Unusually Large Effects of Charge-assisted C-H⋅⋅⋅F Hydrogen Bonds to Anionic Fluorine in Organic Solvents: Computational Study of 19 F NMR Shifts versus Thermochemistry.
A comparison of computed 19 F NMR chemical shifts and experiment provides evidence for large specific solvent effects for fluoride-type anions interacting with the σ*(C-H) orbitals in organic solvents like MeCN or CH2 Cl2 . We show this for systems ranging from the fluoride ion and the bifluoride ion [FHF]- to polyhalogen anions [ClFx ]- . Discrepancies between computed and experimental shifts when using continuum solvent models like COSMO or force-field-based descriptions like the 3D-RISM-SCF model show specific orbital interactions that require a quantum-mechanical treatment of the solvent molecules. This is confirmed by orbital analyses of the shielding constants, while less negatively charged fluorine atoms (e. g., in [EF4 ]- ) do not require such quantum-mechanical treatments to achieve reasonable accuracy. The larger 19 F solvent shift of fluoride in MeCN compared to water is due to the larger coordination number in the former. These observations are due to unusually strong charge-assisted C-H⋅⋅⋅F- hydrogen bonds, which manifest beyond some threshold negative natural charge on fluorine of ca. < -0.6 e. The interactions are accompanied by sizable free energies of solvation, in the order F- ≫[FHF]- >[ClF2 ]- >[ClF4 ]- . COSMO-RS solvation free energies tend to moderately underestimate those from the micro-solvated cluster treatment. Red-shifted and intense vibrational C-H stretching bands, potentially accessible in bulk solution, are further spectroscopic finger prints.


An attempt to develop a database for epidemiological research in Semipalatinsk.
The present paper reports progress and problems in our development of a database for comprehensive epidemiological research in Semipalatinsk whose ultimate aim is to examine the effects of low dose radiation exposure on the human body. The database was constructed and set up at the Scientific Research Institute of Radiation Medicine Ecology in 2003, and the number of data entries into the database reached 110,000 on 31 January 2005. However, we face some problems concerning size, accuracy and reliability of data which hinder full epidemiological analysis. Firstly we need fuller bias free data. The second task is to establish a committee for a discussion of the analysis, which should be composed of statisticians and epidemiologists, to conduct a research project from a long-term perspective, and carry out the collection of data effectively, along the lines of the project. Due to the insufficiency of data collected so far, our analysis is limited to showing the trends in mortality rates in the high and low dose areas.


Cryptogenic Organizing Pneumonia Presenting as a Solitary Mass: Clinical, Imaging, and Pathologic Features.
BACKGROUND Cryptogenic organizing pneumonia (COP), with a variety of radiologic findings, is a clinical pathological entity characterized by the presence of granulation tissue composed of fibroblasts/myofibroblasts and loose connective tissue in the alveoli and/or the distal bronchioles. Nevertheless, the presence of a solitary mass in COP is relatively rare. This study investigated the clinical, imaging, and pathologic features of COP with solitary mass form. MATERIAL AND METHODS This retrospective analysis included 12 patients (9 men and 3 women; age range 36-78 years; mean age 60±9 years) with surgery- or biopsy-proven COP with a solitary lung mass, diagnosed between June 2012 and December 2017 at the Department of Radiology in our hospital. RESULTS All patients experienced cough with expectoration and 8 patients had hemoptysis. All lesions were adjacent to the pleura. Mean size of the lesions was 4.2±0.9 cm (range, 3.2-6.1 cm). The upper left lobe was the site of the lesion in 4 patients. Six masses had heterogeneous density; among these, 4 had cavities and distal obstructive inflammation. The mass caused pleural indentation in 4 patients. Lymphadenopathy was seen in 7 patients. All specimens showed buds of granulation tissue within the lumen of the distal pulmonary airspaces, with significant increase in interstitial lymphocytes in 4 specimens. CONCLUSIONS Patients with COP with solitary mass form are more susceptible to hemoptysis and the mass is prone to necrosis. Vascular bundles, exudation around the mass, interstitial lymphocyte infiltration, and mediastinal lymph node enlargement are common features.


Role of blood components in ocular silicone oil emulsification. Studies on an in vitro model.
To develop an in vitro model for silicone oil emulsification and to explore the blood components involved in this process. The capacity of various blood components to support silicone oil (1000 CS) emulsification was studied by applying 0.5 ml oil on top of 0.5 ml saline containing various blood components. Each tube was sonicated for 150 seconds and centrifuged at 5000 g for 20 minutes. Three phases were noted in the tube: At the top was clear silicone oil, in the middle was emulsified silicone oil, and at the bottom was aqueous solution. The tubes were photographed, and the percentage of the phase length containing emulsified silicone oil (middle) of the total length of the three phases was calculated from the projected image of each tube. Emulsified silicone oil in plasma or serum was initiated after 100 seconds of sonication and quickly reached maximum (approximately 80%) at 120 seconds. The size of these oil droplets prepared in vitro was 0.0467 +/- 0.028 mm, closely resembling that observed in oil samples removed from a patient's anterior chamber (0.038 +/- 0.018 mm). Under these conditions, silicone oil emulsified in the presence of whole blood cells occurred only at a concentration of 120 micrograms protein/ml; in the presence of red blood cell membranes, it occurred at a concentration of 60 micrograms protein/ml. Lipoprotein-deficient serum failed to support emulsification; however, samples of high-density lipoprotein and low-density lipoprotein supported this process. Purified high-density lipoprotein-apolipoproteins supported oil emulsification. The addition of phosphatidylcholine further enhanced this process, but phosphatidylcholine alone failed to support emulsification. A simple and fast in vitro model to study factors affecting silicone oil emulsification was developed. Using this model, red blood cell membranes, plasma lipoproteins, and purified HDL-apolipoproteins supported silicone oil emulsification. Lipids did not, but they had the capacity to enhance the apolipoprotein-supported emulsification.


Computers in dental education. Promise of the past versus reality of the present.
Computer usage in dental education has a history of about three decades. As envisioned during the infant years, this application has fallen considerably short of expectations, especially regarding instructional applications. The authors trace the early years through the present project a realistic view of computer-based usage in dental education in the coming years.


Apolipoprotein A-IV is a novel substrate for matrix metalloproteinases.
Screening of matrix metalloproteinase (MMP)-14 substrates in human plasma using a proteomics approach previously identified apolipoprotein A-IV (apoA-IV) as a novel substrate for MMP-14. Here, we show that among the tested MMPs, purified apoA-IV is most susceptible to cleavage by MMP-7, and that apoA-IV in plasma can be cleaved more efficiently by MMP-7 than MMP-14. Purified recombinant apoA-IV (44-kDa) was cleaved by MMP-7 into several fragments of 41, 32, 29, 27, 24, 22 and 19 kDa. N-terminal sequencing of the fragments identified two internal cleavage sites for MMP-7 in the apoA-IV sequence, between Glu(185) and Leu(186), and between Glu(262) and Leu(263). The cleavage of lipid-bound apoA-IV by MMP-7 was less efficient than that of lipid-free apoA-IV. Further, MMP-7-mediated cleavage of apoA-IV resulted in a rapid loss of its intrinsic anti-oxidant activity. Based on the fact that apoA-IV plays important roles in lipid metabolism and possesses anti-oxidant activity, we suggest that cleavage of lipid-free apoA-IV by MMP-7 has pathological implications in the development of hyperlipidemia and atherosclerosis.


Glycogen granules in resting and inflammatory rainbow trout phagocytes--an ultrastructural study.
The ultrastructural image of glycogen granules in the cytoplasm of rainbow trout phagocytes in sections stained by the conventional lead or uranyl-lead stains is highly dependent on fixation conditions, the granules being visible only when adequate fixation protocols are used. Morphometry of samples processed for the detection of peroxidase or esterase activities (to specifically label neutrophils and macrophages, respectively), and simultaneously stained for the specific detection of glycogen, showed that inflammatory peritoneal neutrophils were richer in glycogen granules than resting neutrophils. This increase in glycogen content occurs after the migration from the haematopoietic tissues and peripheral blood to the inflamed foci. Glycogen granules could not be found in resting peritoneal macrophages but were found in inflammatory macrophages. The macrophage granules occurred in smaller amounts than in neutrophils, and consisted of granules identical to those of neutrophils together with significantly smaller granules. No evidence for the utilization of glycogen by neutrophils phagocytosing bacteria within the peritoneal cavity was found.


A Comparison of Antibacterial Efficacy of 0.5% Sodium Fluoride Impregnated Miswak and Plain Miswak Sticks on Streprococcus mutans - A Randomized Controlled Trial.
Miswak (Salvadora persica) is a tooth cleaning stick made from the Salvodora Persica tree. It serves as a natural dentifrice with anti-bacterial, anti-plaque and anti-fungal properties. Fluoride, impregnated in chewing sticks will bestow comparable safety against dental caries as the fluoride containing dentifrice. The aim of the present study was to assess and compare the anti-bacterial effect of 0.5% sodium fluoride impregnated miswak and plain miswak sticks on Streptococcus mutans. A randomized controlled concurrent parallel triple blind clinical trial was conducted for a period of 8 days. The trial included 30 subjects aged 20-23 years, who were randomly allocated in 1:1 ratio to Group A [0.5% Sodium Fluoride (NaF) impregnated Miswak sticks) and Group B (Plain Miswak sticks) respectively. The participants were instructed to chew miswak sticks for 6 minutes in the morning before breakfast. Unstimulated saliva was collected at baseline and after chewing miswak sticks to estimate S. mutans count using Mitis Salivarius Bacitracin agar. Data was statistically analyzed using paired and unpaired t-test. A statistically significant reduction in S. mutans Colony Forming Units (CFU) count in saliva was observed after using fluoridated miswak sticks compared to the baseline count (p=0.001). There was no significant difference in anti-bacterial effect of fluoridated miswak sticks and plain miswak sticks on S. mutans count (p=0.58). The efficacy of miswak impregnated with 0.5% NaF and plain miskaw sticks in reducing S. mutans counts in saliva is analogous.


