Anaplastic thyroid carcinoma with rhabdomyoblastic differentiation: a case report with a good clinical outcome.
Anaplastic thyroid carcinoma is a rare and highly malignant disease. Usually, this type of tumor is irresectable, and almost all patients die within 1 year after diagnosis. We present a case of anaplastic thyroid carcinoma with rhabdomyoblastic differentiation and good therapeutic outcome. A 76-year-old female was referred to our hospital with a growing, painless neck mass which existed for 3 months. Biopsy of the mass showed microscopically and immunohistochemically a follicular (Hürthle cell) carcinoma of the thyroid, dedifferentiated to an anaplastic carcinoma with divergent differentiation along rhabdomyoblastic cell lines. The patient underwent a total thyroidectomy with additional lymph node dissection, followed by two episodes of 150 mC I(131) therapy and external radiotherapy. After a follow-up of 3 years, the patient still remains in a good condition without any signs of recurrent disease. Other cases of rhabdomyoblastic and rhabdoid anaplastic thyroid carcinomas have been described. Both types of carcinoma are associated with an aggressive clinical course. In our case, the patient is still alive without evidence of disease 3 years after primary therapy. The good clinical outcome of our patient suggests that surgical resection, radiotherapy, and I-131 ablation therapy with curative intent seems to be an adequate treatment option in patients with anaplastic thyroid carcinoma with rhabdoid and rhabdomyoblastic differentiation.


Facile synthesis of methyl alpha- and beta-D-[6-(3)H]galactofuranosides from D-galacturonic acid. Substrates for the detection of galactofuranosidases.
Galactofuranose metabolism is a good target for the development of novel chemotherapeutic agents for the treatment of some microbial infections. A simple procedure for the synthesis of methyl (methyl alpha,beta-D-galactopyranosid)uronate followed by NaB(3)H(4) reduction gave a straightforward access to radiolabeled substrates for galactofuranosidases.


The effect of semen processing on sperm morphology.
Semen samples were obtained from 28 infertile men referred for AIH. The percentage morphologically normal sperm was assessed on Papanicolaou stained smears before and after semen processing. The percentage of normal sperm increased significantly (p less than 0.005). It would seem that the semen processing procedure increased the number of morphologically normal sperm, which could theoretically improve the results of AIH.


Candida albicans translocation across the gut mucosa following burn injury.
Normal guinea pigs were challenged intragastrically with Candida albicans 1 hr prior to a 30 or 50% flame burn to determine if burn injury increased translocation of the yeasts across gut mucosa. Tissues were harvested between 3 and 24 hr postburn and cultured on Sabouraud dextrose agar. Control animals (no yeast challenge) showed no yeast in intestinal homogenates or in the mesenteric lymph nodes (MLN). At a dose of 1 X 10(9) yeasts, they did not escape from the gut lumen, with either a 30 or 50% burn. At a dose of 2 to 4 X 10(10) organisms, they translocated to the MLN in 92% of the 50%-burned animals (P less than 0.001), 75% of the 30%-burned animals (P less than 0.05), and 12.5% of unburned animals. The ileal mucosa appeared to be the most susceptible site for yeast invasion. To observe the penetration through the gut mucosa and/or translocation to other tissues, yeasts were labeled with biotin before administration, and tissues were stained with avidin-peroxidase diaminobenzidine sequence. With biotinylated yeasts, phagocytized organisms were observed in large numbers in the lamina propria and mesenteric lymph nodes but they were not viable upon culture. Toluidine blue staining of semithin sections revealed that translocated yeasts were located selectively in the lymphoid follicles of the MLN, entrapped by macrophages.


Atropisomeric Hydrogen Bonding Control for CO2 Binding and Enhancement of Electrocatalytic Reduction at Iron Porphyrins.
The manipulation of the second coordination sphere for improving the electrocatalytic CO2 reduction has led to breakthroughs with hydrogen bonding, local proton source, or electrostatic effects. We have developed two atropisomers of an iron porphyrin complex with two urea functions acting as multiple hydrogen-bonding tweezers to lock the metal-bound CO2 in a similar fashion found in the carbon monoxide dehydrogenase (CODH) enzyme. The αα topological isomer with the two urea groups on the same side of the porphyrin provides a stronger binding affinity to tether the incoming CO2 in comparison to the αβ disposition. However, the electrocatalytic activity of the αβ atropisomer outperforms its congener with one of the highest reported turnover frequencies at low overpotential. The strong H/D kinetic isotope effect (KIE) observed for the αα system indicates the existence of a tight water hydrogen-bonding network for proton delivery which is disrupted by addition of an acid source. The small H/D KIE for the αβ isomer and the enhanced electrocatalytic performance on addition of stronger acid indicate the free access of protons to the bound CO2 on the opposite side of the urea arm.


GLP-1 agonist treatment: implications for diabetic retinopathy screening.
Rapid improvement in glycaemic control induced by GLP-1 agonist therapy could be yet another illustration of transient or permanent progression of diabetic retinopathy, similar to documented examples such as pregnancy and continuous subcutaneous insulin infusion. Specific guidelines would be needed to monitor this paradoxical phenomenon during treatment with GLP-1 agonists.


Rapid capillary gel electrophoresis of proteins.
The rapid separation of sodium dodecyl sulphate-protein complexes according to their molecular masses (M(r)) by capillary gel electrophoresis is described. Using commercial equipment, standard proteins with M(r) in the range 29,000-97,400 were resolved to the baseline in less than 2 min by utilizing a separation distance of 7 cm. A linear relationship between migration time and log M(r) was found and rapid determination of the molecular mass of light and heavy chains of human immunoglobulin G is reported. The results are compared with applications using longer separation distances, showing that rapid and efficient analysis and adequate resolution can be obtained by using short separation distances.


Gerbils exhibit stable open-arms exploration across repeated testing on the elevated plus-maze.
Repeated testing on the elevated plus-maze (EPM) leads rats and mice to avoid the open-arms of the apparatus. The effect of multiple exposures to the EPM on the behavioral profile of gerbils is unknown. In this study, young and middle-aged gerbils were exposed to the EPM and four retests were carried out 24, 48, 72 and 96h after the first trial in order to determine whether animals exhibited open-arms avoidance. In addition, groups of young and middle-aged gerbils were exposed to the EPM for 20-min followed by a 5-min retest trial 24h apart to analyze the effect of a prolonged exposure to the EPM on open-arms exploration during first trial and retest. Gerbils exhibited high exploration of open-arms during the first trial and progressive locomotor decrease across repeated testing. Unlike previous reports for rats and mice, young gerbils showed a stable open-arms exploration both across multiple exposures and during a prolonged exposure to EPM. Middle-aged gerbils also exhibited a stable open-arms exploration during retest prior to the 20-min test. Results suggest a reliable repeated test paradigm for the EPM using our proposed methodology for gerbils.


Experiences with Guillain-Barré syndrome in a pediatric intensive care unit.
During a 10-year period 16 children with acute Guillain-Barré syndrome were seen. Eleven were admitted to the Pediatric Intensive Care Unit, either because of difficulty of breathing and swallowing or because of symptoms of autonomic disturbance. Six patients were mechanically ventilated for a mean period of 17 days. Symptoms of autonomic disturbance were frequently seen especially in the mechanically ventilated patients. Two patients died because of cardiac arrhythmia. Methods of detecting patients at risk for cardiac dysrhythmia are suggested.


Determination of the archaeal and bacterial communities in two-phase and single-stage anaerobic systems by 454 pyrosequencing.
2-Phase anaerobic digestion (AD), where the acidogenic phase was operated at 2day hydraulic retention time (HRT) and the methanogenic phase at 10days HRT, had been evaluated to determine if it could provide higher organic reduction and methane production than the conventional single-stage AD (also operated at 12days HRT). 454 pyrosequencing was performed to determine and compare the microbial communities. The acidogenic reactor of the 2-phase system yielded a unique bacterial community of the lowest richness and diversity, while bacterial profiles of the methanogenic reactor closely followed the single-stage reactor. All reactors were predominated by hydrogenotrophic methanogens, mainly Methanolinea. Unusually, the acidogenic reactor contributed up to 24% of total methane production in the 2-phase system. This could be explained by the presence of Methanosarcina and Methanobrevibacter, and their activities could also help regulate reactor alkalinity during high loading conditions through carbon dioxide production. The enrichment of hydrolytic and acidogenic Porphyromonadaceae, Prevotellaceae, Ruminococcaceae and unclassified Bacteroidetes in the acidogenic reactor would have contributed to the improved sludge volatile solids degradation, and ultimately the overall 2-phase system's performance. Syntrophic acetogenic microorganisms were absent in the acidogenic reactor but present in the downstream methanogenic reactor, indicating the retention of various metabolic pathways also found in a single-stage system. The determination of key microorganisms further expands our understanding of the complex biological functions in AD process.


Protective effects of ascorbic acid, dl-alpha-tocopherol acetate, and sodium selenate on ethanol-induced liver damage of rats.
In this study, the effect of a combination of vitamin C (ascorbic acid), vitamin E (dl-alpha-tocopherol acetate), and selenium (sodium selenate) on ethanol-induced liver damage in rats was investigated, morphologically and biochemically. The ethanol-induced injury was produced by the administration of 1 mL of absolute ethanol to each rat. Animals received vitamin C (250 mg/kg), vitamin E (250 mg/kg), and selenium (0.5 mg/kg) (ViCESe) for 3 d 1 h prior to the administration of absolute ethanol. In the liver of the animals given ethanol, the degenerative changes such as extreme hyperemia, vacuolization in cells of portal areas, a dilation in sinusoids, mononuclear cell infiltration, a swelling in cisternae of granular endoplasmic reticulum and in mitochondrial cristae, an increase in smooth endoplasmic reticulum, many lipid vacuoles were observed both light and electron microscopically. A similar structure was usually distinguished when compared with control animals, in rats given ethanol + ViCESe. In this group, the findings indicating cellular damage were either not observed at all or were decreased. In the group administered ethanol, a reduction of the blood glutathione (GSH) level and increases in serum values of alanine aminotranserase (ALT), aspartate aminotransferase (AST), lactate dehydrogenase (LDH), alkaline phosphatase (ALP), and gamma-glutamyl transferase (GGT) activities were observed, whereas in the control group, the reverse was found to occur. On the other hand, in the group in which ethanol + ViCESe was administered, it was observed that the blood GSH value and serum ALP and ALT activities increased and serum AST, LDH, and GGT activities decreased. As a result, the present study indicates that ViCESe because of their antioxidant activity against ethanol damage have a protective effect on the liver.


