain and cognitive damage, sleep disorders, risk of accidents, etc.). This worrying fact is still little known by the general population. Special prevention measures are needed, such as dedicated campaigns for women, specific guidelines for lower-risk drinking, systematic early detection of risky drinking among women, and brief intervention in the event of problem drinking.


Sleep Duration Trajectories and Body Composition in Adolescents: Prospective Birth Cohort Study.
We aimed to estimate the association between sleep duration trajectories and body composition in adolescents. We used data from participants of the 1993 Pelotas (Brazil) Birth Cohort Study who were later followed up at age 18 years (response rate of 81.3%). At the time, 3974 adolescents had complete data on body composition, which was assessed by air displacement plethysmography. Sleep duration was self-reported by participants at ages 11 and 18 years. Analyses were sex-stratified. The mean sleep duration at 11 years was 9.7 (SD 1.4) and 8.4 (SD 1.9) at 18 years. Sleep duration was dichotomized as inadequate (<8 hours/day) or adequate (≥8 hours/day). Mean body mass, fat mass, and fat-free mass indices at 18 years were 23.4 kg/m2 (SD 4.5), 6.1 kg/m2 (SD 3.9) and 17.3 kg/m2 (SD 2.5), respectively. Girls who reported inadequate sleep duration at 11 years of age, but adequate sleep duration at 18, on average experienced an increase in body mass index (β = 0.39 z-scores; 95% CI 0.13, 0.65), fat mass index (β = 0.30 z-scores; 95% CI 0.07, 0.53), and fat-free mass index (β = 0.24 z-scores; 95% CI 0.08, 0.39) compared to those who had adequate sleep duration at both time points. The results suggest that changes in sleep duration across adolescence may impact body composition in later adolescence and that this may differ by sex.


Toward a treaty on safety and cost-effectiveness of pharmaceuticals and medical devices: enhancing an endangered global public good.
Expert evaluations of the safety, efficacy and cost-effectiveness of pharmaceutical and medical devices, prior to marketing approval or reimbursement listing, collectively represent a globally important public good. The scientific processes involved play a major role in protecting the public from product risks such as unintended or adverse events, sub-standard production and unnecessary burdens on individual and governmental healthcare budgets. Most States now have an increasing policy interest in this area, though institutional arrangements, particularly in the area of cost-effectiveness analysis of medical devices, are not uniformly advanced and are fragile in the face of opposing multinational industry pressure to recoup investment and maintain profit margins. This paper examines the possibility, in this context, of States commencing negotiations toward bilateral trade agreement provisions, and ultimately perhaps a multilateral Treaty, on safety, efficacy and cost-effectiveness analysis of pharmaceuticals and medical devices. Such obligations may robustly facilitate a conceptually interlinked, but endangered, global public good, without compromising the capacity of intellectual property laws to facilitate local product innovations.


Self-assembly and structure of interconverting multinuclear inorganic arrays: a.
Coordination of the pentatopic ligand 3 with AgI leads to the simultaneous self-assembly of two polynuclear architectures: a [4 x 5] grid-type species 10 and a quadruple-helicate 11, which contain twenty and ten silver ions. respectively. Their structures have been established by X-ray diffraction analysis of the crystals obtained as a mixture on crystallisation. Complex 10 contains two [2 x 5]-AgI10 rectangular subgrids located on opposite sides of an array of parallel ligands of 3 that are twisted into a transoid N=C-C=N arrangement around the central C-C bond; it may thus be formulated as a grid of grids: [2 x (2 x 5)]. Complex 11 is an inorganic quadruple helicate that consists of two sets of two parallel ligands of 3 connected by an array of ten silver ions. Both compounds 10 and 11 are novel types of polynuclear complexes that are composed of two subunits. Their formation points to the possibility of generating specific arrays of metal ions by self-assembly, involving, in particular, a combination of subunits within the overall entity. They represent organised patterns of ion dots of special significance in view of their formal relationship to quantum dots.