Cyclic hydrostatic pressure enhances the chondrogenic phenotype of human mesenchymal progenitor cells differentiated in vitro.
Much attention has been given to the influences of bioactive factors on mesenchymal progenitor cell differentiation and proliferation, but few studies have examined the effect of mechanical factors on these cells. This study examined the effects of cyclic hydrostatic pressure on human bone marrow-derived mesenchymal progenitor cells undergoing chondrogenic differentiation. Aggregates of bone marrow-derived mesenchymal progenitor cells were cultured in a defined chondrogenic medium and were subjected to cyclic hydrostatic pressure. Aggregates were loaded at various time points: single (day 1 or 3) or multiple (days 1-7). At 14 and 28 days, aggregates were harvested for histology, immunohistochemistry, and quantitative DNA and matrix macromolecule analysis. The aggregates loaded for a single day did not demonstrate significant changes in proteoglycan and collagen contents compared with the non-loaded controls. In contrast, for the multi-day loaded aggregates, statistically significant increases in proteoglycan and collagen contents were found on both day 14 and day 28. Aggregates loaded for seven days were larger and histological staining indicated a greater matrix/cell ratio. This study indicates that hydrostatic pressure enhances the cartilaginous matrix formation of mesenchymal progenitor cells differentiated in vitro, and suggests that mechanical forces may play an important role in cartilage repair and regeneration in vivo.


Examination of multiple sources of selenium release from coal wastes and strategies for remediation.
Selenium (Se) has been mobilised by leaching from coal and associated waste rock exposed by mining activities in Western Canada, with deleterious impact on aquatic wildlife. Waste rock characterisation indicates that up to 7% of the Se, as Se(IV), may be associated with organic matter, with ≈9%, as Se(0), associated with euhedral pyrite. Small 1-2 µm mineral particles with average Se concentration of 1.0 ± 0.4 wt% account for the remaining Se with the largest components likely to be associated with Fe oxide/hydroxide/carbonate as Se(0) and framboidal pyrite as Se(IV) and Se(0). No evidence was found for the presence of Se(-I), Se(-II) or Se(VI). In the first 8 weeks of leaching Se release was not correlated to the addition of aqueous silicate, added to aid pyrite passivation, but was reduced by approximately one third when the waste was treated with manure. This suggests the primary initial source of leached Se was not pyrite. Added organic C results in increased microbial numbers, particularly aerobic microbes, and promotes the formation of extensive coating of extracellular polymeric substances resulting in depletion of O2 at particle surfaces, reducing oxidation of Se(IV) and therefore reducing the leach rate of Se. Subsequent to 8 weeks of leaching the rates of release of Se from the treated wastes were similar regardless of treatment strategy but were reduced as compared to the untreated waste rock, suggestive of partial framboidal pyrite geochemical and microbial passivation. Se leaching was not correlated to S leaching, but the source(s) of the leached S was not known as approximately half of the S within the waste rock was non-sulfidic. These results indicate that utilisation of local organic carbon-containing wastes for coverage of coal waste rock may be a cost-effective strategy to reduce Se leaching to acceptable rates of release regardless of whether the Se is associated with framboidal pyrite or organics.


Genetic structuring and recent demographic history of red pandas (Ailurus fulgens) inferred from microsatellite and mitochondrial DNA.
Clarification of the genetic structure and population history of a species can shed light on the impacts of landscapes, historical climate change and contemporary human activities and thus enables evidence-based conservation decisions for endangered organisms. The red panda (Ailurus fulgens) is an endangered species distributing at the edge of the Qinghai-Tibetan Plateau and is currently subject to habitat loss, fragmentation and population decline, thus representing a good model to test the influences of the above-mentioned factors on a plateau edge species. We combined nine microsatellite loci and 551 bp of mitochondrial control region (mtDNA CR) to explore the genetic structure and demographic history of this species. A total of 123 individuals were sampled from 23 locations across five populations. High levels of genetic variation were identified for both mtDNA and microsatellites. Phylogeographic analyses indicated little geographic structure, suggesting historically wide gene flow. However, microsatellite-based Bayesian clustering clearly identified three groups (Qionglai-Liangshan, Xiaoxiangling and Gaoligong-Tibet). A significant isolation-by-distance pattern was detected only after removing Xiaoxiangling. For mtDNA data, there was no statistical support for a historical population expansion or contraction for the whole sample or any population except Xiaoxiangling where a signal of contraction was detected. However, Bayesian simulations of population history using microsatellite data did pinpoint population declines for Qionglai, Xiaoxiangling and Gaoligong, demonstrating significant influences of human activity on demography. The unique history of the Xiaoxiangling population plays a critical role in shaping the genetic structure of this species, and large-scale habitat loss and fragmentation is hampering gene flow among populations. The implications of our findings for the biogeography of the Qinghai-Tibetan Plateau, subspecies classification and conservation of red pandas are discussed.


Succinylcholine Use and Dantrolene Availability for Malignant Hyperthermia Treatment: Database Analyses and Systematic Review.
Although dantrolene effectively treats malignant hyperthermia (MH), discrepant recommendations exist concerning dantrolene availability. Whereas Malignant Hyperthermia Association of the United States guidelines state dantrolene must be available within 10 min of the decision to treat MH wherever volatile anesthetics or succinylcholine are administered, a Society for Ambulatory Anesthesia protocol permits Class B ambulatory facilities to stock succinylcholine for airway rescue without dantrolene. The authors investigated (1) succinylcholine use rates, including for airway rescue, in anesthetizing/sedating locations; (2) whether succinylcholine without volatile anesthetics triggers MH warranting dantrolene; and (3) the relationship between dantrolene administration and MH morbidity/mortality. The authors performed focused analyses of the Multicenter Perioperative Outcomes Group (2005 through 2016), North American MH Registry (2013 through 2016), and Anesthesia Closed Claims Project (1970 through 2014) databases, as well as a systematic literature review (1987 through 2017). The authors used difficult mask ventilation (grades III and IV) as a surrogate for airway rescue. MH experts judged dantrolene treatment. For MH morbidity/mortality analyses, the authors included U.S. and Canadian cases that were fulminant or scored 20 or higher on the clinical grading scale and in which volatile anesthetics or succinylcholine were given. Among 6,368,356 queried outcomes cases, 246,904 (3.9%) received succinylcholine without volatile agents. Succinylcholine was used in 46% (n = 710) of grade IV mask ventilation cases (median dose, 100 mg, 1.2 mg/kg). Succinylcholine without volatile anesthetics triggered 24 MH cases, 13 requiring dantrolene. Among 310 anesthetic-triggered MH cases, morbidity was 20 to 37%. Treatment delay increased complications every 10 min, reaching 100% with a 50-min delay. Overall mortality was 1 to 10%; 15 U.S. patients died, including 4 after anesthetics in freestanding facilities. Providers use succinylcholine commonly, including during difficult mask ventilation. Succinylcholine administered without volatile anesthetics may trigger MH events requiring dantrolene. Delayed dantrolene treatment increases the likelihood of MH complications. The data reported herein support stocking dantrolene wherever succinylcholine or volatile anesthetics may be used.


A major fish stranding caused by a natural hypoxic event in a shallow bay of the eastern South Pacific Ocean.
A massive beaching and mortality of fishes occurred in Coliumo Bay, a shallow bay located along the coast of the eastern South Pacific Ocean on 3 January 2008. This stranding was a consequence of an abrupt decrease in the dissolved oxygen concentration throughout the whole water column, due to the effect of intense upwelling along the coast off central-southern Chile. The main objectives of this study were: (1) to characterize taxonomically and biologically the fish species assemblage present in this beaching; (2) to evaluate several physiological indicators for the condition of the beached species at the time of their death; and (3) to assess the possible cause-effect mechanisms involved in the fishes death and the changes that took place in the fish community throughout the time. In this beaching, 26 fish species were identified: 23 teleosts, one myxiniform and two elasmobranchs. Most beached specimens were juveniles. Haematological and histological evidence indicate that severe hypoxia that lasted for at least 48 h was the most plausible cause of death. The main conclusion of this study is that the presence of oxygen-poor equatorial sub-surface water in the shallow coastal zone due to intense regional-scale upwelling caused the fish stranding. Although the effect of the hypoxic event was severe for the fish assemblage of Coliumo Bay, the rapid recuperation observed suggests that hypoxic events at the local spatial scale can be buffered by migration processes from the fish community inhabiting close by areas non-affected by low oxygen conditions. The effect that severe hypoxic events may have on larger spatial scales remains unknown.


Exercise training lowers resting renal but not cardiac sympathetic activity in humans.
Endurance exercise training has previously been shown to reduce the plasma concentration of norepinephrine. Whether reduction in sympathetic activity is responsible for the blood pressure-lowering effects of exercise training is unknown. Using a radiotracer technique, we measured resting total, cardiac, and renal norepinephrine spillover to plasma in eight habitually sedentary healthy normotensive men (aged 36 +/- 3 years, mean +/- SEM) after 1 month of regular exercise and 1 month of sedentary activity, performed in a randomized order. One month of bicycle exercise 3 times/wk (40 minutes at 60-70% maximum work capacity) reduced resting blood pressure by 8/5 mm Hg (p less than 0.01) and increased maximum oxygen consumption by 15% (p less than 0.05). The fall in blood pressure was attributable to a 12.1% increase in total peripheral conductance. Total norepinephrine spillover to plasma was reduced by 24% from a mean of 438.8 ng/min (p less than 0.05). Renal norepinephrine spillover fell by an average of 41% from 169.4 ng/min with bicycle training (p less than 0.05), accounting for the majority (66%) of the fall in total norepinephrine spillover. Renal vascular conductance was increased by 10% (p less than 0.05), but this constituted only 18% of the increase in total peripheral conductance. There was no change in cardiac norepinephrine spillover. The reduction in resting sympathetic activity with regular endurance exercise is largely confined to the kidney. The magnitude of the fall in renal vascular resistance, however, is insufficient to directly account for the blood pressure-lowering effect of exercise, although other effects of inhibition of the renal sympathetic outflow may be important.


Delay of cleavage of the Arbacia egg by ultraviolet radiation.
While our data do not permit us to state the exact locus or mode of action of ultraviolet radiation in the Arbacia egg, certain general conclusions may be reached. The amount of delay of cleavage of these eggs is determined by two principal factors: (1) The extent of an effect, resulting from photochemical action induced by ultraviolet radiation, which is reversible in a biological sense, the reversibility not being directly dependent upon the process of cell division. (2) The sensitivity of the cell division process to the effects of the ultraviolet-induced photochemical reaction. This factor varies with the stage of cell division, the cell being insensitive during a period corresponding to most of mitosis. It seems likely that these findings may apply to cell division in general, but, since the quantitative relationships observed must, in this case, reflect the integration of two semi-independent factors, the over-all picture may appear quite different for different kinds of cells.


