Electrical impedance tomography with an optimized calculable square sensor.
Electrical impedance tomography is a technique that reconstructs the medium distribution in a region of interest through electrical measurements on its boundary. In this paper, an optimized square sensor was designed for electrical impedance tomography in order to obtain maximum information over the cross section of interest, e.g., circulating fluidized beds, in the sense of Shannon information entropy. An analytical model of the sensor was obtained using the conformal transformation. The model indicates that the square sensor possesses calculable property, which allows the calculation of standard values of the sensor directly from a single dimensional measurement that can be made traceable to the SI unit of length. Based on the model, the sensitivity maps and electrical field lines can be calculated in less than a second. Two model based algorithms for image reconstruction, i.e., back projection algorithm based on electrical field lines and iterative Lavrentiev regularization algorithm based on the sensitivity map, were introduced. Simulated results and experimental results validate the feasibility of the algorithms.


Differing strategies for sudden death prevention in hypertrophic cardiomyopathy.
Sudden death (SD) has traditionally been the most visible and feared complication of hypertrophic cardiomyopathy (HCM). Substantial progress in reducing the occurrence of these catastrophic events represents a new paradigm in disease management. Prevention of SD in HCM has resulted from introduction of primary prevention ICDs that reliably terminate life-threatening ventricular tachyarrhythmias, as well as a matured risk stratification algorithm capable of reliably identifying those patients at highest risk. This initiative has been a major determinant of reducing HCM-related mortality to a low rate of 0.5%/year. In such a heterogeneous heart disease as HCM, no perfect risk stratification strategy is possible, and available approaches differ in terms of sensitivity and specificity for identifying patients with SD risk. Major cardiovascular societies, American Heart Association/American College of Cardiology in the USA and European Society of Cardiology in Europe have promoted different risk stratification guidelines creating the potential for judging SD risk in a given HCM patient differently based on commitment to a particular societal guideline or country of residence. In this review, we provide a critical but balanced assessment of these two divergent SD prevention strategies with regard to their respective strengths and weaknesses, as a guide to clinicians directly engaged in this important management issue.


The effects of soybean storage under controlled atmosphere at different temperatures on lipid oxidation and volatile compounds profile.
This study aimed to evaluate the effects of low oxygen partial pressure (pO2) and high carbon dioxide partial pressure (pCO2) combined with different temperatures on the oil acidity and peroxide values of two soybean cultivars (NA 5909 RG and FEPAGRO 37 RR). The volatile compounds correlated to lipid oxidation were also evaluated. Soybeans were stored for seven months under ambient and controlled atmosphere (CA) conditions at three temperatures (20, 25, and 30 °C). Storage under ambient conditions increased acidity and peroxide value regardless of the temperature. CA storage with low pO2 reduced oil acidity and its combination with high pCO2 had no positive effects on oil acidity and peroxide values. Grains of FEPAGRO 37 RR stored under ambient air showed higher 1-octne-3-ol amount compared to CA. The higher storage temperature increased (E)-2-heptenal and decanal amount in grains of cultivar NA 5909 RG. In addition, the ambiente air storage provide higher γ-Butyrolactone in relation to CA storage. Moreover, in both cultivars the CA storage technique provides lower (E)-2-hexenal content. This compound, together with hexanal are potential lipid deterioration markers of soybeans. CA storage is a promising tool for soybean grains preservation and the effect is mainly due to the oxygen reduction, with no additional effect of CO2 increasing.