[Correlational study among anger, perceived stress and mental health status in middle aged women].
This study was to identify the relationships of trait anger, mode of anger expression, and perceived stress to mental health status in middle aged women. The subjects were 157 middle aged women from 40s to 60s who lived in Seoul. Data was collected by questionnaire surveys using the convenience sampling. The instruments used for this study were Spielberger's trait anger scale and anger expression scale, Cohen, Kamarck, and Mermelstein's perceived stress and Derogatis's SCL-90-R. The collected data was analyzed using descriptive statistics, Pearson correlation coefficient, and Stepwise multiple regression with SAS/PC. The trait anger of middle aged women indicated a significantly positive correlation to perceived stress(r=.180, p=.023) and mental health status(r.=021, p=.014). Anger-in(r=.237, p<.05), and perceived stress(p=.461, p<.01) showed significantly positive correlation to mental health status. The most significant predictor influencing health status of middle aged women was perceived stress, and anger-in and the variance explained was 27%. These results suggested that middle aged women with high degree of trait anger is likely to be high in stress perception. Perceived stress and anger-in are major factors influencing mental health status.


Nonstoichiometry of nanocrystalline monoclinic silver sulfide.
Powders of silver sulfide have been synthesized by chemical bath deposition from aqueous solutions of silver nitrate and sodium sulfide in the presence of sodium citrate or EDTA-H2Na2. Colloid solutions have been prepared by a chemical condensation method from the same aqueous solutions. Synthesized silver sulfide nanopowders have a monoclinic (space group P21/c) acanthite-type structure but the occupancy of the metal sublattice sites by Ag atoms is smaller than 1. Unlike coarse-crystalline silver sulfide Ag2S, silver sulfide nanopowders with particles sizes of less than ∼50 nm are nonstoichiometric, contain vacant sites in the metal sublattice and have a composition of ∼Ag1.93S.


Solvent-free sonication of blackberries for the anthocyanin enrichment of juices obtained by pressing.
An ultrasound pretreatment was used to increase anthocyanins content in blackberry juice. Whole fruits were inserted into a glass vessel without contact with any solvent, sonicated in an ultrasonic bath, and then pressed with a manual juicer. The experimental design showed that 7 min at 65% of ultrasound amplitude increased the anthocyanin content in juices from 31 to 56% for BRS Xingu, Guarani, and Xavante cultivars. Two major anthocyanins, cyanidin-3-glucoside and cyanidin-3-rutinoside were found in higher concentrations for sonicated fruits. Therefore, ultrasonic pretreatment of whole fruits increased the anthocyanins in blackberry juices using a simple, fast, and green approach.


A case of recurrent metastatic ameloblastoma and hypercalcaemia successfully treated with carboplatin and paclitaxel: long survival and prolonged stable disease.
We describe a case of recurrent metastatic malignant ameloblastoma to the lungs with hypercalcaemia in a 47-year-old man. The first lung metastasis was resected nine years after the initial primary, and the tumour recurred with extensive pulmonary metastases 21 years after the primary tumour was resected. This case presented with malignancy-associated hypercalcaemia, likely due to paraneoplastic syndrome, which is exceedingly unusual in association with malignant ameloblastoma. He was successfully treated with carboplatin/paclitaxel and showed the longest survival and stable disease, from the diagnosis of recurrent metastasis, recorded as a case report. This regimen is reasonably well tolerated and can be repeated safely.