Broadband high efficiency silicon nanowire arrays with radial diversity within diamond-like geometrical distribution for photovoltaic applications.
In this study we report novel silicon nanowire (SiNW) array structures that have near-unity absorption spectrum. The design of the new SiNW arrays is based on radial diversity of nanowires with periodic diamond-like array (DLA) structures. Different array structures are studied with a focus on two array structures: limited and broad diversity DLA structures. Numerical electromagnetic modeling is used to study the light-array interaction and to compute the optical properties of SiNW arrays. The proposed arrays show superior performance over other types of SiNW arrays. Significant enhancement of the array absorption is achieved over the entire solar spectrum of interest with significant reduction of the amount of material. The arrays show performance independent of angle of incidence up to 70 degrees, and polarization. The proposed arrays achieved ultimate efficiency as high as 39% with filling fraction as low as 19%.


Ocular surgery on patients receiving long-term warfarin therapy.
We analyzed data of 50 patients receiving long-term warfarin sodium therapy who underwent ocular surgery between 1982 and 1986. The frequency of hemorrhagic and thrombotic complications was compared in patients in whom anticoagulants were continued, those in whom the anticoagulants were discontinued in the perioperative period, and a group of matched control patients. There were six perioperative hemorrhagic complications in the warfarin-treated group (12%) compared to none in the control group. This difference was significant (P less than .03). However, no significant difference in hemorrhagic complications was seen between patients in whom warfarin sodium was continued and those in whom it was discontinued.


Integration of water collection and purification on cactus- and beetle-inspired eco-friendly superwettable materials.
Freshwater shortage has been a terrible threat for the sustainable progress and development of human society in 21st century. Inspired from natural creatures, harvesting water from atmosphere has been a feasible and effective method to alleviate water shortage crisis. However, the recent works related to water collection just focuses on how to optimize fog-harvesting manners and efficiencies, the safety and availability of collected water are always ignored. In this paper, we proposed a new strategy accessed to freshwater resources through combining water collection and purification together on eco-friendly superwettable material inspired by cactus spines and desert beetles. Six superhydrophilic wedge-shaped patterns prepared by P25 TiO2 nanoparticles (NPs) were constructed on candle soot@polydimethylsiloxane (CS@PDMS) superhydrophobic coating. The special superhydrophilic regions not only effectively captured water from foggy environment but generated Laplace pressure gradient to faster drive water away. The bioinspired material exhibited an efficient water collection rate (WCR) of 14.9 ± 0.2 mg min-1 cm-2, which was 5.3 and 2.5 times larger than that on uniformed superhydrophilic and superhydrophobic surfaces, respectively. Because of the existence of photocatalytic P25 NPs in wetting areas, the harvested wastewater containing nine kinds of pesticides (0.5 mg/L) could be purified in low concentrations (< 5%) under UV light (365 nm, 5.0 ± 0.6 mW cm-2). Ten zebrafishes were still alive in such purified water for 72 h, as a contrast, the same number of fishes would almost die in untreated harvested wastewater in just 7 h. This work indeed opens up a new sight to freshwater accessibility, aiming to a promising project for alleviating water shortage around the world.


Excess costs of medical care 1 and 8 years after diagnosis of diabetes: estimates from young and middle-aged incidence cohorts in Sweden.
To analyze the excess costs of medical care during the first decade after diabetes diagnosis, we surveyed two national incidence cohorts who contracted diabetes at age of 15-34 years and matched control groups from the general population of Sweden. Ninety percent of the diabetic subjects were on insulin treatment. Data on healthcare utilization and use of glucose lowering drugs and medical devices were collected via a questionnaire mailed to a recent cohort 1 year after diagnosis and a previously registered cohort 8 years after diagnosis. Costing was based on average national costs of hospital inpatient and out-patient care, an original study of daycare costs, and sales prices of the National Corporation of Swedish Pharmacies. One year after diabetes diagnosis, the annual excess costs of care were US$4743 among men and US$4976 among women (1997 prices). Hospital inpatient care accounted for more than 50% of the excess costs. Eight years after diagnosis, the excess costs were US$2010 among men and US$2734 among women. The higher costs for women were mainly related to hospital out-patient care, but also to more intensive self-monitoring. We conclude that diabetes in young and middle-aged people is a major economic challenge even before significant complications may have developed.


The RTS,S malaria vaccine: Current impact and foundation for the future.
The RTS,S vaccine has recently been recommended for implementation as a childhood vaccine in regions with moderate-to-high malaria transmission. We discuss mechanisms of vaccine protection and longevity, implementation considerations, and future research needed to increase the vaccine's health impact, including vaccine modifications for higher efficacy and longevity of protection.


Can chest high-resolution computed tomography findings diagnose pulmonary alveolar microlithiasis?
The present study was aimed at retrospectively reviewing high-resolution computed tomography (HRCT) findings in patients with pulmonary alveolar microlithiasis in order to evaluate the frequency of tomographic findings and their distribution in the lung parenchyma. Thirteen patients (9 females and 4 males; age, 9 to 59 years; mean age, 34.5 years) were included in the present study. The HRCT images were independently evaluated by two observers whose decisions were made by consensus. The inclusion criterion was the presence of abnormalities typical of pulmonary alveolar microlithiasis at HRCT, which precludes lung biopsy. However, in 6 cases lung biopsy was performed. Ground-glass opacities and small parenchymal nodules were the predominant tomographic findings, present in 100% of cases, followed by small subpleural nodules (92.3%), subpleural cysts (84.6%), subpleural linear calcifications (69.2%), crazy-paving pattern (69.2%), fissure nodularity (53.8%), calcification along interlobular septa (46.2%) and dense consolidation (46.2%). As regards distribution of the lesions, there was preferential involvement of the lower third of the lungs. No predominance of distribution in axial and anteroposterior directions was observed.


Distinct fungal plastisphere across different river functional zones: A watershed scale study.
Fungi not only play important roles in biogeochemical processes but also can form biofilm on plastic debris. However, knowledge of structure composition and spatiotemporal pattern of fungal plastisphere on different kinds of plastic debris in river with specific usages, known as river functional zones, is still missing. In this study, we investigated the spatial distribution of the fungal plastisphere across a complete urban river with different functional zones (drinking, farm irrigation, aquaculture, and tail lake). Our research was performed based on both field residual plastic debris collection and a 30-day field in situ incubation experiments. Our study revealed that plastic debris enriched distinct fungal communities (including pathogenic fungi) significantly different from the surrounding water. Tracking the source of the fungi colonized on plastic debris suggested that the fungal taxa colonized on the different kinds of plastic debris were not from the surrounding water. Human activities had considerable effects on the fungal community structure on plastic debris, and the plastisphere fungal community structure strikingly varied across different river functional zones. Plastisphere may be used as an indicator for fungi biogeography and pathogenic fungi pollution in river with different functional zones. These findings are essential for ecological risk assessment and management decisions for pollution control of plastic debris and maintaining ecological health.


Combined recirculation of the rat liver and kidney: studies with enalapril and enalaprilat.
Combined recirculation of the rat liver (L) and kidney (IPK) at 10 ml min-1 per organ (LK) was developed to examine the hepatorenal handling of the precursor-metabolite pair: [14C]-enalapril and [3H]enalaprilat. Loading doses followed by constant infusion of [14C]enalapril and preformed [3H]enalaprilat to the reservoirs of the IPK or the LK preparation was used to achieve steady state conditions. In both organs, enalapril was mostly metabolized to its dicarboxylic acid metabolite, enalaprilat, which was excreted unchanged. At steady state, the fractional excretion for [14C]enalapril (FE = 0.45 to 0.48) and preformed [3H]enalaprilat (FE[pmi] = 1.1) were constant and similar for both the IPK and LK. The additivity of clearance was demonstrated in the LK preparation, namely, the total clearance of enalapril was the sum of its hepatic and renal clearances. However, the apparent fractional excretion for formed [14C]enalaprilat, FE(mi) and the apparent urinary clearance were time-dependent and higher than the corresponding values for preformed [3H]enalaprilat in both the IPK and LK. The FE(mi) and urinary clearance values further differed between the IPK and LK. Biliary clearance of formed vs. preformed enalaprilat displayed the same discrepant trends as observed for FE(mi) vs. FE(pmi) for the LK. These observations on the time-dependent and variable excretory clearance (urinary or biliary) of the formed metabolite vs. the constant, and much reduced, excretory clearance of the preformed metabolite are due to dual contributions to formed metabolite excretion: the nascently formed, intracellular metabolite which immediately underwent excretion and the formed metabolite which reentered the circulation, behaved as a preformed species. When data for the IPK and LK preparations were modeled with a physiological model with parameters previously reported for the L and IPK, all data, including metabolite excretory clearances, were well predicted. Model simulations revealed that the apparent FE(mi) differed between the LK and IPK preparations when the liver was present as an additional metabolite formation organ; the apparent excretory (urinary or biliary) clearance of the formed metabolite was further modulated by the volume of distribution of the metabolite, which altered levels of the formed, circulating metabolite.


External validation and comparison of the scoring systems (S.T.O.N.E, GUY, CROES, S-ReSC) for predicting percutaneous nephrolithotomy outcomes for staghorn stones: A single center experience with 160 cases.
The aim of this study was validation and comparison of stone scoring systems (S.T.O.N.E, GUY, CROES, S-ReSC) used to predict postoperative stone-free status and complications after percutaneous nephrolithotomy (PCNL) for staghorn stones. A total of 160 patients who had staghorn renal stones and underwent PCNL between January 2012 and August 2015 were included in the current retrospective study. Guy, S.T.O.N.E., S-ReSC (Seoul National University Renal Stone Complexity) and CROES (Clinical Research Office of the Endourological Society) nephrolithometry scores were calculated for each patient, and their potential association with stone-free status, operative and fluoroscopy time, and length of hospital stay (LOS) were evaluated. Postoperative complications were graded according to the modified Clavien classification, and the correlation of scoring systems with postoperative complications was also investigated. The mean CROES, S.T.O.N.E, Guy and S-ReSC scores were 143.5 ± 33.6, 9.7 ± 1.6, 3.5 ± 0.5 and 6.2 ± 2.0 respectively. The overall stone-free rate was 59%. All scoring systems were significantly correlated with stone-free status in univariate analysis. However, Guy and S-ReSC scores were the only significant independent predictor in multivariate analysis. And all four nomograms failed to predict complication rates. Current study demonstrated that Guy and S-ReSC scoring systems could effectively predict postoperative stone-free status for staghorn stones. However all four scoring systems failed to predict complication rates.