The Unique Relationship between Neuro-Critical Care and Critical Illness-Related Corticosteroid Insufficiency : Implications for Neurosurgeons in Neuro-Critical Care.
The brain houses vital hormonal regulatory structures such as the hypothalamus and pituitary gland, which may confer unique susceptibilities to critical illness-related corticosteroid insufficiency (CIRCI) in patients with neurological disorders. In addition, the frequent use of steroids for therapeutic purposes in various neurological conditions may lead to the development of steroid insufficiency. This abstract aims to highlight the significance of understanding these relationships in the context of patient care and management for physicians. Neurological disorders may predispose patients to CIRCI due to the role of the brain in hormonal regulation. Early recognition of CIRCI in the context of neurological diseases is essential to ensure prompt and appropriate intervention. Moreover, the frequent use of steroids for treating neurological conditions can contribute to the development of steroid insufficiency, further complicating the clinical picture. Physicians must be aware of these unique interactions and be prepared to evaluate and manage patients with CIRCI and steroid insufficiency in the context of neurological disorders. This includes timely diagnosis, appropriate steroid administration, and careful monitoring for potential adverse effects. A comprehensive understanding of the interplay between neurological disease, CIRCI, and steroid insufficiency is critical for optimizing patient care and outcomes in this complex patient population.


Field-enhanced selectivity in nanoconfined ionic transport.
Fluid transport confined in nanochannels shows ultrafast permeation and highly efficient separation performance. However, the size-controlled selectivity of hydrated ions with a similar valence and size, such as alkali ions, is well below 5. We propose in this work to boost ion selectivity through the interaction with the wall of flow channels, which can be enhanced by applying an external electric field across the channel. Molecular simulations show that for ions diffusing near the walls of a graphene nanochannel, the hydration shells are perturbed, endowing the contrast in ion-wall interactions to modify the ion-specific free energy landscape. The trapping/hopping nature of ion diffusion near the wall leads to the conclusion that the diffusivity depends on the free energy barriers rather than the hydration size. This effect can be magnified by elevating the field strength, yielding more than ∼10-fold enhancement in the diffusivity-specific selectivity. With recent experimental advances in external electric field control and local electric field modulation near the surface, this work demonstrates a possible route to achieve high selectivity of alkali ions in nanofluidics, and explore the molecular structures and dynamics of hydrated ions near a surface.


Evaluation of an implanted osmotic pump for delivery of amikacin to corn snakes (Elaphe guttata guttata).
The risk of accidental envenomation to the handler of venomous snakes during drug administration limits the ability to treat these animals. One commercially available osmotic pump is a miniature self-contained cylindrical implant that operates on the basis of an osmotic pressure difference between the extracellular fluid and the osmotic agent in the pump. Osmotic pumps loaded with amikacin were surgically placed into the coelomic cavity of five adult corn snakes (Elaphe guttata guttata) (group A). Four snakes (group B) received an intramuscular injection of amikacin at 5 mg/kg followed by 2.5 mg/kg q 72 hr for a total of four injections. Plasma concentrations of amikacin were measured in both groups. Renal function was evaluated pre- and posttreatment via scintigraphy with 99mTc-mercaptoacetyltriglycine (99mTc-MAG3) and measurement of plasma uric acid concentrations. Mean (+/- SD) steady state amikacin concentration for group A was 6.9 +/- 1.7 microg/ml (predicted = 8.0 microg/ml), and the measured pump rate was 0.134 +/- 0.017 microl/hr (predicted = 0.130 microl/hr). Mean (+/- SD) peak and trough plasma amikacin concentrations for group B were 22.7 +/- 8.5 microg/ml and 14.3 +/- 7.0 microg/ml, respectively. While neither scintigraphy nor plasma uric acid concentrations indicated toxicity in either group, continuous administration of aminoglycosides may cause nephrotoxicity, and it is unknown whether this delivery method of amikacin would be efficacious in treating bacterial infections in snakes. In addition, due to migration of one pump into the trachea causing asphyxiation and death, these pumps may not be appropriate for intracoelomic placement in corn snakes. Nonetheless, the pumps delivered the drug at a predictable rate and were efficacious in achieving a constant plasma concentration of amikacin at the predicted level. Osmotic pumps may offer a safer alternative to periodic intramuscular injections for drug delivery in venomous or aggressive snakes.


The Importance of Controlled Mismatch of Biomechanical Compliances of Implantable Scaffolds and Native Tissue for Articular Cartilage Regeneration.
Scaffolds for articular cartilage repair have to be optimally biodegradable with simultaneous promotion of hyaline cartilage formation under rather complex biomechanical and physiological conditions. It has been generally accepted that scaffold structure and composition would be the best when it mimics the structure of native cartilage. However, a reparative construct mimicking the mature native tissue in a healing tissue site presents a biological mismatch of reparative stimuli. In this work, we studied a new recombinant human type III collagen-polylactide (rhCol-PLA) scaffolds. The rhCol-PLA scaffolds were assessed for their relative performance in simulated synovial fluids of 1 and 4 mg/mL sodium hyaluronate with application of model-free analysis with Biomaterials Enhanced Simulation Test (BEST). Pure PLA scaffold was used as a control. The BEST results were compared to the results of a prior in vivo study with rhCol-PLA. Collectively the data indicated that a successful articular cartilage repair require lower stiffness of the scaffold compared to surrounding cartilage yet matching the strain compliance both in static and dynamic conditions. This ensures an optimal combination of load transfer and effective oscillatory nutrients supply to the cells. The results encourage further development of intelligent scaffold structures for optimal articular cartilage repair rather than simply trying to imitate the respective original tissue.


Circulating microRNAs as Biomarkers of Radiation Exposure: A Systematic Review and Meta-Analysis.
MicroRNAs (miRNAs) were hypothesized to be robust and easily measured biomarkers of radiation exposure, which has led to multiple studies in various clinical and experimental scenarios. We sought to identify evolutionary conserved, radiation-induced circulating miRNAs through a multispecies, integrative systematic review and meta-analysis of miRNAs in radiation. The systematic review was registered in the PROSPERO database (ID: 81701). We downloaded a list of studies with the query: (circulating OR plasma OR serum) AND (miRNA or microRNA) AND (radiat* OR radiotherapy OR irradiati*) from MEDLINE (103 studies), EMBASE (364 studies), and Cochrane Database of Systematic Reviews (0 studies). After deleting 116 duplicates, the remaining 351 abstracts were reviewed. Inclusion criteria were experimental study; human, mice, rat or nonhuman primate study; and serum or plasma miRNA expression measured before and after radiation exposure. The screening procedure yielded 62 research studies. After verification, 30 articles contained data on miRNA expression change after irradiation. Thus, we obtained a database of 131 miRNAs from 96 pairwise post-/preirradiation comparisons reporting 2508 fold changes (FCs) of circulating miRNAs. The meta-analysis showed 28 miRNAs with significant radiation-induced change of their expression in the serum. In metaregression analysis, 7 miRNAs-miR-150 (FC = 0.40; 95% confidence interval [CI], 0.35-0.45), miR-29a (FC = 0.87; 95% CI, 0.79-0.96), miR-29b (FC = 0.85; 95% CI, 0.76-0.96), miR-30c (FC = 1.19; 95% CI, 1.09-1.30), miR-200b (FC = 1.34; 95% CI, 1.21-1.48), miR-320a (FC = 1.13; 95% CI, 1.05-1.23), and miR-30a (FC = 1.18; 95% CI, 1.07-1.30)-significantly correlated with either total or fraction dose of radiation. Additionally, miR-150, miR-320a, miR-200b, and miR-30c correlated significantly with time elapsed since irradiation. Circulating miRNAs reflect the impact of ionizing radiation irrespective of the studied species, often in a dose-dependent manner. This makes circulating miRNAs promising biomarkers of radiation exposure.


Managing acute opioid withdrawal with tramadol during COVID-19 lockdown in a peri-urban setting.
The coronavirus disease 2019 (COVID-19) has highlighted the scope of heroin dependence and need for evidence-based treatment amongst marginalised people in South Africa. Acute opioid withdrawal management without maintenance therapy carries risks of increased morbidity and mortality. Due to the high costs of methadone, Tshwane's Community Oriented Substance Use Programme (COSUP) used tramadol for opioid withdrawal management during the initial COVID-19 response. To describe demographics, route of heroin administration and medication-related experiences amongst people accessing tramadol for treatment of opioid withdrawal. Three community-based COSUP sites in Mamelodi (Tshwane, South Africa). A retrospective cross-sectional study was conducted. Data were collected using an interviewer-administered paper-based tool between April and August 2020. Descriptive statistics were used to analyse data. Of the 220 service users initiated onto tramadol, almost half (n = 104, 47%) were not contactable. Fifty-eight (26%) people participated, amongst whom most were male (n = 55, 95%). Participants' median age was 32 years. Most participants injected heroin (n = 36, 62.1%). Most participants experienced at least one side effect (n = 47, 81%) with 37 (64%) experiencing two or more side effects from tramadol. Insomnia occurred most frequently (n = 26, 45%). One person without a history of seizures experienced a seizure. Opioid withdrawal symptoms were experienced by 54 participants (93%) whilst taking tramadol. Over half (n = 38, 66%) reported using less heroin whilst on tramadol. Tramadol reduced heroin use but was associated with withdrawal symptoms and unfavourable side effects. Findings point to the limitations of tramadol as opioid withdrawal management to retain people in care and the importance of access to first-line opioid agonists.Contribution: This research contributes to the limited data around short-acting tramadol for opioid withdrawal management in the African context, with specific focus on the need for increased access to opioid agonists for those who need them, in primary care settings.


Validity of an activities of daily living questionnaire among older patients in the emergency department.
The objective of this study was to determine the validity of French and English versions of the Older American Resources and Services (OARS) activities of daily living (ADL) questionnaire using a premorbid reference period among older emergency department (ED) patients. A sample of 404 ED patients aged 65 and over participating in a study of functional decline was invited to participate in a clinical assessment shortly after their ED visit. The OARS ADL questionnaire was administered either to the patient or a proxy informant at the ED visit. The clinical assessment was conducted by a nurse, blind to the OARS score, using the Functional Autonomy Measurement System (SMAF). Disability scores for the OARS and SMAF were computed, based on the patient's premorbid status. Assessments were conducted in 213 patients (52.7%). The OARS summary scores, a total and an ordinal score, were highly correlated with the SMAF total disability score (Spearman's r of 0.80 and 0.79, respectively). Similar correlations were found for French and English versions. The OARS ADL questionnaire with a premorbid reference period appears to be valid when administered in the ED, both in French and English.