The influence of exposure approaches to in vitro lung epithelial barrier models to assess engineered nanomaterial hazard.
Exposure to engineered nanomaterials (ENM) poses a potential health risk to humans through long-term, repetitive low-dose exposures. Currently, this is not commonplace within in vitro lung cell cultures. Therefore, the purpose of this study was to consider the optimal exposure approach toward determining the stability, sensitivity and validity of using in vitro lung cell mono- and co-cultures to determine ENM hazard. A range of exposure scenarios were conducted with DQ12 (previously established as a positive particle control) (historic and re-activated), TiO2 (JRC NM-105) and BaSO4 (JRC NM-220) on both monocultures of A549 cells as well as co-cultures of A549 cells and differentiated THP-1 cells. Cell cultures were exposed to either a single, or a repeated exposure over 24, 48- or 72-hours at in vivo extrapolated concentrations of 0-5.2 µg/cm2, 0-6 µg/cm2 and 0-1µg/cm2. The focus of this study was the pro-inflammatory, cytotoxic and genotoxic response elicited by these ENMs. Exposure to DQ12 caused pro-inflammatory responses after 48 hours repeat exposures, as well as increases in micronucleus frequency. Neither TiO2 nor BaSO4 elicited a pro-inflammatory response at this time point. However, there was induction of IL-6 after 24 hours TiO2 exposure. In conclusion, it is important to consider the appropriateness of the positive control implemented, the cell culture model, the time of exposure as well as the type of exposure (bolus or fractionated) before establishing if an in vitro model is appropriate to determine the level of response to the specific ENM of interest.


[Pathogenicity of Spiroplasma sabaudiense (mollicute) for the cells (c6/36) of Aedes albopictus (Insecta: Diptera) in vitro].
An initial stock of Spiroplasma sabaudiense had been maintained in cell-free medium for 2-3 years. Subsequent passages in Leibovitz's medium L-15 in the presence of Aedes albopictus (C6/36) cells dramatically increased the pathogenicity of S. sabaudiense towards these cells. Cytopathogenicity included production of syncytia, an increase in the number of mitochondria and alteration of their morphology, vacuolisation and a reduction in the rate of growth. Cell lysis was associated with cytadsorption by spiroplasmas and was apparent following the third passage. At six days post-inoculation during the fourth and fifth passages, cell cultures had been totally destroyed by S. sabaudiense. The intra-cellular stage of S. sabaudiense is described and the literature pertaining to the pathogenicity of spiroplasmas for insects is reviewed.


The role of platelets in antiphospholipid syndrome.
Despite extensive research, the pathogenesis of antiphospholipid syndrome (APS) remains obscure in many aspects. However, it is widely accepted that thrombosis is the result of a hypercoagulable state caused by antibodies directed against β2-glycoprotein I (β2-GPI), a protein whose physiological role is unknown. Although underestimated, platelets may be involved in APS and its thrombotic manifestations, especially arterial, in several ways. Thrombocytopenia is the most relevant non-criteria manifestation of APS, possibly caused by direct binding of anti-β2-GPI antibodies or anti-β2-GPI-β2-GPI complexes. On the other hand, platelets may have a key role in APS-related thrombosis due to the presence of multiple receptors that can interact with anti-β2-GPI antibodies (especially apolipoprotein E receptor 2' (apoER2') and glycoprotein Ibα (GPIbα)) with consequent release of different procoagulant mediators such as thromboxane B2, platelet factor 4 (PF4), and platelet factor 4 variant (CXCL4L1). The aim of this review is to put together evidence on the possible role of platelets in APS and to stimulate further research on the issue.


Physiological, Perceptual, and Affective Responses to Six High-Intensity Interval Training Protocols.
This study examined the extent to which different high-intensity interval training (HIIT) and sprint interval training (SIT) protocols could influence psychophysiological responses in moderately active young men. Fourteen participants completed, in a randomized order, three cycling protocols (SIT: 4 × 30-second all-out sprints; Tabata: 7 × 20 seconds at 170% ⋮O2max; and HIIT: 10 × 60 seconds at 90% HRmax) and three running HIIT protocols (4 × 4 minutes at 90%-95% HRmax, 5 × at v⋮O2max, and 4 × 1,000 meters at a rating of perceived exertion (RPE) of 8, from the OMNI-Walk/Run scale). Oxygen uptake (⋮O2), heart rate, and RPE were recorded during each interval. Affective responses were assessed before and after each trial. The Tabata protocol elicited the highest ⋮O2 and RPE responses, and the least pleasant session-affect among the cycling trials. The v⋮O2max elicited the highest ⋮O2 and RPE responses and the lowest mean session-affect among the running trials. Findings highlight the limited application of SIT and some HIIT protocols to individuals with low fitness levels.