Helix geometry of single stranded DNA 'A' and 'B' forms from minimum energy conformations of dimeric subunits.
Low energy conformations with dihedral angles similar to those occurring in fibers of the 'A' and 'B' forms of DNAs have been calculated for the deoxydinucleoside phosphates dApdA, dCpdC, dTpdT, dGpdG and dGpdC (1-3). These conformers have been used as building blocks for generating larger single stranded polymers, whose helical parameters we have calculated. We find that single stranded 'A' and 'B' form helices tend to be narrower and more tightly wound than the duplexes obtained in fibers (4,5). This is consistent with experimental observations on single stranded fibers of poly (rC) (6). We also find that the different sequences have different helix geometries. In addition, it is observed that large variations in helix geometry for a given sequence are achievable at little energetic cost.


Iron-functionalized Al-SBA-15 for benzene hydroxylation.
For the first time an ordered mesoporous silica (Fe-Al-SBA-15) with catalytically active isolated Fe surface species for the hydroxylation of benzene with nitrous oxide is prepared by introduction of Fe3+ in the synthesis gel of Al-SBA-15.


Cardiovascular risk in 26,008 European overweight children as established by a multicenter database.
Although the obesity epidemic is progressing in European children too, there is no consensus on the population-specific prevalence of comorbidities or efficient diagnostic strategies. Therefore, weight-related risk factors, their interrelationship, and association with biological parameters were assessed in a large group of overweight (OW) children, documented by an electronic database. Data of 26,008 children (age 12.6+/-2.9 years, 56% females) presented for OW (BMI >90th percentile) or obesity (>97th percentile) in 98 specialized centers were evaluated using a simple software (Adipositas Patienten Verlaufsbeobachtung (APV)) for standardized longitudinal documentation. After local anonymization, data were transmitted for central analysis including multiple logistic regression. A total of 5.9% of the children were normal weight, 41% obese (OB), and 37% extremely OB (>99.5th percentile, XXL; 41% of the girls). In 50%, at least one risk factor and in 11% a cluster of two were found, comprising increased blood pressure (BP): 35.4%, dyslipidemia: 32% (total cholesterol: 14.1%, low-density lipoprotein (LDL)-cholesterol: 15.8%, high-density lipoprotein (HDL)-cholesterol: 11.1%, triglycerides: 14.3%), impaired glucose tolerance (IGtT): 6.5% and suspicion of diabetes: 0.7%. The degree of OW was inversely associated with HDL-cholesterol and directly with clustered risk factors, impaired glucose metabolism, increased BP and triglycerides (odds ratios (ORs) XXL vs. normal=6.15, >10, 4.3, 3.0 and 2.5, respectively), but not with LDL-cholesterol. In a very large cohort of young Europeans risk factors for cardiovascular (CV) diseases are frequently found, related to the degree of OW and tend to cluster, thus a comprehensive screening is justified in all OW or OB children. Electronic patient documentation is feasible in a large obesity care network.


A common sequence motif determines the Cajal body-specific localization of box H/ACA scaRNAs.
Post-transcriptional synthesis of 2'-O-methylated nucleotides and pseudouridines in Sm spliceosomal small nuclear RNAs takes place in the nucleoplasmic Cajal bodies and it is directed by guide RNAs (scaRNAs) that are structurally and functionally indistinguishable from small nucleolar RNAs (snoRNAs) directing rRNA modification in the nucleolus. The scaRNAs are synthesized in the nucleoplasm and specifically targeted to Cajal bodies. Here, mutational analysis of the human U85 box C/D-H/ACA scaRNA, followed by in situ localization, demonstrates that box H/ACA scaRNAs share a common Cajal body-specific localization signal, the CAB box. Two copies of the evolutionarily conserved CAB consensus (UGAG) are located in the terminal loops of the 5' and 3' hairpins of the box H/ACA domains of mammalian, Drosophila and plant scaRNAs. Upon alteration of the CAB boxes, mutant scaRNAs accumulate in the nucleolus. In turn, authentic snoRNAs can be targeted into Cajal bodies by addition of exogenous CAB box motifs. Our results indicate that scaRNAs represent an ancient group of small nuclear RNAs which are localized to Cajal bodies by an evolutionarily conserved mechanism.


[Thromboembolic risk associated with use of angiogenesis inhibitors used for the treatment of cancers].
Among antiangiogenic agents, thalidomide is not the most potent nor the most specific even so when venous thromboembolic events have been reported with the prescription of thalidomide in multiple myeloma. This side effect has been related to the antiangiogenic effect of this immunomodulator. In keeping with this observation venous thromboembolic events have been reported in other indications of thalidomide and with thalidomide analogues (Lenalidomide and Actimid). The thrombotic side effects are mostly venous but arterial thrombotic events are also observed with the use of these molecules. With the other and more specific antiagiogenic agents an increase in thrombotic events are also observed. This increase was not immediately evident since the situation in which they are prescribed (metastatic cancers) are already characterized by a high rate of thrombotic events. The prothrombotic effect of antiangiogenic agents are probably linked to an effect on endothelium (decrease of antithrombotic activities and stimulation of a prothrombotuic state). The other sides effects of antiangiogenic agents (hemorrhages, hypertension, proteinuria, microangiotpahia, delay in scaring) are also probably related to endothelial effects. The prothrombotic effect of antoangiogenic agents appears as potentiating the prothrombotic conditions of the disease (myeloma, cancer) and the prothombotic effects of the associated treatments (chemotherapy, high dose corticosteroids, erythropoietin). The increased thrombotic risk linked to prescription of antiangiogenic agents and specially of thalidomide and analogues for multiple myeloma is such that it is recommended to associate a preventive antithrombotic treatment. Some efficacy has been reported with the use of aspirin, oral anticoagulant or low molecular weight heparin. No head to head comparative trial do not allow to prefer one strategy. From published data full dose oral anticoagulants appear to confer the highest hemorrhagic risk and perhaps low molecular weight heparin the best benefit-risk ratio.


A remarkable new Awas Löbl from southern China (Coleoptera, Staphylinidae, Pselaphinae).
A new distinctive species of the rare Oriental goniacerine genus Awas Löbl, Awas gigas sp. n., is described and illustrated, based on three males and fourteen females taken at the Daoyao Shan Natural Reserve in the southern Chinese province of Guangxi. All specimens were collected from colonies of the ant genus Pachycondyla F. Smith nesting in decomposing woods.


Acupuncture for the Treatment of Migraine: An Overview of Systematic Reviews.
Over the past few years, there have been many systematic reviews (SRs) and meta-analyses (MAs) used to assess the safety and efficacy of acupuncture in the treatment of migraine. Our aim is to assess the methodological and reporting quality of SRs/MAs and make an evaluation about the available evidence of the safety and efficacy of acupuncture in the treatment of migraine. Migraine is one of the most common primary headaches, with various symptoms, threatening human health. Acupuncture is a specific treatment of Traditional Chinese Medicine (TCM), and a validated non-pharmaceutical option as well, widely used in the treatment of migraine, and has gained remarkable therapeutic effect. An overview can evaluate research methods and evidence for SRs/MAs in evidence-based medicine, although there is much relevant research, it's still a hard work to synthesis all the evidence or to make robust conclusions, the variation in the methodological and quality evidence in such SRs/MAs play a significant role. For this overview, we searched six electronic databases from inception until 8 September 2022, and without languages restrictions, the results showed that, acupuncture as a more safety and more convenient therapeutic, and it has been shown to be effective in the treatment of migraine, that is worthy of clinical promotion. However, there are also some limitations because of the low-quality evidence of most of the studies. In conclusion, most included SRs/MAs suggested that acupuncture was more effective than the control group in the treatment of migraine. However, the quality evidence of most of the studies still needs to be improved.


Digital labeling for 3D histology: segmenting blood vessels without a vascular contrast agent using deep learning.
Recent advances in optical tissue clearing and three-dimensional (3D) fluorescence microscopy have enabled high resolution in situ imaging of intact tissues. Using simply prepared samples, we demonstrate here "digital labeling," a method to segment blood vessels in 3D volumes solely based on the autofluorescence signal and a nuclei stain (DAPI). We trained a deep-learning neural network based on the U-net architecture using a regression loss instead of a commonly used segmentation loss to achieve better detection of small vessels. We achieved high vessel detection accuracy and obtained accurate vascular morphometrics such as vessel length density and orientation. In the future, such digital labeling approach could easily be transferred to other biological structures.


Composition, structure and flavor mechanism of numbing substances in Chinese prickly ash in the genus Zanthoxylum: A review.
Chinese prickly ash is known for producing a typical pungent sensation in Sichuan Cuisine. Accumulating evidence suggest a series of health benefits and pharmacological effects associated with prickly ash. Therefore, a systematic analysis of the composition, structural properties, detection, and flavor mechanism of numbing substances is highly necessitated to address their future application. Sanshool-based unsaturated amides are the primary cause of tingling. The numbing substances have poor stability and are prone to oxidation and decomposition reactions due to their highly unsaturated conjugated diene structures. Pungent sensations evoked by different sanshools are distinct, which is attributed to different mechanisms of interaction with membrane ion channels (TRPV1, TRPA1, and KCNK). In this paper, the composition, structural properties (such as isomerization, oxidation), detection, and flavor mechanism of numbing substances of prickly ash were summarized. The prospective application and future research direction of numbing substances in the prickly ash industry were also proposed.


A Functional Screening Identifies a New Organic Selenium Compound Targeting Cancer Stem Cells: Role of c-Myc Transcription Activity Inhibition in Liver Cancer.
Cancer stem cells (CSCs) are reported to play essential roles in chemoresistance and metastasis. Pathways regulating CSC self-renewal and proliferation, such as Hedgehog, Notch, Wnt/β-catenin, TGF-β, and Myc, may be potential therapeutic targets. Here, a functional screening from the focused library with 365 compounds is performed by a step-by-step strategy. Among these candidate molecules, phenyl-2-pyrimidinyl ketone 4-allyl-3-amino selenourea (CU27) is chosen for further identification because it proves to be the most effective compound over others on CSC inhibition. Through ingenuity pathway analysis, it is shown CU27 may inhibit CSC through a well-known stemness-related transcription factor c-Myc. Gene set enrichment analysis, dual-luciferase reporter assays, expression levels of typical c-Myc targets, molecular docking, surface plasmon resonance, immunoprecipitation, and chromatin immunoprecipitation are conducted. These results together suggest CU27 binds c-Myc bHLH/LZ domains, inhibits c-Myc-Max complex formation, and prevents its occupancy on target gene promoters. In mouse models, CU27 significantly sensitizes sorafenib-resistant tumor to sorafenib, reduces the primary tumor size, and inhibits CSC generation, showing a dramatic anti-metastasis potential. Taken together, CU27 exerts inhibitory effects on CSC and CSC-associated traits in hepatocellular carcinoma (HCC) via c-Myc transcription activity inhibition. CU27 may be a promising therapeutic to treat sorafenib-resistant HCC.