Analysis of the implementation of a personalized care model in diabetes mellitus as an example of chronic disease with information and communication technology support.
Diabetes mellitus affects 13.8% of the adult population in Spain, representing some 8.2% of total Spanish health spending, which may be reduced by optimizing treatment and disease monitoring. Areas covered: This perspective article aims to evaluate the possible clinical and economic outcomes of implementing a theoretical personalized care model in diabetes supported by information and communications technology in Spain vs. conventional care. Moreover, we assessed the value of emminens® eConecta, a solution designed to support the operational implementation of this model, which enables the connection and participation of patients and health professionals, facilitates patient education, decision-making, access to information, and data analysis. We carried out a review of the available evidence, consultations with experts and a clinical and cost estimation. Expert commentary: The experts consulted considered that the proposed model is consistent with Spanish strategies on chronicity, supports the management of chronicity/diabetes, and may improve the most important aspects of disease management. In the literature, this type of care models improved or provided equal disease control compared with conventional care, potentiated self-management strategies and reduced the high use of resources. Cost estimation showed a reduction of -12% in total direct costs and around -34% in the costs of outpatient visits.


Effects of prostaglandin E2 on the newborn respiratory system.
To test the hypothesis that prostaglandin (PG) E2 is a respiratory depressant in the newborn lamb, 12 chronically catheterized, unanesthetized lambs (age 2 to 6 days) were infused with progressively increasing doses of PGE2 (0.1, 0.5, 1.0 and 5.0 ug/kg/min: 30 min for each dose) into the ascending aorta. PGE2 caused significant, progressive decrease in ventilation (due to decreased tidal volume and breathing rate) heart rate, blood pressure and percent of the time spent in low voltage electrocortical activity (LVA). PGE2 also caused respiratory acidosis, hypoxemia and increased frequency and duration of apneic events (greater than 3 sec). During the infusion, there was a dose related increase in plasma concentration of PGE2. At 30 min post-infusion, all measured variables showed recovery, although arterial pH carbon dioxide tension and plasma PGE2 remained significantly different from control values and the percent time in LVA was even higher than during control. Infusion of the vehicle alone (n = 5) caused no significant changes in any of the measured variables. The results, taken in combination with previous fetal studies, indicate that PGE2 has marked inhibitory effects on breathing movements both before and after birth.


Tooth loss is associated with increased risk of gastric non-cardia adenocarcinoma in a cohort of Finnish smokers.
Tooth loss has been associated with upper gastrointestinal cancer in several studies, but only one previous study used prospectively collected data. The importance of confounding by Helicobacter pylori has not previously been addressed. The objective was to determine the association between tooth loss and upper gastrointestinal cancer in the Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study cohort and to determine the importance of potentially confounding dietary factors or H. pylori seropositivity. A prospective cohort study with 29,124 subjects included 49 esophageal squamous cell carcinomas, 66 esophageal/gastric cardia adenocarcinomas, and 179 gastric non-cardia adenocarcinomas occurring between 1985 and 1999. Cox proportional hazards models adjusted for age and education were used to estimate hazard ratios (HRs) and 95% CIs. Odds ratios and 95% CIs were calculated with and without adjustment for H. pylori seropositivity in a nested case-control group to determine whether H. pylori confounded the association between tooth loss and gastric cancer. Tooth loss significantly increased the hazard ratio for gastric non-cardia cancer, the HR (95% CI) for edentulous subjects versus those with < 10 teeth lost was 1.65 (1.09, 2.49, respectively). No statistically significant associations were found between tooth loss and esophageal squamous cell carcinoma or esophageal/gastric cardia adenocarcinoma. Confounding by dietary factors, tobacco smoking, or H. pylori did not explain these results. Tooth loss was associated with increased risk of gastric non-cardia cancer, but not esophageal squamous cell carcinoma or esophageal/gastric cardia adenocarcinoma in this Finnish cohort.


Educating entry-level occupational therapy students in gerontology.
The need for gerontic occupational therapists is increasing as the number of elders increases. The practice of including gerontologic content in occupational therapy entry-level curricula is relatively new. This article provides a rationale for including gerontologic content in entry-level occupational therapy curricula and presents the results of a brief survey conducted in November 1990 of all accredited and developing entry-level professional occupational therapy programs in the United States. Seventy-one percent of the entry-level programs responded. All of the responding programs included some gerontologic content in their curricula, and 82% of the responding programs indicated that the amount of gerontologic content in the required curriculum had increased in the past 5 years. Other gerontologic elements examined were courses offered and topics included in entry-level curricula, textbooks used, and gerontic fieldwork requirements.


Hepatitis B virus X protein enhances the transcriptional activity of the androgen receptor through c-Src and glycogen synthase kinase-3beta kinase pathways.
Hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC) occurs predominantly in men. By enhancing the transcriptional activity of the androgen receptor (AR) gene in a ligand-dependent manner, the HBV X protein (HBx) might contribute to this disparity between sexes. To dissect the mechanisms underlying HBx-enhanced AR transactivation, we investigated the effect of HBx on two critical steps in the regulation of ligand-stimulated AR activities. One step is the dimerization of AR (through the interaction of its N-termini and C-termini), and the other step is the activation of the AR N-terminal transactivation domain (NTD). HBx increased the NTD activation of the AR through c-Src kinase. HBx also enhanced AR dimerization by inhibiting glycogen synthase kinase-3beta (GSK-3beta) activity, which acts as a negative regulator of the interaction between AR and the N-termini and C-termini. The HBx-enhanced AR transactivation was abolished by blocking c-Src and activating GSK-3beta kinases simultaneously, suggesting that these two kinases act as major switches in the activation process. The regulatory function of both kinases has been further verified in primary hepatocytes isolated from the livers of HBx transgenic male mice. Our study thus identified two key kinases through which HBx enhances the AR transcriptional activity. These kinases might be potential candidates for future prevention or therapy for HBV-related HCC in men.


Exposure to blood borne viruses and the hepatitis B vaccination status among healthcare workers in inner London.
Occupational exposure to blood borne viruses was examined during one year at a London teaching hospital. A total of 236 incidents occurred of which 83% were related to sharps, 32% were clearly avoidable, and 7% involved an infected source patient. Overall uptake of hepatitis B vaccine was 78% but it was particularly low in paramedical (70%) and domestic staff (45%). Continued effort needs to be applied to improve uptake of hepatitis B vaccine and to maintain high standards of control of infection.


Synthesis of first row transition metal selenomaltol complexes.
We report an efficient, one-step synthesis of the chelator 3-hydroxy-2-methyl-4-selenopyrone (selenomaltol). Complexes of selenomaltol with Fe(iii), Ni(ii), Cu(ii) and Zn(ii) have been prepared and studied by NMR, X-ray crystallography, cyclic voltammetry, EPR and electronic absorption. The Ni(ii) and Cu(ii) complexes show chemically reversible oxidations which are suggested to be ligand-based. Nuclear independent chemical shifts (NICS) analysis is used to compare aromaticity of the heterocyclic rings of selenomaltol and its chelates. The compounds described here should significantly expand the scope and utility of unusual O,Se-donor chelates.


The timing of learning before night-time sleep differentially affects declarative and procedural long-term memory consolidation in adolescents.
Sleep after learning has been shown to foster the consolidation of new memories. However, fundamental questions on the best timing of learning before night-time sleep persist. We tested the hypothesis that learning directly prior to night-time sleep compared to 7.5 hrs prior to night-time sleep provides better conditions for the consolidation of declarative and procedural memories. Fifty healthy female adolescents (aged 16-17 years) were trained on a declarative word-pair and a procedural finger-tapping task at 3 pm (afternoon group, n = 25) or at 9 pm (evening group, n = 25), followed by a sleep laboratory night. Retrieval was assessed 24 hours and 7 days after initial training. Subjects trained in the afternoon showed a significantly elevated retention rate of word-pairs compared to subjects trained in the evening after 24 hours, but not after 7 days. In contrast, off-line gains in finger-tapping performance were significantly higher in subjects trained in the evening compared to those trained in the afternoon after both retention intervals. The observed enhanced consolidation of procedural memories after training in the evening fits to current models of sleep-related memory consolidation. In contrast, the higher retention of declarative memories after encoding in the afternoon is surprising, appeared to be less robust and needs further investigation.


Preoperative serum potassium predicts the clinical outcome after non-cardiac surgery.
Potassium disorders have been linked to adverse outcomes in various medical conditions. However, the association of preoperative serum potassium with postoperative outcome is not well established. We aimed to examine the association between preoperative potassium with a 30-day mortality and adverse cardiovascular event (MACE). We conducted a cohort study using a prospectively collected database of patients, undergoing surgical procedures from 1998 to 2013 in the VA Western New York Healthcare System, which are reported to the Veterans Affairs Surgical Quality Improvement Program (VASQIP). The patients were categorized into three groups based on their documented preoperative potassium concentrations. Hypokalemia was defined as serum potassium concentration <4 mmol/L and hyperkalemia was defined as serum potassium concentrations >5.5 mmol/L. The values within the range of 4.0-5.5 mmol/L were considered as normokalemia and used as the control group. Statistical analyses included Chi-square test, analysis of variance and multivariate logistic regression to estimate the risk of MACE within 30 days of surgery. Study included 5959 veterans who underwent surgery between 1998 and 2013. The patients in the hyperkalemics group had lower kidney function compared to the other two groups. The frequency of MACE was 13.6% in hypokalemics and 21.9% in hyperkalemics that were both significantly higher than 4.9% in controls. In multivariate logistic regression the hazard risk (HR) ratios of MACE were (2.17, 95% CI 1.75-2.70) for hypokalemics and (3.23, 95% CI 2.10-4.95) for hyperkalemics when compared to normokalemic controls. Preoperative hypokalemia and hyperkalemia are both independent predictors of MACE within 30 days.


The use of antilymphocyte globulin in renal allograft rejection. A controlled study.
A controlled clinical investigation of the effect of equine anti-human-lymphocyte globulin (ALG) on established rejection after transplantation was carried out. In comparison with a control group, the treated group showed a significantly positive effect of ALG in the form of a faster reversal of rejection episodes (P less than 0-05). Leucocytes, lymphocytes, erythrocytes, thrombocytes and immunoglobulins were unaffected by the treatment, but there were signs of a complement consuming process and an influence on blast transformation tests. No rise in antibody titre against equine globulin was seen.


Hysteresis in cross-bridge models of muscle.
A dynamical system is said to exhibit hysteresis if its current state depends on its history. Muscle shows hysteretic properties at constant length, such as residual force enhancement after stretch. There is no generally accepted explanation for residual force enhancement. Here we examine a very simple kinetic model for the interaction between actin and myosin, the two main proteins involved in muscle contraction. We demonstrate that this model shows hysteresis at constant force. Since muscle is not a continuum but rather a group of repeating elements, called sarcomeres, arranged in series, we perform simulations of three sarcomeres. These simulations show hysteresis at constant length. This result is the first time that residual force enhancement has been demonstrated using an experimentally motivated kinetic model and multi-sarcomere simulations without passive elastic elements, damping and/or force-length relationships. We conclude by suggesting some experiments to test the model's predictions. If these experiments support the model, it becomes important to understand multiple sarcomere systems, since their behavior may be very different from most current simulations that neglect the coupling between sarcomeres.