The IASLC Lung Cancer Staging Project: Proposals for the Revision of the N Descriptors in the Forthcoming 9th Edition of the TNM Classification for Lung Cancer.
The accurate assessment of nodal (N) status is crucial to the management and prognostication of non-metastatic non-small cell lung cancer. We sought to determine whether the current N descriptors should be maintained or revised for the upcoming 9th edition of the international Tumor Node Metastasis (TNM) lung cancer staging system. Data was assembled by the International Association for the Study of Lung Cancer on patients with non-small cell lung cancer, detailing both clinical and pathologic N status, with information about anatomic location and individual station-level identification. Survival was calculated by the Kaplan-Meier method and prognostic groups were assessed by a Cox regression analysis. Data for clinical N and pathologic N status were available in 45,032 and 35,009 patients, respectively. The current N0 to N3 descriptors for both clinical N and pathologic N categories demonstrated prognostically distinct groups. Furthermore, single station N2 involvement (N2a) demonstrated better prognosis than multistation N2 involvement (N2b) in both clinical and pathologic classifications, and the differences between all neighboring nodal subcategories were highly significant. The prognostic differences between N2a and N2b were robust and consistent across resection status, histologic type, T category, and geographic region. The current N descriptors should be maintained, with the addition of new sub-descriptors to N2 for single station involvement (N2a) and multiple station involvement (N2b).


Deformation of a self-propelled domain in an excitable reaction-diffusion system.
We formulate a theory for a self-propelled domain in an excitable reaction-diffusion system in two dimensions where the domain deforms from a circular shape when the propagation velocity is increased. In the singular limit where the width of the domain boundary is infinitesimally thin, we derive a set of equations of motion for the center of gravity and two fundamental deformation modes. The deformed shapes of a steadily propagating domain are obtained. The set of time-evolution equations exhibits a bifurcation from a straight motion to a circular motion by changing the system parameters.


Effect of orientation on the physical properties of potato amylose and high-amylose corn starch films.
The effect of orientation on the properties of amylose and starch films was studied in order to determine if film strength, flexibility, and water resistance could be improved. Potato amylose and high (70%) amylose corn starch were peracetylated, cast into films, stretched in hot glycerol 1-6 times the original length, and deacetylated. Molecular orientation of potato amylose films was much higher than for high-amylose corn starch films as determined by optical birefringence. For potato amylose films, orientation resulted in large increases in tensile strength and elongation but little change in modulus. For high-amylose corn starch films, tensile strength and modulus did not change with draw ratio but elongation to break increased from about 8% to 27% as draw ratio increased from 1 to 5. Scanning electron micrographs revealed many small crazes in the drawn starch films, suggesting that the improved film toughness was due to energy dissipation during deformation of the crazes. Annealing of drawn films at 100% humidity resulted in partial crystallization and improved wet strength.


In vivo measurement of the mouse pulmonary endothelial surface layer.
The endothelial glycocalyx is a layer of proteoglycans and associated glycosaminoglycans lining the vascular lumen. In vivo, the glycocalyx is highly hydrated, forming a substantial endothelial surface layer (ESL) that contributes to the maintenance of endothelial function. As the endothelial glycocalyx is often aberrant in vitro and is lost during standard tissue fixation techniques, study of the ESL requires use of intravital microscopy. To best approximate the complex physiology of the alveolar microvasculature, pulmonary intravital imaging is ideally performed on a freely-moving lung. These preparations, however, typically suffer from extensive motion artifact. We demonstrate how closed-chest intravital microscopy of a freely-moving mouse lung can be used to measure glycocalyx integrity via ESL exclusion of fluorescently-labeled high molecular weight dextrans from the endothelial surface. This non-recovery surgical technique, which requires simultaneous brightfield and fluorescent imaging of the mouse lung, allows for longitudinal observation of the subpleural microvasculature without evidence of inducing confounding lung injury.