Diuretic-induced hypokalemia in uncomplicated systemic hypertension: effect of plasma potassium correction on cardiac arrhythmias.
Sixteen patients with diuretic-induced hypokalemia underwent 24-hour ambulatory electrocardiographic monitoring during and after correction of hypokalemia. Plasma potassium averaged 2.83 +/- 0.08 mEq/liter before and 3.73 +/- 0.06 mEq/liter after correction with potassium chloride, triamterene or both. Premature atrial contractions decreased in 6 patients, increased in 6 and remained unchanged in 4. There was no improvement in ventricular ectopic activity after plasma potassium correction. Ventricular ectopic activity improved in 5 patients, worsened in 10 and remained unchanged in 1. Ventricular tachycardia was not observed in either phase. Plasma magnesium remained normal throughout. The investigators conclude that in patients with uncomplicated hypertension, correction of diuretic-induced hypokalemia does not significantly reduce the occurrence of spontaneous atrial or ventricular ectopic activity.


Urine Trinder spot test: a rapid salicylate screen for the emergency department.
To determine whether the urine Trinder spot test, performed by emergency physicians, is a sensitive bedside screen for salicylates. Prospective, blinded human protocol with subjects serving as their own controls. Urban Level I medical center. Ten male and two female volunteers with negative urine toxicologic screen results before the start of the study. Each participant ingested 975 mg of nonenteric coated aspirin. Serum and urine samples were collected before ingestion and 2 and 4 hours after ingestion. Three emergency physicians and a toxicology technician independently performed Trinder spot tests. Results were recorded as positive or negative for salicylate on the basis of color change (a purple reading was considered positive). All postingestion urine specimens were detected by all testers with 100% sensitivity. Two false positives occurred in the preingestion samples. Serum quantitative assays confirmed the presence of salicylates in all postingestion specimens. This pilot study suggests that emergency physicians can use the Trinder spot test as a sensitive bedside salicylate screen, potentially saving time and quantitative assay expense.


[Morphology of the tegument of Schistosoma intercalatum; comparison of three stocks from Cameroon, Zaire and Gabon].
The study of the teguments of male Schistosoma intercalatum with SEM shows two different morphological types: a) Type Cameroon (Edea) (consistent with the previous studies by Kuntz et al.). b) Type Zaïre (Kisangani) similar to type Gabon (Libreville).


Purine synthesis de novo in cultured lymphoblast cells derived from patients with gout.
Rates of de novo purine synthesis in lymphoblast cell cultures derived from ten patients with gout were compared with those from control individuals. Since the growth rate of the culture, an assay procedure was developed to account for the variation in lymphoblast growth rates and to permit valid quantitative comparison between purine synthesis in each cell line. Clear differences were demonstrated between the rates of purine synthesis in cells from normal control subjects and those from patients with a deficiency of hypoxanthine-guanine phosphoribosyltransferase activity (HPRT-deficient). Lymphoblasts from the gouty patients showed purine synthesis either within the normal range or intermediate between this and the HPRT-deficient cells. In patients having normal renal function, de novo purine synthesis of lymphoblast cells correlated with the degree of urate production as reflected by the urinary excretion of urate over a 24 h period. Three patients, with demonstrable excessive production of urate in vivo, exhibited increased purine synthesis in lymphoblasts. This increased synthesis did not appear to result from any of the enzyme mutations currently recognized as responsible for abnormal purine metabolism.


Extracellular vesicles secreted by Schistosoma mansoni contain protein vaccine candidates.
Herein we show for the first time that Schistosoma mansoni adult worms secrete exosome-like extracellular vesicles ranging from 50 to 130nm in size. Extracellular vesicles were collected from the excretory/secretory products of cultured adult flukes and purified by Optiprep density gradient, resulting in highly pure extracellular vesicle preparations as confirmed by transmission electron microscopy and Nanosight tracking analysis. Extracellular vesicle proteomic analysis showed numerous known vaccine candidates, potential virulence factors and molecules implicated in feeding. These findings provide new avenues for the exploration of host-schistosome interactions and offer a potential mechanism by which some vaccine antigens exert their protective efficacy.


Anaesthesia and Marfan's syndrome: case report.
An 18-year-old male with Marfan's syndrome underwent surgery for repair of an ascending aortic dissection. The clinical features of this congenital syndrome and the acute management of its complications are described. As elective surgery is frequently required for ocular, musculo-skeletal or cardiovascular problems in people with Marfan's syndrome, patients must be carefully assessed preoperatively for specific complications. Significant pulmonary problems include restriction of lung function due to pectus excavatum or kyphoscoliosis and intrinsic pulmonary involvement with emphysema, bronchogenic cysts and "honeycomb lung." This leads to a significant incidence of spontaneous pneumothorax and the danger of tension pneumothorax with positive pressure ventilation. The commonest causes of sudden death are cardiovascular complications, in particular rupture and dissection of the ascending aorta. Preoperative assessment should include echocardiography to determine the size of the aortic root. The anaesthetic technique chosen should both decrease myocardial contractility and avoid sudden increases in contractility, in order to minimise the risk of aortic dissection or rupture.


The diagnostic value of seminal adenosine triphosphate (ATP) in an in vitro fertilization (IVF) program.
The level of adenosine triphosphate (ATP) was quantitated in semen samples used for in vitro fertilization of human oocytes. Seminal ATP level correlated with the concentration and percentage motility of spermatozoa but not with the in vitro fertilization rate of human oocytes. Seminal ATP measurement appears to have little diagnostic value in predicting the fertilizing capacity of spermatozoa as evaluated by the multivariate stepwise discriminant analysis.


Arsenic, cadmium, mercury, sodium, and potassium concentrations in common foods and estimated daily intake of the population in Valdivia (Chile) using a total diet study.
This study was designed to estimate the dietary intake of total arsenic, inorganic arsenic, cadmium, mercury, sodium, and potassium by the general adult population (aged 18-65) of Valdivia, Chile. Calculations were based on a 24-h dietary recall survey. The highest dietary intake of t-As (73.0 μg/day), i-As (20.0 μg/day), Cd (18.0 μg/day), Hg (5.8 μg/day), Na+ (3112.8 mg/day), and K+ (2077.5 mg/day) were for 70-kg adults. Estimating carcinogenic risk (CR > 4 × 10-4) due to exposure to i-As indicated that consumers remain at low risk for cancer. The cumulative health risk was evaluated by summing the target hazard quotient of cadmium (0.26) mercury (0.27) and inorganic arsenic (0.96); this calculation allows us to express the total target hazard quotient as 1.50 where a value > 1 indicates that there is a potential health risk for the population. Total intake of Cd and Hg were therefore within the limits estimated as being safe whereas Na+ and K+ intake for the Valdivia population did not follow the recommended values established by the World Health Organization (WHO). The Na+ intake exceeded the daily recommended intake while K+ intake was lower than the daily recommended intake. This indicates a health risk for the Valdivia population.


Sexual selection and sperm diversity in primates.
Many aspects of primate sperm physiology and reproductive behavior have been influenced by sexual selection, especially in taxa exposed to sperm competition where females mate with multiple partners. Primate sperm diversity reflects therefore the evolutionary divergences of the different primate species and the impact of a combination of variables exerting selection pressures on sperm form, function, and competition. Thereby, mating systems, life cycle or ecological variables are some of the important factors driving sperm diversity and explaining variation in terms of sperm morphology, parameters or male sexual characters. Here, we address primate sperm diversity through a compilation of all data available in the literature concerning primate sperm parameters and relationships between them. We also review the factors that can influence primate sperm diversity (e.g. mating systems, trade-off between investments in precopulatory and postcopulatory sexual traits, male and female sexual behaviors, seasonality, social constraints, testosterone levels), and discuss also their relevance to our understanding of human reproduction.


Refraction of electromagnetic energy for wave packets incident on a negative-index medium is always negative.
We analyze refraction of electromagnetic wave packets on passing from an isotropic positive to an isotropic negative-refractive-index medium. We definitively show that in all cases the energy is always refracted negatively. For localized wave packets, the group refraction is also always negative.


Differential regulation of TNF-alpha and IL-1beta production from endotoxin stimulated human monocytes by phosphodiesterase inhibitors.
The effect of selective PDE-I (vinpocetine), PDE-III (milrinone, CI-930), PDE-IV (rolipram, nitroquazone), and PDE-V (zaprinast) isozyme inhibitors on TNF-alpha and IL-1beta production from LPS stimulated human monocytes was investigated. The PDE-IV inhibitors caused a concentration dependent inhibition of TNF-alpha production, but only partially inhibited IL-1beta at high concentrations. High concentrations of the PDE-III inhibitors weakly inhibited TNF-alpha, but had no effect on IL-1beta production. PDE-V inhibition was associated with an augmentation of cytokine secretion. Studies with combinations of PDE isozyme inhibitors indicated that PDE-III and PDE-V inhibitors modulate rolipram's suppression of TNF production in an additive manner. These data confirm that TNF-alpha and IL-1beta production from LPS stimulated human monocytes are differentially regulated, and suggest that PDE-IV inhibitors have the potential to suppress TNF levels in man.


Determination of dalcetrapib by liquid chromatography-tandem mass spectrometry.
The cholesteryl ester transfer protein modulator dalcetrapib is currently under development for the prevention of dyslipidemia and cardiovascular disease. Dalcetrapib, a thioester, is rapidly hydrolyzed in vivo to the corresponding thiophenol which in turn is further oxidized to the dimer and mixed disulfides (where the thiophenol binds to peptides, proteins and other endogenous thiols). These forms co-exist in an oxidation-reduction equilibrium via the thiol and cannot be stabilized without influencing the equilibrium, hence specific determination of individual components, i.e., in order to distinguish between the free thiol, the disulfide dimer and mixed disulfide adducts, was not pursued for routine analysis. The individual forms were quantified collectively as dalcetrapib-thiol (dal-thiol) after reduction under basic conditions with dithiothreitol to break disulfide bonds and derivatization with N-ethylmaleimide to stabilize the free thiol. The S-methyl and S-glucuronide metabolites were determined simultaneously with dal-thiol with no effect from the derivatization procedure. Column-switching liquid chromatography-tandem mass spectrometry provided a simple, fast and robust method for analysis of human and animal plasma and human urine samples. Addition of the surfactant Tween 80 to urine prevented adsorptive compound loss. The lower limits of quantitation (LLOQ) were 5 ng/mL for dal-thiol, and 5 ng/mL for the S-methyl and 50 ng/mL for the S-glucuronide metabolites. Using stable isotope-labeled internal standards, inter- and intra-assay precisions were each <15% (<20% at LLOQ) and accuracy was between 85 and 115%. Recovery was close to 100%, and no significant matrix effect was observed.