Outcomes of circumcision in children with single ventricle physiology.
Children with single ventricle physiology (SVP) have been shown to have a high morbidity and mortality after non-cardiac surgical procedures. Elective circumcision is one of the most common pediatric operations with low morbidity and mortality. The purpose of our study was to review our institutional experience with SVP children undergoing circumcisions to determine peri-operative course and outcomes. We performed a retrospective review of children with SVP who underwent an elective circumcision from 2000 to 2017. Children with non-single ventricle physiology or children undergoing circumcision in combination with another case were excluded. Demographics, surgical characteristics, and outcomes were analyzed. Descriptive statistics were performed, all medians were reported with interquartile range. 15 males underwent elective circumcision with a median age at the time of surgery of 1.13 (1.03, 1.38) years. Eighty-four percent underwent their circumcision after their 2nd stage cardiac operation. Most common operative indication was uncomplicated phimosis. Median operative time was 20 (16, 27) mins. Median total length of stay was 229 (185, 242) mins with no admissions. Post-operative complications included two (16%) hematomas with one requiring surgical intervention. There were no deaths. Children with SVP who undergo elective circumcision may have a higher risk of bleeding.


The role of activin A and Akt/GSK signaling in ovarian tumor biology.
Elevated activin A levels in serum, cyst fluid, and peritoneal fluid of ovarian cancer patients suggest a role for this peptide hormone in disease development. We hypothesize that activin A plays a role in ovarian tumor biology, and analyzed activin-mediated pro-oncogenic signaling in vitro and the expression of activin signaling pathway molecules in vivo. Activin A regulation of Akt and GSK, and the effects of repressing the activities of these molecules (with pharmacological inhibitors) on cellular proliferation were assessed in the cell line, OVCA429. Activin A activated Akt, which phosphorylated GSK, repressing GSK activity in vitro. Activin A stimulated cellular proliferation and repression of GSK augmented activin-regulated proliferation. To validate in vitro observations, immunostaining of the betaA-subunit of activin A and phospho-GSKalpha/beta (Ser9/21) was performed, and the correlation between immunoreactivity levels of these markers and survival was evaluated in benign serous cystadenoma, borderline tumor, and cystadenocarcinoma microarrays. Analysis of tissue microarrays revealed that betaA expression in epithelia did not correlate with survival or malignancy, but expression was elevated in stromal cells from carcinomas when compared with benign tumors. Phospho-GSKalpha/beta (Ser9/21) staining was more intense in mitotically active carcinoma cells and exhibited a polarized localization in benign neoplasms that was absent in carcinomas. Notably, lower phospho-GSKalpha/beta (Ser9/21) immunoreactivity correlated with better survival for carcinoma patients (P=0.046). Our data are consistent with a model in which activin A may mediate ovarian oncogenesis by activating Akt and repressing GSK to stimulate cellular proliferation.


Discordance Between Perinatal Alcohol Use Among Women and Provider Counseling for Alcohol Use: An Assessment of the Pregnancy Risk Assessment Monitoring System.
In the United States, guidelines indicate all pregnant women should be screened for and counseled on alcohol use to prevent adverse perinatal outcomes due to alcohol consumption. The objective of this study was to describe sociodemographic factors associated with receipt of prenatal alcohol counseling and perinatal alcohol use among US women. State health departments collected data for the Pregnancy Risk Assessment Monitoring System Phase 7 during 2012-2015, and we restricted the sample to a complete case analysis (N = 135 111). The 3 dichotomous outcomes were preconception alcohol use (3 months before pregnancy), prenatal alcohol use (during last 3 months of pregnancy), and prenatal alcohol counseling. Predictor variables were age, race, Hispanic ethnicity, education, marital status, health insurance status, and previous live births. We estimated survey-weighted logistic regression models for each outcome. Half (56.0%) of pregnant women reported preconception alcohol use, 70.5% received prenatal alcohol counseling, and 7.7% reported prenatal alcohol use during the last 3 months of pregnancy. Black women were significantly less likely than White women (odds ratio [OR] = 0.49; 95% CI, 0.46-0.52) and Hispanic women were significantly less likely than non-Hispanic women (OR = 0.62; 95% CI, 0.58-0.66) to report preconception alcohol use. We found similar patterns for prenatal alcohol use among Black women. Black women were significantly more likely than White women (OR = 1.66; 95% CI, 1.55-1.77) and Hispanic women were significantly more likely than non-Hispanic women (OR = 1.51; 95% CI, 1.40-1.61) to receive prenatal alcohol counseling. We found similar patterns for age, education, and health insurance status. Disparities in alcohol counseling occurred despite the national recommendation for universal screening and counseling prenatally. Continued integration of universal screening for alcohol use during pregnancy is needed.


Ibuprofen modulates tetrodotoxin-resistant persistent Na+ currents at acidic pH in rat trigeminal ganglion neurons.
Non-steroidal anti-inflammatory drugs (NSAIDs) are widely used to relieve various symptoms such as headache, arthralgia, and dental pain. While the primary mechanism of NSAID-based pain relief is the inhibition of cyclooxygenase-2, several NSAIDs also modulate other molecular targets related to nociceptive transmission such as voltage-gated Na+ channels. In the present study, we examined the effects of NSAIDs on persistent Na+ current (INaP) mediated by tetrodotoxin-resistant (TTX-R) Na+ channels in small-to medium-sized trigeminal ganglion neurons using a whole-cell patch-clamp technique. At clinically relevant concentrations, all propionic acid derivatives tested (ibuprofen, naproxen, fenoprofen, and flurbiprofen) preferentially inhibited the TTX-R INaP. The inhibition was more potent at acidic extracellular pH (pH 6.5) than at normal pH (pH 7.4). Other NSAIDs, such as ketorolac, piroxicam, and aspirin, had a negligible effect on the TTX-R INaP. Ibuprofen both accelerated the onset of inactivation and retarded the recovery from inactivation of TTX-R Na+ channels at acidic extracellular pH. However, all NSAIDs tested in this study had minor effects on voltage-gated K+ currents, as well as hyperpolarization-activated and cyclic nucleotide-gated cation currents, at both acidic and normal extracellular pH. Under current-clamp conditions, ibuprofen decreased the number of action potentials elicited by depolarizing current stimuli at acidic (pH 6.5) extracellular pH. Considering that extracellular pH falls as low as 5.5 in inflamed tissues, TTX-R INaP inhibition could be a mechanism by which ibuprofen and propionic acid derivative NSAIDs modulate inflammatory pain.


Association between dietary knowledge and muscle mass in Chinese older adults: a cross-sectional and longitudinal study.
This study aims to explore the possible association between dietary knowledge and muscle mass in a Chinese population aged 60 years and above. Cross-sectional and longitudinal studies. Data from the 2006 and 2011 China Health and Nutrition Survey (CHNS) were used for this study. A total of 1487 Chinese participants (44.38% males) aged 60 and above in the 2006 survey were included in the cross-sectional study. From the same study population, a total of 1023 participants (46.82% males) with normal muscle mass on the interview date of 2006 were included in the longitudinal study. Dietary knowledge was accessed by a validated CHNS questionnaire. Appendicular skeletal muscle mass was calculated using a validated anthropometric equation derived from a representative Chinese population. Based on the 2021 Chinese consensus on sarcopenia, the appendicular skeletal muscle mass was categorised as 'normal' or 'low' using sex-specific cut-off values. The prevalence of low muscle mass in the study population was 31.20%, with a higher prevalence in females (34.22%). People with low muscle mass have a significantly lower dietary knowledge score (mean difference: -1.74, 95% CI -2.20 to -1.29). In the cross-sectional analysis, one score higher in dietary knowledge score was associated with a 4% lower odds of low muscle mass (OR=0.96, 95% CI 0.93 to 0.99). Compared with people in the lowest quartile of dietary knowledge, people in the highest quartile have a 44% lower odds of low muscle mass (OR=0.56, 95% CI 0.35 to 0.91). In the longitudinal analysis, no significant association was found between dietary knowledge and low muscle mass, yet the upper 95% CI was close to one (HR=0.97, 95% CI 0.93 to 1.01). Sufficient dietary knowledge may play a protective role in maintaining normal muscle mass in Chinese adults aged 60 or above.


[SARS: a new emergency in the world health].
The Severe Acute Respiratory Syndrome (SARS) is a new life-threatening respiratory disease which has its origins in Guangdong province, China, where the earliest known cases were identified in November 2002. Since then, probable cases of SARS have been reported in 30 countries and the current cumulative number of cases is 8,240 with 745 deaths and a global fatality rate of 9%. The most frequently involved areas include China, Hong Kong, Singapore, Canada, Vietnam and Philippines. Most cases of SARS to date have occurred in young adults and this disease appears to spread most commonly by close person-to-person contact, involving exposure to infectious droplets and body fluids. This transmission pattern generally involves household members, health care workers and international travellers, while a large and sudden cluster of almost simultaneous cases in an housing estate of Hong Kong has raised the possibility of transmission from an environmental source. The most common presenting symptoms are fever, malaise, non-productive cough and dyspnea, associated with pulmonary interstitial infiltrates on chest radiography. A novel coronavirus is associated with this outbreak, and the laboratory evidences indicate that this virus has an etiologic role in SARS, but the role of other concurrent viral agents (such as metapneumovirus) identified in these patients requires further investigation.


Angiotensin decreases cyclic GMP accumulation produced by atrial natriuretic factor.
Atrial natriuretic factor (ANF) produced rapid increases in cyclic GMP (cGMP) in cultured aortic smooth muscle cells. Angiotensin II (ANG II) markedly decreased the accumulation of cGMP that was evoked by ANF. Arginine vasopressin and ATP, which evoke transient increases in free Ca2+ similarly to ANG II, also inhibited cGMP accumulation. The effect of the calcium mobilizing neurohormones was mimicked by the divalent cation ionophore, A23187. The cyclic nucleotide phosphodiesterase inhibitor, 3-isobutyl-1-methylxanthine, prevented ANG II from inhibiting ANF-evoked cGMP accumulation. ANG II also inhibited cGMP accumulation induced by nitroprusside, a compound that activates cytosolic guanylate cyclase. These findings support the hypothesis that ANG II decreases cGMP accumulation by stimulating cGMP hydrolysis, apparently via a Ca2+-activated cGMP phosphodiesterase.