Model-based analysis supports interglacial refugia over long-dispersal events in the diversification of two South American cactus species.
Pilosocereus machrisii and P. aurisetus are cactus species within the P. aurisetus complex, a group of eight cacti that are restricted to rocky habitats within the Neotropical savannas of eastern South America. Previous studies have suggested that diversification within this complex was driven by distributional fragmentation, isolation leading to allopatric differentiation, and secondary contact among divergent lineages. These events have been associated with Quaternary climatic cycles, leading to the hypothesis that the xerophytic vegetation patches which presently harbor these populations operate as refugia during the current interglacial. However, owing to limitations of the standard phylogeographic approaches used in these studies, this hypothesis was not explicitly tested. Here we use Approximate Bayesian Computation to refine the previous inferences and test the role of different events in the diversification of two species within P. aurisetus group. We used molecular data from chloroplast DNA and simple sequence repeats loci of P. machrisii and P. aurisetus, the two species with broadest distribution in the complex, in order to test if the diversification in each species was driven mostly by vicariance or by long-dispersal events. We found that both species were affected primarily by vicariance, with a refuge model as the most likely scenario for P. aurisetus and a soft vicariance scenario most probable for P. machrisii. These results emphasize the importance of distributional fragmentation in these species, and add support to the hypothesis of long-term isolation in interglacial refugia previously proposed for the P. aurisetus species complex diversification.


Hyperhomocysteinemia and thrombosis: acquired conditions.
Hyperhomocysteinemia is a condition which, in the absence of kidney disease, indicates a disrupted sulfur amino acid metabolism, either because of vitamin (folate, B12 and B6) deficiency or a genetic defect. Epidemiological evidence suggests that mild hyperhomocysteinemia is associated with increased risk of arteriosclerotic disease and stroke. The relationship between hyperhomocysteinemia and thrombosis has been investigated in 10 studies involving a total of 1200 patients and 1200 controls. Eight of these studies demonstrated positive association with odds ratios that ranged from 2 to 13. This association was enhanced by including a methionine loading test. There is some evidence which suggests that hyperhomocysteinemia and APC resistance have a synergistic effect on the onset of thrombotic disease. Studies on the mechanism that underlies the relationship between thrombosis and hyperhomocysteinemia used non-physiologically high levels of homocysteine, rendering the data doubtful as to their patho-physiological relevance.


[Analgesics, antipyretics and non-steroidal anti-inflammatory drugs in pediatric prescriptions].
The use of analgesic, antipyretic and non-steroidal anti-inflammatory drugs by children more often than not neither have the approval of regulatory agencies nor the endorsement of scientific evidence. Pediatric prescriptions can be influenced by factors that do not promote the rational use of drugs by this category. The objective of this study was to evaluate the use of analgesic, antipyretic and non-steroidal anti-inflammatory drugs in children, considering the public (SUS) and private (N-SUS) sectors. The sample comprised 150 prescriptions (101 SUS and 49 Non-SUS) followed by interviews with the caregivers in eighteen locations (nine private drugstores and nine units of the Unified Health System (SUS). The drugs were prescribed appropriately, by age group, only in 21.8% (SUS) and 29.6% (Non-SUS) prescriptions. Over 95% of prescription, regardless of source, did not meet the established criteria for evaluation of their rational use, with dosage, frequency and duration of treatment errors. The analysis of prescriptions for analgesic, antipyretic and non-steroidal anti-inflammatory drugs for children revealed no significant differences between the public and private sectors.


Cell cycle arrest mediated by a pyridopyrimidine is not abrogated by over-expression of Bcl-2 and cyclin D1.
Inhibition of cyclin dependent kinases (Cdks) is of pivotal importance in tumor cell biology as these kinases are the drivers of cell proliferation. This inhibition can be achieved either by naturally occurring biological proteins or by small molecule compounds. They cause cell cycle arrest and/or apoptosis depending upon the specificity and efficacy of the inhibitor in question. We have reported earlier that specific pyridopyrimidines (novel Cdk inhibitors) cause cell cycle arrest in mink lung epithelial cells and the arrest is abrogated by over-expression of Cdk4. In contrast, we show here that one of these inhibitors effectively maintains cell cycle arrest in a leukemic or a breast cancer cell line even after the respective cells over-express an oncogene, either Bcl-2 or cyclin D1. However, in the leukemic cells, Bcl-2 over-expression suppresses apoptosis induced by the pyridopyrimidine. Thus, novel Cdk inhibitors can prove to be useful chemical genetics tools for understanding the underlying mechanisms of growth arrest and/or apoptosis in normal versus tumor cells. This could also lead to the development of improved inhibitors of cell proliferation.