Pacritinib is a potent ACVR1 inhibitor with significant anemia benefit in patients with myelofibrosis.
In patients with cytopenic myelofibrosis, treatment with the JAK2/IRAK1 inhibitor pacritinib was associated with anemia benefit in the phase 3 PERSIST-2 study. The impact of pacritinib on transfusion independence (TI) has not been previously described, nor has the mechanism by which pacritinib improves anemia been elucidated. Because it has been previously postulated that inhibition of activin A receptor, type 1 (ACVR1)/activin receptor-like kinase-2 improves anemia in patients with myelofibrosis via suppression of hepcidin production, we assessed the relative inhibitory potency of pacritinib compared with other JAK2 inhibitors against ACVR1. Pacritinib inhibited ACVR1 with greater potency (half-maximal inhibitory concentration [IC50] = 16.7 nM; Cmax:IC50 = 12.7) than momelotinib (IC50 = 52.5 nM; Cmax:IC50 = 3.2), fedratinib (IC50 = 273 nM; Cmax:IC50 = 1.0), or ruxolitinib (IC50 > 1000; Cmax:IC50 < 0.01). Pacritinib's inhibitory activity against ACVR1 was corroborated via inhibition of downstream SMAD signaling in conjunction with marked suppression of hepcidin production. Among patients on PERSIST-2 who were not transfusion independent at baseline based on Gale criteria, a significantly greater proportion achieved TI on pacritinib compared with those treated on best available therapy (37% vs 7%, P = .001), and significantly more had a ≥50% reduction in transfusion burden (49% vs 9%, P < .0001). These data indicate that the anemia benefit of the JAK2/IRAK1 inhibitor pacritinib may be a function of potent ACVR1 inhibition.


Assessment of thermal and temporal stability of SARS-CoV-2 samples using real-time qRT-PCR.
As per the guidelines of the Indian Council of Medical Research, nasopharyngeal and oropharyngeal swabs in viral transport medium (VTM) are to be stored at 4 °C for less than 5 days and for more than 5 days at -70 °C. Samples are not transported or stored as per prescribed conditions because of the limitations, resulting in an apprehensive diagnosis. The aim of the study was to test the stability of the SARS-CoV-2 sample stored in VTM at different temperatures. In this study, the stability of 21 positive and 9 negative samples for SARS-CoV-2 was evaluated in commercial VTM at different temperatures (-80 °C, -20 °C, 4 °C, and 25 to 30 °C). Stability was checked for up to 50 days in the above storage conditions at different intervals. PathoDetect™ and Hi-PCR® kits were used for the detection of the four genes of SARS-CoV-2. The Cycle Threshold (Ct) value for determining the positivity of samples for PathoDetect™ was < 40 and for Hi-PCR® was < 38. The SARS-CoV-2 confirmatory genes (RdRp and E genes) and the internal housekeeping gene remained detectable even on the 50th day of the study. The Ct of the RdRp and E genes were found to increase with storage duration, but all positive samples remained positive till the end of the study, or the Ct value remained below the cut-off level. The negative samples gave consistent results until the end of the study. When the differences in Ct values were compared between the days in a set of experiments, they were not significantly different except in a few samples. The SARS-CoV-2 genetic materials in commercial VTM were stable at room temperature to -80 °C for 50 days.


MR Virtual Biopsy of Solid Renal Masses: An Algorithmic Approach.
Between 1983 and 2002, the incidence of solid renal tumors increased from 7.1 to 10.8 cases per 100,000. This is in large part due to the increase in the volume of ultrasound and cross-sectional imaging, although a majority of solid renal tumors are still found incidentally. Ultrasound and computed tomography (CT) have been the mainstay of renal mass screening and diagnosis but recent advances in magnetic resonance (MR) technology have made this the optimal choice when diagnosing and staging renal tumors. Our purpose in writing this review is to survey the modern MR imaging approach to benign and malignant solid renal tumors, consolidate the various imaging findings into an easy-to-read reference, and provide an imaging-based, algorithmic approach to renal mass characterization for clinicians. MR is at the forefront of renal mass characterization, surpassing ultrasound and CT in its ability to describe multiple tissue parameters and predict tumor biology. Cutting-edge MR protocols and the integration of diagnostic algorithms can improve patient outcomes, allowing the imager to narrow the differential and better guide oncologic and surgical management.


Exposure to different sources of second-hand smoke during pregnancy and its effect on urinary cotinine and tobacco-specific nitrosamine (NNAL) concentrations.
To date, no research exists on the role that different sources of exposure to second-hand smoke (SHS) have on 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) and nicotine uptake, assessed via urinary 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL) and cotinine concentrations of non-smoking pregnant women, nor the differences in NNAL concentrations among pregnant women who quit smoking in comparison to those who do not. As part of the 'Rhea' mother childbirth cohort in Crete, Greece, 1317 mother-child pairs were followed-up until delivery, while among a subsample, maternal urine was assessed for its NNAL (n=117) and cotinine concentrations (n=377). Pregnant women who continued to smoke during pregnancy were found to have geometric mean urinary NNAL concentrations of 0.612 pmol/ml, in comparison to the 0.100 pmol/ml of ex-smokers and 0.0795 pmol/ml of non-smokers exposed to SHS. Exposure to SHS in the home was associated with a 4.40 ng/ml increase in urinary cotinine levels, while reported exposure to SHS in cars was associated with an even higher (8.73 ng/ml) increase in cotinine concentrations and was strongly related to NNAL concentrations. Exposure to SHS in the workplace and in public places was also shown to increase cotinine and NNAL concentrations. The NNAL:cotinine ratio was found to be higher among pregnant women who were exposed to SHS but did not smoke (p<0.001). Using cotinine levels as an indicator of NNK, exposure due to SHS during pregnancy leads to an underestimation of exposure to NNK uptake. Moreover, each source of exposure contributed to the increase in cotinine levels, indicating the importance of avoiding SHS exposure from any source.


Characterization of MHC ancestral haplotypes associated with insulin-dependent diabetes mellitus: evidence for involvement of non-HLA genes.
Insulin-dependent diabetes mellitus (IDDM) is associated with several DR3- or DR4-containing ancestral haplotypes (AHs). Using pulsed field gel electrophoresis (PFGE), long range maps of 35 haplotypes have been derived and classified. Two diabetogenic DR3-containing AHs (8.1 and 18.2) possess deletions in the central non-HLA region; these have not been found on non-diabetogenic AHs tested to date. In addition, 8.1 and 18.2 also carry other deletions not found on other AHs. Three DR4 containing AH lack a Not I site, which may imply excision of an unidentified gene. These and other data suggest that deletions may be relevant to the pathogenesis of autoimmune disease, possibly through causing quantitative differences in autoimmune responses involved in IDDM. The MHC contains several regions of potential interest in relation to susceptibility to IDDM; these may explain the association with only certain DR3- and DR4-carrying AH and DR3,4 heterozygosity in terms of cis and trans interactions. On the other hand, the class II region may be particularly important in protection.


Continuous arteriovenous hemodiafiltration in postoperative and traumatic renal failure.
Management of acute renal failure (ARF) in surgical patients has relied on supportive measures including hemodialysis and peritoneal dialysis. An alternative technique currently available is continuous arteriovenous hemodiafiltration (CAVH-D). Records of 44 surgical patients with ARF who were treated with CAVH-D in our surgical intensive care unit from 1989 to 1992 were reviewed. Thirty-five patients underwent emergency operations, and 4 patients underwent elective operations. Thirty-three patients were hemodynamically unstable immediately prior to the institution of CAVH-D, making hemodialysis a contraindication. A total of 565 CAVH-D days with an average of 13 days per patient were evaluated. Seventeen patients survived, with recovery of renal function in 13 patients. Vascular access was obtained via 227 percutaneous femoral catheters and 4 Scribner shunts. Seven vascular complications occurred, including arteriovenous fistula, pseudoaneurysm, limb ischemia, femoral artery hemorrhage, and femoral vein thrombosis. Based on these data, we conclude that CAVH-D is a safe and effective alternative in surgical patients with ARF.


Development of Schizochytrium sp. strain HS01 with high-DHA and low-saturated fatty acids production by multi-pronged adaptive evolution.
Docosahexaenoic acid (DHA) is an important omega-3 unsaturated fatty acid and has been widely applied in medicine, food additives, and feed ingredients. The fermentative production of DHA using microorganisms, including Schizochytrium sp., attracted much attention due to its high production efficiency and environment friendly properties. An efficient laboratory evolution approach was used to improve the strain's performance in this study. A multi-pronged laboratory evolution approach was applied to evolve high-yield DHA-producing Schizochytrium strain. We further employed comparative transcriptional analysis to identify transcriptional changes between the screened strain HS01 and its parent strain GS00. After multiple generations of ALE, a strain HS01 with higher DHA content and lower saturated fatty acids content was obtained. Low nitrogen conditions were important for enhancing DHA biosynthesis in HS01. The comparative transcriptional analysis results indicated that during the fermentation process of HS01, the expression of key enzymes in the glycolysis, the pentose phosphate pathway and the tricarboxylic acid cycle were up-regulated, while the expression of polyketide synthase genes and fatty acid synthesis genes were similar to those in GS00. The results suggest that the improved DHA production capacity of HS01 is not due to enhancement of the DHA biosynthesis pathway, but rather related to modulation of central metabolism pathways.