Left Atrioventricular Coupling Index to Predict Incident Heart Failure: The Multi-Ethnic Study of Atherosclerosis.
Background: Although left atrial (LA) and left ventricular (LV) structural and functional parameters have independent prognostic value as predictors of heart failure (HF), the close physiological relationship between the LA and LV suggest that the assessment of LA/LV coupling could better reflect left atrioventricular dysfunction and be a better predictor of HF. Aim: We investigated the prognostic value of a left atrioventricular coupling index (LACI), measured by cardiovascular magnetic resonance (CMR), as well as change in LACI to predict incident HF in the Multi-Ethnic Study of Atherosclerosis (MESA). Materials and Methods: In the MESA, 2,250 study participants, free of clinically recognized HF and cardiovascular disease (CVD) at baseline, had LACI assessed by CMR imaging at baseline (Exam 1, 2000-2002), and 10 years later (Exam 5, 2010-2012). Left atrioventricular coupling index was defined as the ratio of LA to LV end-diastolic volumes. Univariable and multivariable Cox proportional hazard models were used to evaluate the associations of LACI and average annualized change in LACI (ΔLACI) with incident HF after adjustment for traditional MESA-HF risk factors. The incremental risk prediction was calculated using C-statistic, categorical net reclassification index (NRI) and integrative discrimination index (IDI). Results: Among the 2,250 participants (mean age 59.3 ± 9.3 years and 47.6% male participants), 50 incident HF events occurred over 6.8 ± 1.3 years after the second CMR exam. After adjustment, greater LACI and ΔLACI were independently associated with HF (adjusted HR 1.44, 95% CI [1.25-1.66] and adjusted HR 1.55, 95% CI [1.30-1.85], respectively; both p < 0.0001). Adjusted models for LACI showed significant improvement in model discrimination and reclassification compared to currently used HF risk score model for predicting HF incidence (C-statistic: 0.81 vs. 0.77; NRI = 0.411; IDI = 0.043). After adjustment, ΔLACI showed also significant improvement in model discrimination compared to the multivariable model with traditional MESA-HF risk factors for predicting incident HF (C-statistic: 0.82 vs. 0.77; NRI = 0.491; IDI = 0.058). Conclusions: In a multi-ethnic population, atrioventricular coupling (LACI), and coupling change (ΔLACI) are independently associated with incident HF. Both have incremental prognostic value for predicting HF events over traditional HF risk factors.


[Structure of the epithelium of the parasitic turbellaria Notenera ivanovi (Turbellaria: Fecampiida)].
The ultrastructure of the epithelium in Notentera ivanovi (Turbellaria, Fecampiida) has been studied. Notentera ivanovi lacks the digestive system but has a pad of the epidermal cells on the dorsal side of the body, which seems to be similar to the digestive epidermis on LM. Both the ventral and dorsal epithelium are cellular, ciliated and not insunk (fig. 1, a). The ultrastructure of the ventral and dorsal epithelium is similar in essential features. The cells bear abundant microvilli, cilia and are very rich in mitochondria, but the cytoplasm does not contain lysosomes and shows no other indications of phago- or pinocytosis. The basal membrane of epithelial cells forms deep invaginations (fig. 1, [symbol: see text]), partly with dilations (fig. 1, a; 2, a) containing the lamellated material (3, [symbol: see text]). In the basal part of the cells the numerous Golgi apparatus and rare cysternae of the smooth endoplasmic reticulum were observed (fig. 2, a, [symbol: see text]). The epithelium consists of several types of cells, which differ in the structure of secretory granules. The most abundant type of cells contains the granules with the rough-fibrillated content (fig. 1, a; 2, [symbol: see text]; 3, a). The cells of this type cover most part of the body. In some cells the content of such granules becomes condensed and electron-dense granules appear (fig. 3, a, [symbol: see text]). Another type of cells contains the giant granules with the rough-fibrillated content (fig. 3, [symbol: see text]). Third type of the secret is the granules with the finely fibrillated content which is ejected by exocytosis. The cells of the second and third types form a separate areas of the epithelium of the dorsal side of the body but occasionally were observed in the ventral epithelium too. The epithelium of N. ivanovi differs from that in Kronborgia by the abundance and diversity of secretory contents. The role of the epithelium in the digestion remains conjectural. It seems to be mainly the suckering tissue transporting the low molecular nutrients.


Estimation of Renal Clearance in Hypertensive Rats According to fMRI Data.
Renal clearance in Wistar rats with multifactorial cardiovasorenal model of arterial hypertension was assessed by fMRI using (EPI_Diffusion_map) protocol after injection of extracellular contrast agent gadolinium Gd-DTPA. Linear regression analysis was used to assess local concentrations of the contrast agent in the abdominal aorta, kidney compartments, pelvis, and bladder areas. Detection of marker clearance in order to verify the glomerular filtration rate was performed by the RPP (Rutland-Patlak plot) method. In 3 months after hypertension modeling, glomerular filtration rate decreased by 2 times in comparison with the control (31.2±0.44 and 62.3±1.31 μl/min/100 g, respectively; p<0.001). Our findings can indicate the formation of hypertensive nephroangiosclerosis in rats with experimental arterial hypertension. It was found that kidney damage in hypertensive rats is associated with hypofiltration.


Angiogenesis: a dynamic balance of stimulators and inhibitors.
Angiogenesis, the formation of new blood vessels from a pre-existing vasculature, is tightly regulated in normal adults. Under physiological circumstances, angiogenesis occurs in only a few instances; e.g., the female reproductive system in response to ovulation or gestation, the normal hair cycle, etc. In these examples, growth of new capillaries is tightly controlled by an interplay of growth regulatory proteins which act either to stimulate or to inhibit blood vessel growth. Normally, the balance between these forces is tipped in favor of inhibition and consequently capillary growth is restrained. Under certain pathological circumstances, however, local inhibitory controls are unable to restrain the increased activity of angiogenic inducers. Thus, in wound healing, inflammation and tumors, to name just a few examples, angiogenesis is integral to the pathology, engendering the hope that these pathological entities could be regulated by pharmacological and/or genetic suppression (or enhancement) of blood vessel growth. This hope, in turn, has fostered interest in the molecular mechanisms that regulate angiogenesis. In this chapter, we have reviewed the current literature regarding some angiogenic stimulators and inhibitors, emphasizing vascular permeability factor (VPF, also known as vascular endothelial growth factor or VEGF), as a major angiogenic inducer, and thrombospondin (TSP) as the best known example of a natural inhibitor of vessel growth.


Huntingtin: here, there, everywhere!
Huntingtin is the protein mutated in Huntington disease, a dominant inherited neurodegenerative disorder. Huntingtin is ubiquitously expressed throughout the body, however its role outside the central nervous system has been overlooked. This review focuses on the peripheral distribution of huntingtin. It also highlights that huntingtin has central cellular functions, the importance of which may extend beyond the nervous system. Because of the breadth of huntingtin expression and functions, mutant huntingtin undoubtedly causes peripheral disturbances and may be involved in other non neuronal pathologies.


Recent Advances in Thiourea Based Colorimetric and Fluorescent Chemosensors for Detection of Anions and Neutral Analytes: A Review.
Thioureas and their derivatives are organosulfur compounds having excellent biological and non-biological applications. These compounds contain S- and N-, which are nucleophilic and allow for establishing inter-and intramolecular hydrogen bonding. These characteristics make thiourea moiety a very important chemosensor to detect various environmental pollutants. This article covers a broad range of thioureas and their derivatives that are used for highly sensitive, selective, and simple fluorimetric (turn-off and turn-on), and colorimetric chemosensors for the detection and determination of different types of anions, such as CN-, AcO-, F-, ClO- and citrate ions, etc., and neutral analytes such as ATP, DCP, and Amlodipine, etc., in biological, environmental, and agriculture samples. Further, the sensing performances of thioureas-based chemosensors have been compared and discussed, which could help the readers for the future design of organic fluorescent and colorimetric sensors to detect anions and neutral analytes. We hope this study will support the new thoughts to design highly efficient, selective, and sensitive chemosensors to detect different analytes in biological, environmental, and agricultural samples.


[Morphological changes and prion accumulation in the cerebellar cortex in Creutzfeldt-Jacob disease].
Histological sections of the cerebellar cortex taken from 5 patients with Creutzfeldt-Jacob disease (CJD), including 3 patients with sporadic form, were comparatively studied. The rate of pathological alterations as well as localization of prion protein (PrP) deposits greatly varied in these two groups of patients. The intensity of neural loss, damage of glial cells and accumulation of PrP increased in parallel to the duration of the disease. In nvCJD, all layers of the cerebellum, the granular layer in particular, were affected to give rise to diffuse deposits of PrP and immature amyloid plaques. Vacuolization was less pronounced and occurred predominantly in the molecular layer in all patients.


Assessment factors for extrapolation from short-time to chronic exposure--are the REACH guidelines adequate?
Due to the relative scarcity of long-term toxicity data, assessment factors for extrapolation from relatively short to chronic exposures have an important role in the risk assessment of chemicals. A recent REACH guidance document includes recommended default assessment factors that cover subacute-subchronic, subchronic-chronic, and subacute-chronic extrapolations. The recommended assessment factors are smaller than in most previous proposals, since they are calibrated to achieve central estimates (50th percentile of the target distribution) rather than a higher percentile such as the 95th, as has been more common. These assessment factors are nevertheless presented as representing a "widely agreed level of conservatism", a statement that may lead to misunderstandings of what is achieved by using them in a risk assessment. Assessment factors have been based on evidence from animal studies with different designs, in particular with focus on different endpoints. Our re-analysis of experimental data shows that using mortality as an endpoint leads to smaller assessment factors than if the factors are derived from corresponding ratios for non-lethal toxicity.


Induction, morphogenesis, and germination of the chlamydospore of Candida albicans.
Early log phase yeast cells of Candida albicans transformed into suspensor cells and chlamydospores when streaked on washed agar without added nutrients. The transformation was apparently a result of endogenous metabolism since starved yeast cells did not form chlamydospores. Addition of glucose (5 mg/ml) to washed agar completely suppressed chlamydospore formation. Size of inoculum and age of inoculum markedly affected chlamydospore yield. Electron microscopy of thin sections revealed the chlamydospore wall to be double layered, the outer thin layer being continuous with the wall of the suspensor cell. A technique was devised to study germination of chlamydospores. Chlamydospores germinated by budding, and the fluorescent antibody technique was used to study the budding process.