The relationship between workplace environment and employee health behaviors in a South African workforce.
To determine the relationship between the availability of wellness facilities at worksites and self-reported employee health behaviors (physical activity [PA] and nutrition [NUT]). Employers (n = 71) and employees (n = 11472) participated in the South African Healthy Company Index survey. The survey included self-reported clinical measures and lifestyle behaviors. A facility score was calculated, ranging from 0 to 100. Hierarchical linear models were used to calculate the relationship between facility scores and whether employees met PA and NUT guidelines. The mean total facility score was 58.5 ± 25.5. The number of facilities at each worksite accounted for 5.4% of the variance in PA among employees (r = 0.054; P = 0.036). Higher facility scores were associated with better NUT habits among employees. Employers providing wellness facilities are likely to have employees with better PA and NUT habits.


Diagnosis and surgical treatment of pancreatic endocrine tumors in 36 patients: a single-center report.
Pancreatic endocrine tumors (PETs) are rare and their surgical treatment is often debated. The purpose of this retrospective study was to analyze the diagnosis and surgical strategy of functioning and non-functioning PETs. From May 1980 to March 2006, 36 patients with pancreatic endocrine tumors at the Second Affiliated Hospital of Zhejiang University were retrospectively studied. Among the 36 patients, 29 (81%) had functioning tumors, and 7 (19%) had nonfunctioning tumors. Ninety-two percent of insulinomas were benign, whereas 4 (57%) of nonfunctioning PETs were malignant. The size of functioning tumors was (2.3 +/- 0.3) cm, that of nonfunctioning tumors was less than (5.1 +/- 0.5) cm. The combination CT and transabdominal ultrasonography resulted in a diagnostic sensitivity of 84%. Thirty-three primary lesions were precisely located in 32 patients (89%). Atypical tumor resection was performed for 73% of functioning tumors, while typical pancreatectomy was performed for 6 (85%) of nonfunctioning tumors. Moreover, 5 liver resections and 1 lymph node dissection were performed. During the follow-up, fifteen complications occurred in 12 (36%) patients after operation. The 5-year survival rate for patients with benign tumors was 92% compared to 50% for those with malignant tumors. Surgical cure was achieved in 95% of patients with benign insulinomas. Surgical strategy for PETs depends on the size and location of the tumor and the risk of malignancy. The optimal surgical procedure is key to prevent postoperative complication. Radical resection including initial and metastatic lesion may benefit patients with malignant PETs.


Extremely Low Density and Super-Compressible Graphene Cellular Materials.
Development of extremely low density graphene elastomer (GE) holds the potential to enable new properties that traditional cellular materials cannot offer, which are promising for a range of emerging applications, ranging from flexible electronics to multifunctional scaffolds. However, existing graphene foams with extremely low density are generally found to have very poor mechanical resilience. It is scientifically intriguing but remains unresolved whether and how the density limit of this class of cellular materials can be further pushed down while their mechanical resilience is being retained. In this work, a simple annealing strategy is developed to investigate the role of intersheet interactions in the formation of extreme-low-density of graphene-based cellular materials. It is discovered that the density limit of mechanically resilient cellular GEs can be further pushed down as low as 0.16 mg cm-3 through thermal annealing. The resultant extremely low density GEs reveal a range of unprecedented properties, including complete recovery from 98% compression in both of liquid and air, ultrahigh solvent adsorption capacity, ultrahigh pressure sensitivity, and light transmittance.