Handgrip strength is associated with risks of new-onset stroke and heart disease: results from 3 prospective cohorts.
Stroke and heart disease are two major contributors to the global disease burden. We aimed to evaluate and compare the roles of different handgrip strength (HGS) expressions in predicting stroke and heart disease in three nationally representative cohorts. This longitudinal study used data from the Health and Retirement Study (HRS), the Survey of Health, Ageing, and Retirement in Europe (SHARE), and the China Health and Retirement Longitudinal Study (CHARLS). The Cox proportional hazard model was applied to analyze the relationship between HGS and stroke and heart disease, and Harrell's C index was used to assess the predictive abilities of different HGS expressions. A total of 4,407 participants suffered from stroke and 9,509 from heart disease during follow-up. Compared with the highest quartile, participants in the lowest quartile of dominant HGS, absolute HGS and relative HGS possessed a significantly higher risk of new-onset stroke in Europe, America, and China (all P < 0.05). After adding HGS to office-based risk factors, there were minimal or no differences in the increases of Harrell's C indexes among three HGS expressions. In contrast, the modest association between HGS and heart disease was only seen in SHARE and HRS, but not in CHARLS. Our findings support that HGS can be used as an independent predictor of stroke in middle-aged and older European, American and Chinese populations, and the predictive ability of HGS may not depend on how it is expressed. The relationship between HGS and heart disease calls for further validation.


Small bowel polyps and tumours: endoscopic detection and treatment by double-balloon enteroscopy.
Double-balloon enteroscopy has allowed us not only to inspect deeply the small bowel but also to carry out interventions for diseases of the small bowel. To evaluate the utility of double-balloon enteroscopy for the diagnosis and therapy of these lesions. All patients undergoing double-balloon enteroscopy for evaluation of small bowel polyps and tumours during a 3.75-year period at a university referral hospital were studied. The types of polyps and tumours as well as endoscopic technique of removal, surgery and complications were documented. The incidence of small bowel polyps and tumours in-patients undergoing DBE was 9.6%. A total of 40 double-balloon enteroscopy procedures were performed in 29 patients [13 female (44.8%), mean age 51 years, range 22-74]. The following lesions were found most frequently: adenomas in familial adenomatous polyposis syndrome, n = 8; hamartomas, n = 4 (Peutz-Jeghers and Cronkhite Canada syndromes), jejunal adenocarcinoma n = 5, neuroendocrine tumour n = 4 and others n = 6. The incidence of small bowel tumours in those in-patients who were undergoing double-balloon enteroscopy was 10%. Double-balloon enteroscopy is useful for the diagnosis and treatment of small bowel polyps and tumours.


[Various characteristics of the synthesis of nucleic acids and proteins in the prostate of castrated rabbits after separate and successive administration of testosterone and 5 alpha-dihydrotestosterone].
The results are presented of studying nucleic acid and protein synthesis in the rabbit prostate. It was shown that incorporation of radioactive precursors into the prostate DNA, RNA and proteins is diminished two months after gonadectomy of the animals. Testosterone and its metabolite 5 alpha-dihydrotestosterone markedly intensify RNA and protein synthesis in the prostate of castrated rabbits, whereas 5 alpha-dihydrotestosterone only exerts a stimulating effect upon DNA synthesis. Preliminary testosterone propionate injections to gonadectomized rabbits delay DNA synthesis, induced by 5 alpha-dihydrotestosterone, and decrease the marker incorporation into RNA and protein, comparatively to the effect of each separate androgen.


Nephrotoxic activity in rats fed diets containing DL-3-(N-phenylethylamino)-alanine.
Rats were fed DL-3-(N-phenylethalamino)-alanine which resulted in kidney lesions histologically identical with those produced by the structurally related compound lysinoalanine. Possible mechanisms for nephrotoxicity are discussed.


Inequalities in body mass index, diet and physical activity in the UK: Longitudinal evidence across childhood and adolescence.
We use longitudinal data across a key developmental period, spanning much of childhood and adolescence (age 5 to 17, years 2006-2018) from the UK Millennium Cohort Study, a nationally representative study with an initial sample of just over 19,000. We first examine the extent to which inequalities in overweight, obesity, BMI and body fat over this period are consistent with the evolution of inequalities in health behaviours, including exercise and healthy diet markers (i.e., skipping breakfast) (n = 7,220). We next study the links between SES, health behaviours and adiposity (BMI, body fat), using rich models that account for the influence of a range of unobserved factors that are fixed over time. In this way, we improve on existing estimates measuring the relationship between SES and health behaviours on the one hand and adiposity on the other. The advantage of the individual fixed effects models is that they exploit within-individual changes over time to help mitigate biases due to unobserved fixed characteristics (n = 6,883). We observe stark income inequalities in BMI and body fat in childhood (age 5), which have further widened by age 17. Inequalities in obesity, physical activity, and skipping breakfast are observed to widen from age 7 onwards. Ordinary Least Square estimates reveal the previously documented SES gradient in adiposity, which is reduced slightly once health behaviours including breakfast consumption and physical activity are accounted for. The main substantive change in estimates comes from the fixed effects specification. Here we observe mixed findings on the SES associations, with a positive association between income and adiposity and a negative association with wealth. The role of health behaviours is attenuated but they remain important, particularly for body fat.


Disinfection effect of dental impression tray adhesives.
Iatrogenic infections are serious problems in dental offices. Impression tray adhesives are delivered in glass containers with a fixed brush attached inside the cap. Using the brush for application of the impression tray adhesive on a contaminated impression tray or prostheses, pathogen transmission by replacing the cap with the brush is possible. Bacterial strains (patient strains and in vitro strains) were supervaccinated on Columbia agar. The bacterial solution was diluted with TSB and aerobically grown, and starting concentration was 1 × 10(7) cfu/ml. The stock solution was placed on Columbia agar. Alginate, polyether, and silicon impression tray adhesives were applied to the center of the particular blood agar plates and incubated for 48 h. The expansion of the inhibition zone assays were measured using a microscope. Twenty-one different bacterial strains were selected in the saliva samples of 20 patients. The growth inhibition for alginate impression tray adhesive was 1.1 % (±0.3) of the patient strains. The overgrowth of polyether impression tray adhesive was 30.6 % (±9.3) and for silicon impression tray adhesive 11.8 % (±5.0). In in vitro strains, alginate impression tray adhesive performed an inhibition of 0.7 % (±0.3). The overgrowth of polyether impression tray adhesive was 7.0 % (±1.6) and for silicon impression tray adhesive was 6.5 % (±1.3). Using the fixed brush for application of the impression tray adhesive on multiple patients, a cross-contamination cannot be ruled out. An application of the impression tray adhesive with a pipette and a single-use brush would eliminate the contamination.


Long-term variable photoperiod exposure impairs the mPFC and induces anxiety and depression-like behavior in male wistar rats.
Long-term shift work can cause circadian misalignment, which has been linked to anxiety and depression. However, the associated pathophysiologic changes have not been described in detail, and the mechanism underlying this association is not fully understood. To address these points, we used a rat model of CM induced by long-term variable photoperiod exposure [L-VP] (ie, for 90 days). We compared the numbers of neurons, astrocytes, and dendritic spines; dendrite morphology; long-term potentiation (LTP), long-term depression (LTD) and paired-pulse ratio (PPR); expression of glutamate receptor [N-methyl-d-aspartate receptor (NMDAR) and α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR)] subunits and brain-derived neurotrophic factor (BDNF) in the medial prefrontal cortex (mPFC); and the anxiety and depression behaviors between rats in the circadian misalignment (CM) and circadian alignment (CA, with normal circadian rhythm) groups. The results showed that L-VP reduced the number of neurons and astrocytes in the mPFC and decreased the number of dendritic spines, dendrite complexity, LTP, LTD, PPR, and expression of glutamate receptors (GluR1, GluR2, GluR3, NMDAR2A, and NMDAR2B) and BDNF in the mPFC. L-VP also induced anxiety and depression-like behaviors, as measured by the open field test, elevated plus-maze, sucrose preference test, and forced swim test. These results suggest that CM induces a loss of neurons and astrocytes and synaptic damage in surviving pyramidal cells in the mPFC might be involved in the pathophysiology of anxiety and depression.


Nephron organoids derived from human pluripotent stem cells model kidney development and injury.
Kidney cells and tissues derived from human pluripotent stem cells (hPSCs) may enable organ regeneration, disease modeling and drug screening. We report an efficient, chemically defined protocol for differentiating hPSCs into multipotent nephron progenitor cells (NPCs) that can form nephron-like structures. By recapitulating metanephric kidney development in vitro, we generate SIX2+ SALL1+ WT1+ PAX2+ NPCs with 90% efficiency within 9 days of differentiation. The NPCs possess the developmental potential of their in vivo counterparts and form PAX8+ LHX1+ renal vesicles that self-organize into nephron structures. In both two- and three-dimensional culture, NPCs form kidney organoids containing epithelial nephron-like structures expressing markers of podocytes, proximal tubules, loops of Henle and distal tubules in an organized, continuous arrangement that resembles the nephron in vivo. We also show that this organoid culture system can be used to study mechanisms of human kidney development and toxicity.


[Alopecia areata universalis under treatment with sitagliptin : Possible immunological effect of dipeptidyl peptidase-4 inhibitors?]
A 64-year old man developed alopecia universalis after one month of treatment with metformin and sitagliptin, a dipeptidyl peptidase‑4 (DPP-4) inhibitor. Diabetes treatment was changed to another genericum of sitagliptin and dapagliflozin. Following our recommendation, sitagliptin was interrupted and monotherapy with dapagliflozin was continued. After 6 weeks, sitagliptin was reassumed due to unsatisfactory diabetes control. Alopecia did not improve. We suspect a connection between DPP‑4 inhibition and development of alopecia due to its immunological potential. We assume that the treatment interruption might have been too short to induce regrowth of hair. DPP‑4 may result in both inhibition and activation of the immune system.