Eructophilia in bulimia nervosa: a clinical feature.
This report offers the first detailed description of repetitive eructation (belching) in a patient with bulimia nervosa. The case was a man in his 30's with bulimia nervosa characterized by daily bingeing and purging behavior. Detailed assessment revealed repetitive eructation which was construed as a learned behavior precipitated and maintained by aerophagia (air swallowing) secondary to regular binge-eating. Eructation was associated with a strong sense of "relief" that shared a common phenomenology with other purging behaviors. Repetitive eructation was addressed as part of outpatient treatment using a cognitive-therapy approach. Eructation became less frequent during outpatient treatment but the patient disengaged after six sessions. We define a new term "eructophilia" where repetitive eructation takes on an ego-syntonic, self-contained, and autonomous quality which serves as a reinforcing stimulus in itself. Issues of phenomenology and motivating factors are further discussed.


An In Vitro Bovine Cellular Model for Human Schlemm's Canal Endothelial Cells and Their Response to TGFβ Treatment.
Due to the limited availability of primary human Schlemm's canal (SC) endothelial cells, we aimed to develop an in vitro cellular model using the angular aqueous plexus (AAP) cells from bovine eyes. We harvested a mixture of cells from the trabecular meshwork region including AAP loops from multiple donors, followed by puromycin treatment and immunostaining of Von Willebrand factor and vascular endothelial (VE)-cadherin to confirm identity. Previously identified differentially expressed genes in glaucomatous SC cells were examined in non-glaucomatous SC cells (n = 3) under 0% or 15% equibiaxial strain for 24 hours using droplet digital polymerase chain reaction (ddPCR) and analyzed using the Ingenuity Pathway Analysis (IPA) software application to identify upstream regulators. To compare the cellular responses to candidate regulators of these mechanoresponsive genes, AAP and human SC cells (n = 3) were treated with 5 or 10 ng/mL transforming growth factor beta-2 (TGFβ2) for 24 or 48 hours, followed with expression profiling using real-time PCR or ddPCR. We found that the isolated AAP cells displayed uniform cobblestone-like morphology and positive expression of two endothelial markers. In stretched SC cells, nine glaucoma-related genes were upregulated, and IPA implicated TGFβ as a potential upstream regulator. The effects of TGFβ2 treatment were similar for both AAP and SC cells in a dose- and time-dependent manner, activating TGFBR1 and SMAD2, inhibiting BMP4, and altering expression of three glaucoma-related genes (DCN,EZR, and CYP1B1). Bovine AAP cells may serve as an alternative cellular model of human SC cells. These AAP cells may be used to study the functional pathways related to the outflow facility.


Subtypes of Epstein-Barr virus in human immunodeficiency virus-associated non-Hodgkin lymphoma.
Biopsy samples obtained from 20 patients with human immunodeficiency virus (HIV)-associated non-Hodgkin lymphoma (NHL) were assessed for evidence of Epstein-Barr virus (EBV) and HIV sequences. DNA was extracted from formalin-fixed, paraffin-embedded NHL tissue and specific viral gene sequences were sought using the polymerase chain reaction (PCR). EBV sequences were found in 10 NHL samples (50%), with five tumors showing A-type and five B-type sequences. By serologic testing, 18 of 19 patients had antibodies to EBV, with 14 patients having antibodies to A-type EBV and 11 to B-type EBV. Serology confirmed the high prevalence of type B EBV in HIV-infected patients, but was not a reliable indicator of the EBV subtype present in the lymphomas. HIV sequences were present in biopsy tissue but at a level consistent with an origin from bystander HIV-infected cells. All 20 patients were negative by enzyme-linked immunosorbent assay for antibodies to human T-cell leukemia virus-type I. The high prevalence of type B EBV in these tumors is similar to the findings in endemic Burkitt's lymphoma, where 40% of the tumors have type B viral sequences. In normal populations, type B EBV is rarely found outside the nasopharynx. These studies support the hypothesis that EBV is an important cofactor in NHL in HIV-infected persons. The finding that B-type EBV is present in 25% of HIV-associated NHL suggests that this EBV subtype may be an important human pathogen with a wider geographic distribution than originally thought.


Comparative Analysis of PFOS and PFOA Toxicity on Sertoli Cells.
Perfluoroalkyl chemicals induce male reproductive toxicity. Current evidence showed the effects of the chemical exposure on the deterioration of testicular functions, and reduction in epididymal sperm counts. Previous studies showed that PFOA and PFOS displayed a high correlation with each other in seminal plasma levels, but induced different effects on semen variables. In this study, we focused on the comparative toxicity analysis of PFOA and PFOS, using a rat primary Sertoli cell model. Our transcriptomic data showed that PFOA and PFOS treatments (40 μM) perturbed global gene expression. While PFOS induced higher toxicity in affecting cytoskeleton signaling, Sertoli cell-cell junction, and inflammation, underlined by Ingenuity pathway analysis. Immunocytochemical staining revealed that PFOS treatment (40 and 80 μM) induced truncated actin filament and disorganized bundled configuration in the cell cytoplasm. Moreover, disorganized distribution of N-cadherin (N-cad) and β-catenin (β-cat), and defragmentation of ZO-1 at the Sertoli cell-cell interface was evident. At 80 μM of PFOS, cytoplasmic distribution of N-cad, β-cat, and ZO-1 were observed. We then examined whether resveratrol, a polyphenol antioxidant, was able to protect the cells from PFOS toxicity. The pretreatment of Sertoli cells with 10 μM resveratrol prevented the formation of truncated actin filament and dis-localization of β-cat. Western blot analysis showed that Res pretreatment increased the levels of basal ES proteins (N-cad and β-cat), tight junction proteins (ZO-1 and occludin), and gap junction protein, versus control.


Magnetic iron oxide-fluorescent carbon dots integrated nanoparticles for dual-modal imaging, near-infrared light-responsive drug carrier and photothermal therapy.
Multifunctional hybrid nanoparticles (NPs, ∼100 nm) that combine magnetic Fe3O4 nanocrystals and fluorescent carbon dots (CDs) in porous carbon (C) were successfully synthesized using a one-pot solvothermal method by simply increasing the H2O2 concentration. The resultant Fe3O4@C-CDs hybrid NPs not only demonstrate excellent magnetic responsive properties (Ms = 32.5 emu g-1) and magnetic resonance imaging ability (r = 674.4 mM-1 s-1) from the Fe3O4 nanocrystal core, but also exhibit intriguing photoluminescent (quantum yield ∼6.8%) properties including upconversion fluorescence and excellent photostability from the CDs produced in the porous carbon. The hybrid NPs can enter the intracellular region and illuminate mouse melanoma B16F10 cells under different excitation wavelengths. Meanwhile, the mesoporous carbon shell and hydrophilic surface functional groups endow the hybrid NPs with high loading capacity (835 mg g-1) for the anti-cancer drug doxorubicin and excellent stability in aqueous solutions. More importantly, the hybrid NPs can absorb and convert near-infrared (NIR) light to heat due to the existence of CDs, and thus, can realise NIR-controlled drug release and combined photothermo/chemotherapy for high therapeutic efficacy. Such nanostructured Fe3O4@C-CDs hybrid NPs demonstrate great promise towards advanced nanoplatforms for simultaneous imaging diagnostics and high efficacy therapy.


Reliability and validity of young adults' anonymous online reports of marijuana use and thoughts about use.
With growing interest in online assessment of substance abuse behaviors, there is a need to formally evaluate the validity of the data gathered. The current investigation evaluated the reliability and validity of anonymous, online reports of young adults' marijuana use and related cognitions. Young adults age 18 to 25 who had smoked at least one cigarette in the past 30 days were recruited over 14 months to complete an anonymous online survey. Of 3,106 eligible cases, 1,617 (52%) completed the entire survey. Of those, 54% (n = 884) reported past-month marijuana use (65% male, 70% Caucasian, mean age was 20.4 years [SD = 2.0]). Prevalence of marijuana use was reported reliably across three similar items, and interitem correlations ranged from fair to excellent for measures of marijuana dependence symptoms and thoughts about marijuana use. Marijuana use frequency demonstrated good construct validity through expected correlations with marijuana use constructs, and nonsignificant correlations with thoughts about tobacco use. Marijuana frequency distinguished among stages of change for marijuana use and goals for use, but not among gender, ethnicity, or employment groups. Marijuana use and thoughts about use differed by stage of change in the hypothesized directions. Self-reported marijuana use and associated cognitions reported anonymously online from young adults are generally reliable and valid. Online assessments of substance use broaden the reach of addictions research.


Recovery of visual functions after early acquired occipital damage.
Plasticity of visual systems after early brain damage has been extensively studied in animal models but poorly documented in children after visual pathway lesions. This report describes the visual recovery of a male child who had a bilateral occipital lobe infarction at the age of 2 years 6 months, 10 days after colon resection for Hirschsprung disease. In the acute phase he had severe visual impairment without visual response. Some weeks later he could perceive movement. Since then, progressive recovery of his visual acuity and oculomotor abilities has been accompanied by a progressive reduction of the visual field defect. At 6 years 8 months, visual recognition acuity was 10/10 in both eyes and neuro-ophthalmological examination was normal, except for persistence of the visual field defect in the upper hemifield and a selective impairment of higher visual functions (recognition of object presented in a hard-to-decode way [e.g. overlapping figures], or use of complex visuospatial skills). The functional recovery observed in this patient confirms the adaptive plasticity of developing visual systems after early brain lesions. It suggests that in humans, as in animal models, processes related to cerebral plasticity may take place years after a brain lesion has been sustained.


Accelerated estimation and permutation inference for ACE modeling.
There are a wealth of tools for fitting linear models at each location in the brain in neuroimaging analysis, and a wealth of genetic tools for estimating heritability for a small number of phenotypes. But there remains a need for computationally efficient neuroimaging genetic tools that can conduct analyses at the brain-wide scale. Here we present a simple method for heritability estimation on twins that replaces a variance component model-which requires iterative optimisation-with a (noniterative) linear regression model, by transforming data to squared twin-pair differences. We demonstrate that the method has comparable bias, mean squared error, false positive risk, and power to best practice maximum-likelihood-based methods, while requiring a small fraction of the computation time. Combined with permutation, we call this approach "Accelerated Permutation Inference for the ACE Model (APACE)" where ACE refers to the additive genetic (A) effects, and common (C), and unique (E) environmental influences on the trait. We show how the use of spatial statistics like cluster size can dramatically improve power, and illustrate the method on a heritability analysis of an fMRI working memory dataset.