Spatial structure of forest lepidopteran communities in oak hickory forests of Indiana.
The response of forest insect communities to disturbances such as timber harvest will likely depend on the underlying spatial structure of species assemblages before the disturbance occurs. Unfortunately, many studies of forest management implicitly assume homogeneity of community structure before harvest; postlogging communities are inferred to be a direct product of the imposed management. The goal of this study is to examine variation in the community structure of forest Lepidoptera using the pretimber harvest data on Lepidoptera from 20 forest sites within three watersheds at Morgan Monroe State Forest, IN. A total of 14,537 individuals representing 324 species of Lepidoptera were sampled from Morgan-Monroe State Forest in 2007. Sampling efficiency was not a function of management unit, and, surprisingly, we found little evidence that management units differed in overall community composition. Diversity partitioning suggested that > 99% of Simpson diversity (species dominance) was determined at the local scale, and each site contained the same 10 dominant taxa in rank order. Variation in species richness seemed to be more a problem of sampling bias than underlying differences in habitat preference by moth feeding guilds. Finally, Mantel tests suggested that forest moth communities at Morgan-Monroe are not spatially autocorrelated. The results here are encouraging because they strongly suggest that shifts in lepidopteran community structure should reflect the community response to disturbance rather than inherent spatial heterogeneity of species composition.


Multicenter evaluation of maprotiline hydrochloride for treatment of depression.
Maprotiline hydrochloride tablets were given to 266 patients with either a dysthymic disorder or a major depressive disorder. The mean starting dosage was 70.2 mg/day in patients younger than 60 years of age and 68.6 mg/day in those aged 60 years and over. For patients completing at least four weeks of treatment, the mean final dosage was 127.6 mg/day in younger patients and 100.0 mg/day in geriatric patients. Follow-up evaluations of response and adverse effects were made at each of the following intervals after the start of therapy: one week, two to three weeks, four to five weeks, and six weeks or more. Assessment of response was based on the physicians' evaluations of overall improvement and improvement in sleep pattern, anxiety level, mood, and drive. Eighteen patients never returned and were excluded from all assessments. The remaining patients were evaluated for observations recorded within the foregoing time intervals. A rapid onset of action was evident in the fact that 73% of evaluated patients had at least a minimal response after one week of treatment, and after six weeks 76% had achieved moderate or marked improvement in their overall condition. Patients' sleeping patterns showed the most rapid and dramatic response, with 59% of evaluated patients improved after one week and 90% after six weeks of maprotiline. Anxiety decreased in 57% of patients after one week and in 81% after six weeks. Depression was reduced in 46% of evaluated patients after one week and in 86% after six weeks. Forty-one percent of patients exhibited more drive after one week of maprotiline and 78% did so after six weeks.(ABSTRACT TRUNCATED AT 250 WORDS)


Assessing the Stability of Aortic Aneurysms with Pulse Wave Imaging.
Purpose To assess whether the stability of murine aortic aneurysms is associated with the homogeneity of pulse wave propagation within the saccular wall. Materials and Methods All animal procedures were approved by the institutional Animal Care and Use Committee. Apolipoprotein E and tissue inhibitor of metalloproteinases-1 knockout mice (n = 26) were infused with angiotensin II by using subcutaneously implanted osmotic pumps, with an additional control mouse used for histologic examination (n = 1). Pulse wave imaging (PWI) was performed just before infusion and 15 days after infusion by using 40-MHz ultrasonography at 8000 frames per second (with electrocardiographic gating). Aneurysm appearance on B-mode images was monitored every 2-3 days for 30 days. On the basis of B-mode images obtained after 30 days, aneurysms were deemed to have been unstable if they had ruptured; otherwise, they were deemed stable. Statistical significance was assessed by using two-tailed t tests. Results In normal aortas, the pulse waves propagated at relatively constant velocities (mean ± standard deviation, 2.8 m/sec ± 0.9). Fifteen days after infusion, all mice had developed aneurysms, with significant (P < .001/12) changes in maximum anterior-posterior diameter (increase of 54.9% ± 2.5) and pulse wave velocity (PWV) (decrease of 1.3 m/sec ± 0.8). While there was no significant difference in these parameters (P = .45 for diameter and P = .55 for PWV) between stable aneurysms (n = 12) and unstable aneurysms (n = 14), the standard deviation of the high-resolution PWV was significantly higher (P < .001/12) in unstable aneurysms (5.7 m/sec ± 1.6) than in stable ones (3.2 m/sec ± 0.9). Conclusion High-resolution PWI was used to measure the local homogeneity of pulse wave propagation within the saccular wall, which is lower in unstable aneurysms than in stable ones. Hence, if proven to add additional information beyond size and appearance in human studies, PWI could potentially be used to assess the stability of aneurysms by providing information that is complementary to the anatomic data obtained with conventional B-mode imaging. © RSNA, 2016 Online supplemental material is available for this article.