Ranitidine protects against gastroduodenal mucosal damage associated with chronic aspirin therapy.
A randomized, double-blind, placebo-controlled study examined whether concomitant administration of ranitidine could protect against the gastroduodenal mucosal damage associated with long-term aspirin therapy in healthy men. Twenty-four subjects received ranitidine (150 mg twice daily) plus aspirin (650 mg four times daily), and 19 received placebo twice daily plus aspirin (650 mg four times daily) for four weeks. Gastric injury and duodenal injury were assessed separately according to a numerical rating scale for incidence and severity of lesions observed during endoscopic examinations at baseline and after four weeks of treatment. The ranitidine/aspirin group had significantly less mucosal damage in the stomach and duodenum than the placebo/aspirin group. Mean serum salicylate levels were similar between treatment groups after two and four weeks of aspirin therapy. Therefore, the protective effect of ranitidine was achieved with no compromise in salicylate absorption.


The effects of subchronic methidathion toxicity on rat liver: role of antioxidant vitamins C and E.
Methidathion (MD) phosphorodithioic acid S-[(5-methoxy-2-oxo-1,3,4-thiadiazol-3(2H)-yl)methyl] O,O-dimethyl ester is the organophosphate insecticide (OPI) most commonly used worldwide in the pest control of crops. Subchronic MD exposure was evaluated for its effects on lipid peroxidation, the serum activities of cholinesterase (ChE), and enzymes concerning liver damage, and the protective effects of combination of vitamins E and C in albino rats. Additionally, the histopathological changes in liver tissue were examined. Experimental groups were as follows: control group; a group treated with 5 mg/kg body weight MD (MD group); and a group treated with 5 mg/kg body wight MD plus vitamin E plus vitamin C (MD+AO group). The MD and MD+AO groups were treated orally with MD on five days a week for 4 weeks. The serum activities of cholinesterase (ChE), alanine transferase (ALT), aspartate amiotransferase (AST), lactate dehydrogenase (LDH), gamma-glutamyltransferase (GGT), alkaline phosphatase (ALP), and the concentration of malondialdehyde (MDA) and liver histopathology were studied. In serum samples, MD significantly increased MDA concentration and ALP, AST, GGT, LDH activities but decreased the ALT and ChE activities. In the MD+AO group, MDA level and ALP, AST, LDH activities were significantly decreased and ChE activity was increased compared to the MD group. Histopathological changes found in liver tissue of rats treated with MD included were infiltration with mononuclear cells in all portal areas, sinusoidal dilatation, and focal microvesicular steatosis and hydropic degenerations in parenchymal tissue. The severity of these lesions was reduced by administration of vitamins. From these results, it can be concluded that subchronic MD causes liver damage, and lipid peroxidation may be a molecular mechanism involved in MD-induced toxicity. Furthermore, the combination of vitamins E and C can reduce the toxic effects of MD on liver tissue of rats.


Temporal landscape of mitochondrial proteostasis governed by the UPRmt.
Breakdown of mitochondrial proteostasis activates quality control pathways including the mitochondrial unfolded protein response (UPRmt) and PINK1/Parkin mitophagy. However, beyond the up-regulation of chaperones and proteases, we have a limited understanding of how the UPRmt remodels and restores damaged mitochondrial proteomes. Here, we have developed a functional proteomics framework, termed MitoPQ (Mitochondrial Proteostasis Quantification), to dissect the UPRmt's role in maintaining proteostasis during stress. We find essential roles for the UPRmt in both protecting and repairing proteostasis, with oxidative phosphorylation metabolism being a central target of the UPRmt. Transcriptome analyses together with MitoPQ reveal that UPRmt transcription factors drive independent signaling arms that act in concert to maintain proteostasis. Unidirectional interplay between the UPRmt and PINK1/Parkin mitophagy was found to promote oxidative phosphorylation recovery when the UPRmt failed. Collectively, this study defines the network of proteostasis mediated by the UPRmt and highlights the value of functional proteomics in decoding stressed proteomes.