Nonsteroidal anti-inflammatory drugs and peroxisome proliferator-activated receptor-gamma agonists modulate immunostimulated processing of amyloid precursor protein through regulation of beta-secretase.
Long-term treatment with nonsteroidal anti-inflammatory drugs (NSAIDs) reduces the risk for Alzheimer's disease (AD). To determine the mechanisms by which inflammation affects AD and how NSAIDs protect against it, we stimulated neuroblastoma cells stably transfected with amyloid precursor protein (APP) with proinflammatory cytokines, which increased the secretion of amyloid-beta and APP ectodomain. Addition of ibuprofen, indomethacin, peroxisome proliferator-activated receptor-gamma (PPARgamma) agonists, or cotransfection with PPARgamma cDNA reversed this effect. The inhibitory action of ibuprofen and indomethacin was suppressed by PPARgamma antagonists. Finally, we observed that the mRNA levels, expression, and enzymatic activity of beta-secretase were increased by immunostimulation and normalized by NSAIDs. In conclusion, proinflammatory cytokines activate beta-secretase, and NSAIDs inhibit this effect through PPARgamma.


Plasma neutrophil gelatinase-associated lipocalin and worsening renal function during everolimus therapy after heart transplantation.
Recently, the mammalian target of rapamycin inhibitor everolimus (EVL) has been introduced as a novel immunosuppressant for heart transplant (HTx) recipients, and is expected to preserve renal function compared to conventional calcineurin inhibitors (CNIs). However, a considerable number of recipients treated with EVL were not free from worsening renal function regardless of CNI reduction. Data were collected retrospectively from 27 HTx recipients who had received EVL (trough concentration, 3.1-9.2 ng/mL) along with reduced CNIs (%decreases in trough concentration, 27.3 ± 13.0%) because of switching from mycophenolate mophetil due to digestive symptoms or neutropenia, progressive coronary artery vasculopathy, or persistent renal dysfunction, and had been followed over 1 year between August 2008 and January 2013. Estimated glomerular filtration rate (eGFR) decreased in 5 recipients (18.5%) during the study period. Univariate logistic regression analysis demonstrated that a higher plasma neutrophil gelatinase-associated lipocalin (P-NGAL) level was the only significant predictor for a decrease in eGFR over a 1-year EVL treatment period among all baseline parameters (P = 0.008). eGFR and proteinuria worsened almost exclusively in patients with baseline P-NGAL ≥ 85 ng/mL, which was the cutoff value calculated by an ROC analysis (area under the curve, 0.955; sensitivity, 1.000; specificity, 0.955). In conclusion, higher P-NGAL may be a novel predictor for the worsening of renal function after EVL treatment that is resistant to CNI reduction in HTx recipients.


A comparison of the practice patterns of emergency department teams that include physicians, nurse practitioners, or physician assistants.
Physicians see most emergency department (ED) patients, but, recently, nurse practitioners (NPs) and physician assistants (PAs) have provided an increasing amount of ED care. Compare NP and PA teams' practice patterns to physician teams in EDs. Using 12 years of data from the National Hospital Ambulatory Medical Care Survey (2009-2020), we used multivariate regression analysis to separately examine the associations between the ED practice patterns (i.e., number of diagnostic services, number of procedures, waiting time, boarding time, length of visit, and hospital admission) of patients seen by NP or PA teams compared with physician teams. Patient visits to NP and PA teams received fewer diagnostic services and procedures, had shorter visits, and were less likely to be hospitalized. If the additional diagnostic services, procedures, and hospital admission provided by physician teams were unnecessary for the patients studied, NP and PA team care could be more efficient.


Autosomal and uniparental portraits of the native populations of Sakha (Yakutia): implications for the peopling of Northeast Eurasia.
Sakha--an area connecting South and Northeast Siberia--is significant for understanding the history of peopling of Northeast Eurasia and the Americas. Previous studies have shown a genetic contiguity between Siberia and East Asia and the key role of South Siberia in the colonization of Siberia. We report the results of a high-resolution phylogenetic analysis of 701 mtDNAs and 318 Y chromosomes from five native populations of Sakha (Yakuts, Evenks, Evens, Yukaghirs and Dolgans) and of the analysis of more than 500,000 autosomal SNPs of 758 individuals from 55 populations, including 40 previously unpublished samples from Siberia. Phylogenetically terminal clades of East Asian mtDNA haplogroups C and D and Y-chromosome haplogroups N1c, N1b and C3, constituting the core of the gene pool of the native populations from Sakha, connect Sakha and South Siberia. Analysis of autosomal SNP data confirms the genetic continuity between Sakha and South Siberia. Maternal lineages D5a2a2, C4a1c, C4a2, C5b1b and the Yakut-specific STR sub-clade of Y-chromosome haplogroup N1c can be linked to a migration of Yakut ancestors, while the paternal lineage C3c was most likely carried to Sakha by the expansion of the Tungusic people. MtDNA haplogroups Z1a1b and Z1a3, present in Yukaghirs, Evens and Dolgans, show traces of different and probably more ancient migration(s). Analysis of both haploid loci and autosomal SNP data revealed only minor genetic components shared between Sakha and the extreme Northeast Siberia. Although the major part of West Eurasian maternal and paternal lineages in Sakha could originate from recent admixture with East Europeans, mtDNA haplogroups H8, H20a and HV1a1a, as well as Y-chromosome haplogroup J, more probably reflect an ancient gene flow from West Eurasia through Central Asia and South Siberia. Our high-resolution phylogenetic dissection of mtDNA and Y-chromosome haplogroups as well as analysis of autosomal SNP data suggests that Sakha was colonized by repeated expansions from South Siberia with minor gene flow from the Lower Amur/Southern Okhotsk region and/or Kamchatka. The minor West Eurasian component in Sakha attests to both recent and ongoing admixture with East Europeans and an ancient gene flow from West Eurasia.


Microwave drying of fish, chicken and beef samples.
In this study, the drying characteristics of fish, chicken and beef samples were investigated using microwave drying method. Each sample was dried using four different microwave powers of 90, 180, 270 and 360 W. Drying time decreased as microwave power increased. Fish fillets were dried in a shorter time than chicken and beef samples. The experimentally obtained data were fitted to seven drying models. The logarithmic and Midilli et al. models were found to be the most appropriate in describing microwave drying behavior of meat samples. Effective moisture diffusion coefficients were computed and found between 1.74 × 10-7 and 16.4 × 10-7 m2 s-1 for all the meat samples. The activation energies were found as 14.59 W/g, 79.147 W/g and 140.81 W/g, for chicken, fish and beef meat samples, respectively. The highest and lowest energy consumptions were found in the chicken drying process at 90 W (0.045 kWh) and fish drying process at 360 W (0.018 kWh), respectively. The microwave power level are the main factors affecting the color change of material during drying process, where the highest and the lowest ΔE is obtained t chicken and fish samples, respectively.


Lack of interaction between a hypertonic NaCl stimulus and the brain renin-angiotensin system.
Sodium and the renin-angiotensin system (RAS) participate in the regulation of cardiovascular function, in part via activation of central nervous system (CNS) mechanisms. Because intraventricular (IVT) administration of either hypertonic sodium chloride (NaCl) or angiotensin II (ANG II) elicits similar effects (i.e., natriuresis, hypertension, increased drinking, and enhanced vasopressin release) a common and final pathway may be involved. With this in mind, we measured the effect of an IVT injection (third or lateral ventricle) of 0.6 M NaCl on postganglionic renal nerve activity (RNA) and blood pressure in morphine-pentobarbital-anesthetized dogs before and after blockade of the brain RAS with either captopril or [Sar1,Ile8]ANG II. Both vagus and carotid sinus nerves were cut to avoid impingement of the baroreceptor reflex on the measured variables. IVT injection of 0.6 M NaCl produced a prominent hypertensive response and tachycardia associated with a 59 +/- 9% increase in RNA. These changes were statistically significant (P less than 0.001), correlated with each other, and were abolished by administration of hexamethonium chloride (10 mg/kg iv). Blockade of central ANG II receptors with [Sar1,Ile8]ANG II was without effect. However, in dogs given IVT SQ 14,225, there was a slight increase in baseline RNA before injection of 0.6 M NaCl; in addition, both the pressor and heart rate responses to the stimulus of hypertonic NaCl were further augmented. These results demonstrate that central administration of hypertonic NaCl in baroreceptor-denervated dogs produces marked activation of sympathetic nerve activity via mechanisms other than activation of the brain RAS.


In Search of a Phosphorus Dendrimer-Based Carrier of Rose Bengal: Tyramine Linker Limits Fluorescent and Phototoxic Properties of a Photosensitizer.
Photodynamic therapy (PDT) is a skin cancer treatment alternative to chemotherapy and radiotherapy. This method exploits three elements: a phototoxic compound (photosensitizer), light source and oxygen. Upon irradiation by light of a specific wavelength, the photosensitizer generates reactive oxygen species triggering the cascade of reactions leading to cell death. The positive therapeutic effect of PDT may be limited due to low solubility, low tumor specificity and inefficient cellular uptake of photosensitizers. A promising approach to overcome these obstacles involves the use of nanocarrier systems. The aim of this initial study was to determine the potential of the application of phosphorus dendrimers as carriers of a photosensitizer-rose bengal (RB). The primary goal involved the synthesis and in vitro studies of covalent drug-dendrimer conjugates. Our approach allowed us to obtain RB-dendrimer conjugates with the use of tyramine as an aromatic linker between the carrier and the drug. The compounds were characterized by FT-IR, 1H NMR, 13C NMR, 31P NMR, size and zeta potential measurements and spectrofluorimetric analysis. The dialysis to check the drug release from the conjugate, flow cytometry to specify intracellular uptake, and singlet oxygen generation assay were also applied. Finally, we used MTT assay to determine the biological activity of the tested compounds. The results of our experiments indicate that the conjugation of RB to phosphorus dendrimers via the tyramine linker decreases photodynamic activity of RB.


The impact of machine learning techniques in the study of bipolar disorder: A systematic review.
Machine learning techniques provide new methods to predict diagnosis and clinical outcomes at an individual level. We aim to review the existing literature on the use of machine learning techniques in the assessment of subjects with bipolar disorder. We systematically searched PubMed, Embase and Web of Science for articles published in any language up to January 2017. We found 757 abstracts and included 51 studies in our review. Most of the included studies used multiple levels of biological data to distinguish the diagnosis of bipolar disorder from other psychiatric disorders or healthy controls. We also found studies that assessed the prediction of clinical outcomes and studies using unsupervised machine learning to build more consistent clinical phenotypes of bipolar disorder. We concluded that given the clinical heterogeneity of samples of patients with BD, machine learning techniques may provide clinicians and researchers with important insights in fields such as diagnosis, personalized treatment and prognosis orientation.