Solution self-assembly of magnetic light modulators from exfoliated perovskite and magnetite nanoparticles.
Covalent linkage of oleic acid ligated Fe3O4 spheres (9 nm) with sheetlike [H1-xCa2Nb3O10] particles (300 x 300 x 2 nm) yields, depending on conditions, submicro- or microscale stacks, which on their surfaces are decorated with magnetite nanoparticles. Due to the optical anisotropy of the sheetlike Ca2Nb3O10 building blocks and due to the superparamagnetic nature of the Fe3O4 components, the nanostructured composites exhibit magnetically controllable birefringence and light-scattering properties in solution.


A novel self-expanding biflanged metal stent vs tubular metal stent for EUS-guided transmural drainage of pancreatic pseudocyst: A retrospective, cohort study.
Although endoscopic ultrasound (EUS)-guided transmural drainage of pancreatic fluid collections with metal stents is generally preferred over plastic stents, its superiority among different types of metal stents has not yet been well studied. We conducted this study to compare clinical outcomes and complications of a novel self-expanding biflanged metal stent (BFMS) and a traditional-shaped tubular metal stent (TMS) in treating pancreatic pseudocyst (PPC).This was a retrospective analysis on consecutive patients with PPC underwent EUS-guided transmural drainage with either TMS or BFMS in a single tertiary center with expertise in management of complex biliary and pancreatic problems. The technical and functional success rate, reintervention, complications, and recurrence rate were evaluated.From September 2013 to January 2018, 125 patients (66.4% male, median age 47 years) underwent EUS-guided transmural drainage for PPC. Among them, 49 used TMS and 76 used BFMS. All patients met the inclusion criteria that cyst diameter was >6 cm or the distance between cyst and stomach wall was shorter than 1 cm. There was no difference in technical success (98% vs 97.4%, P = 1.0) or functional success rate (87.8% vs 92.1%, P = .54) using 2 types of metal stents. However, more procedure related complications occurred in TMS than in BFMS group. TMS group had a much higher migration rate than BFMS group (14.6% vs 0, P = .001), even though there was no significant difference in bleeding, infection, or death rate between 2 groups. With similar clinical outcomes, TMS group required more additional plastic stent placement than BFMS group for better drainage.TMS and BFMS placement can both be considered as methods of endoscopic transmural PPC drainage with equal efficacy, whereas BFMS could be preferred for fewer complications or less need of additional plastic stent placement.


Loss of Sprouty Produces a Ciliopathic Skeletal Phenotype in Mice Through Upregulation of Hedgehog Signaling.
The Sprouty family is a highly conserved group of intracellular modulators of receptor tyrosine kinase (RTK)-signaling pathways, which have been recently linked to primary cilia. Disruptions in the structure and function of primary cilia cause inherited disorders called ciliopathies. We aimed to evaluate Sprouty2 and Sprouty4 gene-dependent alterations of ciliary structure and to focus on the determination of its association with Hedgehog signaling defects in chondrocytes. Analysis of the transgenic mice phenotype with Sprouty2 and Sprouty4 deficiency revealed several defects, including improper endochondral bone formation and digit patterning, or craniofacial and dental abnormalities. Moreover, reduced bone thickness and trabecular bone mass, skull deformities, or chondroma-like lesions were revealed. All these pathologies might be attributed to ciliopathies. Elongation of the ciliary axonemes in embryonic and postnatal growth plate chondrocytes was observed in Sprouty2-/- and Sprouty2+/- /Sprouty4-/- mutants compared with corresponding littermate controls. Also, cilia-dependent Hedgehog signaling was upregulated in Sprouty2/4 mutant animals. Ptch1 and Ihh expression were upregulated in the autopodium and the proximal tibia of Sprouty2-/- /Sprouty4-/- mutants. Increased levels of the GLI3 repressor (GLI3R) form were detected in Sprouty2/4 mutant primary fibroblast embryonic cell cultures and tissues. These findings demonstrate that mouse lines deficient in Sprouty proteins manifest phenotypic features resembling ciliopathic phenotypes in multiple aspects and may serve as valuable models to study the association between overactivation of RTK and dysfunction of primary cilia during skeletogenesis. © 2021 American Society for Bone and Mineral Research (ASBMR).