Adverse effects of monobactams and carbapenems.
Monobactams and carbapenems are 2 classes of beta-lactam antibiotics that were introduced in the 1980s. This review considers the monobactam aztreonam and the carbapenems imipenem and meropenem. Imipenem is administered together with cilastatin, which inhibits the enzymatic breakdown of imipenem in the kidney. The antibacterial activities of these drugs are quite different from older beta-lactams. Aztreonam is directed towards aerobic Gram-negative bacteria, especially Pseudomonas aeruginosa, while imipenem and meropenem are active against both aerobic and anaerobic Gram-positive and Gram-negative bacteria. Thus, these drugs should be reserved for patients who have a special need for them. They are also structurally different from older beta-lactams and possess different adverse drug reaction profiles. It was initially suggested that aztreonam would be less immunogenic than previous beta-lactams because reactive breakdown products acting as haptens are less likely to be formed. Clinical reports now support this assumption, and, in particular, cross hypersensitivity between aztreonam and other beta-lactams seems to be rare which makes the drug a useful therapeutic alternative. However, hypersensitivity to aztreonam does occur. The predominant concern in terms of adverse reactions to imipenem/cilastatin is the increased tendency to cause seizures compared with other beta-lactams. The risk of producing a seizure is highly associated with inadequate dose adjustment in relation to kidney function. If appropriate care is taken, seizures occur in less than 1% of patients treated. However, it is possible that concomitant administration of other drugs with neurotoxic profiles (e.g. theophylline and cyclosporin) given in overdose, may increase the risk of seizures.(ABSTRACT TRUNCATED AT 250 WORDS)


Characterization of mtDNA variation in a cohort of South African paediatric patients with mitochondrial disease.
Mitochondrial disease can be attributed to both mitochondrial and nuclear gene mutations. It has a heterogeneous clinical and biochemical profile, which is compounded by the diversity of the genetic background. Disease-based epidemiological information has expanded significantly in recent decades, but little information is known that clarifies the aetiology in African patients. The aim of this study was to investigate mitochondrial DNA variation and pathogenic mutations in the muscle of diagnosed paediatric patients from South Africa. A cohort of 71 South African paediatric patients was included and a high-throughput nucleotide sequencing approach was used to sequence full-length muscle mtDNA. The average coverage of the mtDNA genome was 81±26 per position. After assigning haplogroups, it was determined that although the nature of non-haplogroup-defining variants was similar in African and non-African haplogroup patients, the number of substitutions were significantly higher in African patients. We describe previously reported disease-associated and novel variants in this cohort. We observed a general lack of commonly reported syndrome-associated mutations, which supports clinical observations and confirms general observations in African patients when using single mutation screening strategies based on (predominantly non-African) mtDNA disease-based information. It is finally concluded that this first extensive report on muscle mtDNA sequences in African paediatric patients highlights the need for a full-length mtDNA sequencing strategy, which applies to all populations where specific mutations is not present. This, in addition to nuclear DNA gene mutation and pathogenicity evaluations, will be required to better unravel the aetiology of these disorders in African patients.


'Patients with lung conditions should have specialist support'.
Patients with lung disease must have a nurse specialist to support them, the British Lung Foundation says.


Synthesis of a CdSe-graphene hybrid composed of CdSe quantum dot arrays directly grown on CVD-graphene and its ultrafast carrier dynamics.
We report the original fabrication and performance of a photocurrent device that uses directly grown CdSe quantum dots (QDs) on a graphene basal plane. The direct junction between the QDs and graphene and the high quality of the graphene grown by chemical vapor deposition enables highly efficient electron transfer from the QDs to the graphene. Therefore, the hybrids show large photocurrent effects with a fast response time and shortened photoluminescence (PL) lifetime. The PL lifetime quenching can be explained as being due to the efficient electron transfer as evidenced by femtosecond transient absorption spectroscopy. These hybrids are expected to find applications in flexible electronics and optoelectronic devices.


Correlation of the L-Arginine Pathway with Thrombo-Inflammation May Contribute to the Outcome of Acute Ischemic Stroke.
Immune responses contribute to secondary injury after acute ischemic stroke (AIS), and metabolites of the L-arginine pathway are associated with stroke outcome. Here, we analyzed the relationship of the L-arginine pathway with thrombo-inflammatory biomarkers in AIS and their additive and independent associations to outcome. Serial changes in P-selectin, tPA, MCP-1, sCD40L, IL-6, IL-8, L-arginine, and asymmetric and symmetric dimethylarginine (ADMA, SDMA) were investigated in 55 patients with AIS and without infection within 6 and 72 hours after stroke onset. Outcomes were assessed as National Institutes of Health Stroke Scale (NIHSS) worsening by 24 hours, poststroke infection, and death by 1 month. Serum levels of L-arginine showed negative correlation, whereas ADMA and SDMA showed positive correlation with thrombo-inflammatory biomarkers in the hyperacute phase. Most of these correlations disappeared by 72 poststroke hours. Correlation of MCP-1 with both ADMA and SDMA levels at 6 hours was associated with both NIHSS worsening and poststroke infections, respectively; sCD40L and SDMA correlation at 6 hours was also associated with NIHSS worsening. Negative correlation between P-selectin and L-arginine concentrations in the hyperacute phase was associated with NIHSS worsening. Strong negative correlation was found between IL-6 and L-arginine levels in the hyperacute phase in patients with poststroke infection. Only L-arginine and SDMA at 72 hours were independently associated with poststroke infection respectively. Concentration of L-arginine and ADMA/SDMA differentially correlates with thrombo-inflammation in the hyperacute phase of ischemic stroke. Such correlations are independently associated with poststroke infection but not with other outcomes.


Investigating the effect of systematically modifying the molar ratio of hydrogen bond donor and acceptor on solvation characteristics of deep eutectic solvents formed using choline chloride salt and polyalcohols.
Choline chloride-based deep eutectic solvents (DESs) are immensely popular in organic synthesis, catalysis, electrochemistry, and separation science. A popular choice of hydrogen bond donor (HBD) among these DESs consists of both straight-chain and branched polyols that can incorporate additional functional groups, such as ether linkages. Previous studies have shown that the extraction efficiency is significantly altered when the molar ratio of HBD in choline chloride-based DES systems is varied, but no study has been able to relate it to their solvation characteristics. This is largely due to the limited sensitivity of existing solvatochromic dye techniques to detect minor changes in solvation interactions when the DES composition is varied. In this study, inverse gas chromatography was employed for the first time to investigate the variation in solvation properties for DESs comprised of choline salts as hydrogen bond acceptors (HBAs) and polyols as HBDs when their HBA/HBD ratio is systematically altered. Unlike many organic solvents, DES systems investigated in this work possessed a significant hydrogen bond character. It was observed that the hydrogen bond basicity generally plateaued at higher molar ratios of HBD while the hydrogen bond acidity was observed to be the highest at HBA/HBD ratios of 1:10 in all DESs. Amongst all solvents, neat HBDs (triethylene glycol and 1,8-octane diol) possessed the weakest hydrogen bond basicity since they lack the chloride anion that acts as the primary hydrogen bond acceptor. Results from this study demonstrate that the solvation characteristics of DESs are largely different from their starting materials while the HBA/HBD ratio further influences their solvation interactions that can in turn impact important parameters such as extraction yields.


Measuring attitudes toward participation in cancer treatment and cancer prevention trials: the Attitudes Toward Cancer Trials Scales (ACTS).
This investigation aimed to develop psychometric instruments that measure attitudes toward participating in cancer treatment trials (CTs) and cancer prevention trials (CPTs), that is, the Attitudes Toward Cancer Trials Scales (ACTS). A conceptualized construct of attitudes toward CTs and CPTs guided the writing of items for psychometric measurement. An expert panel assessment condensed reduced items to 116, and these were formatted into a self-report written survey. Data collection occurred within multiple settings, targeting an ethnically diverse sample (N = 312). Item and principal component analyses empirically supported the Attitudes Toward Cancer Trials Scales (ACTS), a 2-dimensional instrument containing an 18-item CT scale (four components) and a 16-item CPT scale (3 components) with Cronbach's alpha values of .86 and .89, respectively. Four components comprised the CT scale: personal benefits, personal barriers and safety, personal and social value, and trust in the research process. Three components comprised the CPT scale: personal barriers and safety, altruism, and personal value. Early evidence of the internal consistency reliability and construct validity of the ACTS was provided by the sample.


Genetics of obsessive-compulsive disorders: new findings and challenges.
A review of the current state of research in the genetics of obsessive-compulsive disorder (OCD) is presented. OCD is a neuropsychiatric condition that affects 1-2% of the population and often has an early age at onset of symptoms. OCD has been shown to be familial, and a major gene effect has been reported. However, phenotypic and genetic heterogeneity of OCD poses multiple challenges for locating susceptibility genes. Strategies such as the use of phenotypic subtyping (using tic disorders or other anxiety disorders) and endophenotyping based on brain mechanisms underlying OCD (functional brain imaging and neuropsychological measures) may open ways to understand the genetic components of OCD. Using child probands and extended families for linkage an association studies is another venue to obtain greater informative families for genetic studies. A better understanding of environmental triggers, OCD subtypes and OCD pathophysiology will lead to locating genes that confer risk to OCD.


Successful primary angioplasty in Hughes syndrome.
Acute myocardial infarction is a well-recognized complication of the Hughes syndrome but its optimal treatment is uncertain. We report a case of a 42-year-old man with a history of previous arterial and venous thrombosis who presented with an acute myocardial infarction that was successfully treated by primary angioplasty and stenting.


Randomized Controlled Trial of Balloon Dilation in Treatment of Subglottic Stenosis With a Rabbit Model.
Identify the effects of balloon dilation duration and topical ciprofloxacin-dexamethasone application in treatment of subglottic stenosis. Randomized controlled trial. Animal research facility. Forty-four rabbits underwent subglottic injury in an Institutional Animal Care and Use Committee-approved study. One week after injury, the subglottis of each rabbit was measured and treated with endoscopic balloon dilation for 2 rounds of short duration (SBD; 3 seconds), long duration (LBD; 30 seconds), or LBD with topical ciprofloxacin-dexamethasone application (LBD+C). The subglottis of each rabbit was remeasured at the study endpoint: 1 month postdilation or following development of life-threatening respiratory distress. Of 44 rabbits, 35 (80%) survived to endoscopic balloon dilation, with 21 rabbits developing a grade III Cotton-Myer stenosis. Prior to dilation, there was no difference in stenosis rates among groups (all subjects, P = .99; grade III stenosis only, P = .52). Among grade III subjects, improvement in stenosis after dilation was -1% (SD, 21%) for SBD, 27% (SD, 38%) for LBD, and 58% (SD, 29%) for LBD+C (P = .01). Early euthanasia/death rates among grade III subjects were 85% for SBD, 63% for LBD, and 17% for LBD+C (P = .03). Time to early euthanasia/death was 5.0 days for the SBD group and 8.4 days for the LBD group (P = .04). SBD was inferior to LBD or LBD+C in multiple metrics. LBD+C offered significant improvements in stenosis size and mortality over the SBD group and had the lowest rate of early mortality. Further research is needed to identify optimal balloon dilation treatment duration.