Aberrant expression of miR-218 and miR-204 in human mesial temporal lobe epilepsy and hippocampal sclerosis-convergence on axonal guidance.
Mesial temporal lobe epilepsy (MTLE) is one of the most common types of the intractable epilepsies and is most often associated with hippocampal sclerosis (HS), which is characterized by pronounced loss of hippocampal pyramidal neurons. microRNAs (miRNAs) have been shown to be dysregulated in epilepsy and neurodegenerative diseases, and we hypothesized that miRNAs could be involved in the pathogenesis of MTLE and HS. miRNA expression was quantified in hippocampal specimens from human patients using miRNA microarray and quantitative real-time polymerase chain reaction RT-PCR, and by RNA-seq on fetal brain specimens from domestic pigs. In situ hybridization was used to show the spatial distribution of miRNAs in the human hippocampus. The potential effect of miRNAs on targets genes was investigated using the dual luciferase reporter gene assay. miRNA expression profiling showed that 25 miRNAs were up-regulated and 5 were down-regulated in hippocampus biopsies of MTLE/HS patients compared to controls. We showed that miR-204 and miR-218 were significantly down-regulated in MTLE and HS, and both were expressed in neurons in all subfields of normal hippocampus. Moreover, miR-204 and miR-218 showed strong changes in expression during fetal development of the hippocampus in pigs, and we identified four target genes, involved in axonal guidance and synaptic plasticity, ROBO1, GRM1, SLC1A2, and GNAI2, as bona fide targets of miR-218. GRM1 was also shown to be a direct target of miR-204. miR-204 and miR-218 are developmentally regulated in the hippocampus and may contribute to the molecular mechanisms underlying the pathogenesis of MTLE and HS.


Hydration Effect on Positron Binding Ability of Proline: Positron Attachment Induces Proton-Transfer To Form Zwitterionic Structure.
The positron binding abilities of proline and its hydrated clusters were theoretically studied using multicomponent molecular orbital (MC_MO) calculations. Low-lying equilibrium structures of the neutral proline·(H2O) n ( n = 0-2) clusters were systematically explored with the aid of global reaction route mapping code. The positron binding energies were then calculated for the equilibrium structures. We found that the zwitterionic forms generally displayed high positron binding energies owing to their highly polar nature. We also found that nonzwitterionic forms can exhibit high positron binding energies if the addition of water significantly increases the total electric dipole moment. These results demonstrate that the most stable positron-bound proline·(H2O) n ( n = 1 and 2) structures are more stable than the most stable neutral structures, which implies that the attachment of a positron to a neutral hydrated proline cluster can induce structural changes if the positron-electron annihilation lifetime is sufficiently long relative to the time scale of nuclear motion. We also examined the influence of positron binding on the energy profiles of the proton transfer reactions from the nonzwitterionic form to the zwitterionic form.


Population and molecular genetics of susceptibility to tuberculosis.
Genetic influences on the course of mycobacterial infections during epidemics and in the endemic areas have always been suspected, but the precise nature of such genetic control and of the inherited mechanisms of susceptibility has been unknown. We have used the methods of population genetics in the mouse to discover a single dominant autosomal gene which controls the susceptibility to tuberculosis. The phenotypic expression of this gene has been defined as the nonspecific macrophage activation for bactericidal function. Using recombinant inbred strains we have mapped this gene to the centromeric part of Chromosome 1, and we have identified closely linked DNA polymorphisms (RFLP sites) which can be used as biochemical markers of innate susceptibility. It has recently become obvious that a homologous linkage group of RFLP sites is conserved in the bovine genome and also on the long arm (2q) of human Chromosome 2, suggesting the existence of a human homologue of the mouse host resistance gene. Experiments currently in progress test this hypothesis by linkage analysis of the trait of resistance and susceptibility to tuberculosis with the allelic forms of the 2q DNA markers. The identification of the human gene for susceptibility would be of major importance in the search for genetically susceptible individuals and in the development of novel strategies of specific prevention and treatment.