Decolorization of Reactive Red 2 by advanced oxidation processes: Comparative studies of homogeneous and heterogeneous systems.
This study investigated the decolorization of the Reactive Red 2 in water using advanced oxidation processes (AOPs): UV/TiO2, UV/SnO2, UV/TiO2+SnO2, O3, O3+MnO2, UV/O3 and UV/O3+TiO2+SnO2. Kinetic analyses indicated that the decolorization rates of Reactive Red 2 could be approximated as pseudo-first-order kinetics for both homogeneous and heterogeneous systems. The decolorization rate at pH 7 exceeded pH 4 and 10 in UV/TiO2 and UV/TiO2+SnO2 systems, respectively. However, the rate constants in the systems (including O3) demonstrated the order of pH 10>pH 7>pH 4. The UV/TiO2+SnO2 and O3+MnO2 systems exhibited a greater decolorization rate than the UV/TiO2 and O3 systems, respectively. Additionally, the promotion of rate depended on pH. The variation of dye concentration influenced the decolorization efficiency of heterogeneous systems more significant than homogeneous systems. Experimental results verified that decolorization and desulfuration occurred at nearly the same rate. Moreover, the decolorization rate constants at pH 7 in various systems followed the order of UV/O3 > or = O3+MnO2 > or = UV/O3+TiO2+SnO2 > O3 > UV/TiO2+SnO2 > or = UV/TiO2 > UV/SnO2.


Mechanism of respiration-driven proton translocation in the inner mitochondrial membrane. Analysis of proton translocation associated with oxidation of endogenous ubiquinol.
A study is presented of the kinetics and stoichiometry of fast proton translocation associated to aerobic oxidation of components of the mitochondrial respiratory chain. 1. Aerobic oxidation of ubiquinol and b cytochromes is accompanied in EDTA particles, obtained by sonication of beef-heart mitochondria, by synchronous proton uptake. 2. The rapid proton uptake associated to oxidation and b cytochromes is greatly stimulated by valinomycin plus K+, but is unaffected by carbonyl cyanide p-trifluoromethoxyphenylhydrazone. 3. 4 gion H+ are taken up per mol ubiquinol oxidized by oxygen. This H+/2e- ratio, measured in the rapid anaerobic-aerobic transition of the particles is unaffected by carbonyl cyanide p-trifluoromethoxyphenylhydrazone. 4. Intact mitochondria aerobic oxidation of oxygen-terminal electron carriers is accompanied by antimycin-insensitive synchronous proton release, oxidation of ubiquinol and reduction of b cytochromes. The amount of protons released is in excess with respect to the amount of ubiquinol oxidized. 5. It is concluded that electron flow along complex III, from ubiquinol to cytochrome c, is directly coupled to vectorial proton translocation. The present data suggest that there exist(s) between ubiquinol and cytochrome c one (or two) respiratory carrier(s), whose oxido-reduction is directly linked to effective transmembrane proton translocation.


Integument structure and function in juvenile Xenopus laevis with disrupted thyroid balance.
The skin is the largest organ in the body and is a barrier between the internal and external environment. The present study evaluates how PTU, a goitrogen, that is used to treat hyperthyroidism affects the structure and electrical properties of the frog (Xenopus laevis) skin. The results are considered in the context of the two-membrane model established in the seminal work of Ussing and collegues in the 1940s and 1950s. In vitro experiments with skin from Xenopus adults revealed that PTU can act directly on skin and causes a significant increase (p<0.05, One-way ANOVA) in short circuit current (Isc) via an amiloride-insensitive mechanism. Juvenile Xenopus exposed to waterborne PTU (5 mg/L) had a significantly bigger and more active thyroid gland (p<0.01, Student's t-test) than control Xenopus. The bioelectric properties of skin taken from Xenopus juveniles treated with PTU in vivo had a lower Isc, (3.05±0.4, n=13) and Rt (288.2±39.5) than skin from control Xenopus (Isc, 4.19±1.14, n=14; Rt, 343.3±43.3). A histological assessment of skin from PTU treated Xenopus juveniles revealed the epidermis was significantly thicker (p<0.01, Student's t-test) and had a greater number of modified exocrine glands (p<0.01, Student's t-test) in the dermis compared to control skin. Modifications in skin structure are presumably the basis for its changed bioelectric properties and the study highlights a site of action for environmental chemicals which has been largely neglected.


Effects of thiocyanate on cytosol androgen receptor from Shionogi carcinoma 115.
The effects of KSCN and other chaotropic salts on the androgen receptor in cytosol of Shionogi carcinoma 115 were studied by means of charcoal adsorption assay and sucrose gradient centrifugation. When KSCN or NaSCN was added to the [3H]-dihydrotestosterone-cytosol mixture at the final concentration of 0.5 M, the androgen binding to the cytosol receptor was considerably inhibited. The inhibition reached maximum within 5 h at 0 degrees C and was dependent on the kind of chaotropic anion added: the potency of inhibitory effect in descending order was KSCN greater than KI greater than KBr greater than KCl. The inhibition was not observed in the estradiol-receptor interaction with KSCN or NaSCN up to 0.5 M. When 0.5 M KSCN-treated androgen-cytosol mixture was subjected to gel filtration or (NH4)2SO4 fractionation to remove the salt, a partial recovery (30-40%) in specific binding activity was observed. The binding activity of androgen receptor was unaffected by a treatment with KSCN up to 0.1 M and the androgen-receptor complex sedimented in a 5S form in 0.1-0.3 M KSCN, 0.5 M KCl or 0.5 M KBr. These results suggest that the binding activity of androgen receptor is more susceptible than that of estrogen receptor to chaotropic salts which cause impairment in intramolecular hydrophobic interactions.


Bayesian filtering for model predictive control of stochastic gene expression in single cells.
This study describes a method for controlling the production of protein in individual cells using stochastic models of gene expression. By combining modern microscopy platforms with optogenetic gene expression, experimentalists are able to accurately apply light to individual cells, which can induce protein production. Here we use a finite state projection based stochastic model of gene expression, along with Bayesian state estimation to control protein copy numbers within individual cells. We compare this method to previous methods that use population based approaches. We also demonstrate the ability of this control strategy to ameliorate discrepancies between the predictions of a deterministic model and stochastic switching system.


No evidence for global decrease in CO2 concentration during the first wave of COVID-19 pandemic.
Numerous studies have reported that CO2 emissions have decreased because of global lockdown during the first wave of the COVID-19 pandemic. However, previous estimates of the global CO2 concentration before and after the outbreak of the COVID-19 pandemic are limited because they are based on energy consumption statistics or local specific in-situ observations. The aim of the study was to explore objective evidence for various previous studies that have claimed the global CO2 concentration decreased during the first wave of the COVID-19 pandemic. There are two ways to measure the global CO2 concentration: from the top-down using satellites and the bottom-up using ground stations. We implemented the time-series analysis by comparing the before and after the inflection point (first wave of COVID-19) with the long-term CO2 concentration data obtained from World Meteorological Organization Global Atmosphere Watch (WMO GAW) and Greenhouse Gases Observing Satellite (GOSAT). Measurements from the GOSAT and GAW global monitoring stations show that the CO2 concentrations in Europe, China, and the USA have continuously risen in March and April 2020 compared with the same months in 2019. These data confirm that the global lockdown during the first wave of the COVID-19 pandemic did not change the vertical CO2 profile at the global level from the ground surface to the upper layer of the atmosphere. The results of this study provide an important foundation for the international community to explore policy directions to mitigate climate change in the upcoming post-COVID-19 period.


[Effect of Corynebacterium parvum on serum lysozyme (muramidase) levels (author's transl)].
An i.v. injection of 548 microgram of killed Corynebacterium parvum into C57B1 mice leads to significant changes in serum lysozyme (muramidase) levels. After an initial fall at 24 h, the activity of the enzyme increased progressively, reached a peak on the 9th day and returned to control range after the 15th day.


Do sociodemographic and clinical factors affect the selection of initial antidepressant treatment for depression in older adults? Results from a nationwide descriptive study in Denmark.
The choice of antidepressants for initial pharmacological treatment of depression in older adults and associated patients' characteristics are understudied. We aimed to describe the first selected antidepressant (first-choice) for depression in older adults (≥65 years) and whether patients' sociodemographic and clinical characteristics influence selecting an alternative first-choice (any other antidepressant than the nationally recommended first-choice sertraline) in Denmark. Register-based cross-sectional study including all older adults who redeemed their first antidepressant prescription for depression at community pharmacies in Denmark in 2015-2019. We analyzed the effect of patients' characteristics on the first-choice antidepressant selection using multinomial logistic regression. Among 34,337 older adults with a first antidepressant-prescription, over two-thirds filled alternative first-choice antidepressants than sertraline (28.9 %): escitalopram or citalopram (30.3 %) or mirtazapine (34.4 %). Socially disadvantaged older adults (e.g., with short educational attainment, being single, or of non-western ethnicity) and clinically vulnerable older adults (e.g., having somatic diagnoses and hospital contacts) were more likely to use alternative first-choice antidepressants. Information on prescribers and in-hospital medications was not included in this study. Further investigation of the first antidepressant selection and its impact on depression treatment outcomes in older adults is necessary. Moreover, for older patients, national guidelines on depression treatment should be more specific. Antidepressant selection for initial pharmacological treatment of depression in older adults can be difficult due to comorbidity, polypharmacy, and age-related changes in pharmacokinetics and pharmacodynamics. Real-world evidence/knowledge on first-choice antidepressant selection and associated user characteristics are rare. This Danish register-based cross-sectional study found over two-thirds of older adults filled alternative antidepressants (primarily escitalopram/citalopram or mirtazapine) than nationally recommended first-choice sertraline for depression treatment and identified wide-ranging sociodemographic and clinical factors influencing the first antidepressant selection.


Lymphocyte subsets in the blood. The influence of splenectomy, splenic autotransplantation, ageing, and the site of blood sampling on the number of B, T, CD4+, and CD8+ lymphocytes in the rat.
Removal of the largest single lymphoid organ, the spleen, leads to an increase in severe infections. To prevent this, transplantation of splenic fragments can be performed, which may, however, cause an increase in CD8+ lymphocytes in the blood of these patients. This is controversial since in the clinical situation it is often difficult to account for the different age of the patients, the time point after the operation and many other factors known to influence the number of lymphocyte subsets. Using a well-defined animal model, B, T, CD4+, and CD8+ lymphocytes were determined preoperatively in adult rats. Then, either sham splenectomy, splenectomy, or splenic autotransplantation was performed and the animals were followed up for 15 months after the operation. The surgical procedure itself, the site of blood sampling and ageing all influenced the number of lymphocyte subsets profoundly. Furthermore, giving the data as relative or absolute numbers leads to different results. Splenectomy caused lymphocytosis, due to a significant increase in B and CD8+ lymphocytes, as did splenic autotransplantation, which indicates that the number of lymphocyte subsets in the blood should not be used to argue in favour of or against splenic autotransplantation. This study demonstrates that the number of lymphocyte subsets in the blood is influenced by many factors and therefore should be determined in a highly standardized fashion.