Aspergillus citrinoterreus, a new species of section Terrei isolated from samples of patients with nonhematological predisposing conditions.
The use of molecular identification techniques has revealed an increasing number of new species within Aspergillus section Terrei. We phenotyped a set of 26 clinical isolates that showed genetic differences from Aspergillus terreus sensu stricto by analyzing sequences from PCR-amplified β-tubulin and calmodulin genes and the internal transcribed spacer region. Since the isolates were phylogenetically and morphologically different from all of the members of Aspergillus section Terrei, they are described here as a new species, Aspergillus citrinoterreus, so named because it produces a diffusible yellowish pigment in agar. A. citrinoterreus isolates were significantly more susceptible to itraconazole, voriconazole, and posaconazole than A. terreus sensu stricto isolates were; in contrast, the amphotericin B MICs for both species were high. A. citrinoterreus was found in clinical samples from patients with proven or probable invasive aspergillosis and colonized patients, none of whom had hematological malignancies as predisposing conditions. However, they did have other underlying conditions such as chronic obstructive pulmonary disease, cirrhosis, and cancer or had received a solid organ transplants and presented not only with invasive pulmonary aspergillosis but also with mediastinitis. A. citrinoterreus isolates were detected for the first time in 2002. In all cases of invasive aspergillosis, A. citrinoterreus was found to be a copathogen, mostly with A. fumigatus.


The performance of random coefficient regression in accounting for residual confounding.
Greenland (2000, Biometrics 56, 915-921) describes the use of random coefficient regression to adjust for residual confounding in a particular setting. We examine this setting further, giving theoretical and empirical results concerning the frequentist and Bayesian performance of random coefficient regression. Particularly, we compare estimators based on this adjustment for residual confounding to estimators based on the assumption of no residual confounding. This devolves to comparing an estimator from a nonidentified but more realistic model to an estimator from a less realistic but identified model. The approach described by Gustafson (2005, Statistical Science 20, 111-140) is used to quantify the performance of a Bayesian estimator arising from a nonidentified model. From both theoretical calculations and simulations we find support for the idea that superior performance can be obtained by replacing unrealistic identifying constraints with priors that allow modest departures from those constraints. In terms of point-estimator bias this superiority arises when the extent of residual confounding is substantial, but the advantage is much broader in terms of interval estimation. The benefit from modeling residual confounding is maintained when the prior distributions employed only roughly correspond to reality, for the standard identifying constraints are equivalent to priors that typically correspond much worse.


Effects of tandospirone, a 5-HT1A receptor-related anxiolytic, on the pressor response elicited by stimulation of the posterior hypothalamus in cats.
The effects of tandospirone, a novel 5-HT1A receptor-related anxiolytic, on pressor responses elicited by activation of the posterior hypothalamus were examined in alpha-chloralose-anesthetized cats and compared with those of diazepam and tofisopam. Intravenous administration of tandospirone (0.1-1 mg/kg) and diazepam (1 mg/kg) markedly inhibited the pressor responses to stimulation of the posterior hypothalamus, but did not inhibit the pressor responses to intravenous norepinephrine. The inhibition of the posterior hypothalamus-induced pressor response by tandospirone was significantly antagonized by pindolol (a 5-HT1A receptor antagonist) but not by CGS-8216 (a benzodiazepine receptor antagonist), while the latter reduced the inhibitory effects of diazepam. Tofisopam (a 2,3-benzodiazepine which lacks affinity for benzodiazepine receptors) only attenuated the posterior hypothalamus-induced pressor responses at a high dose (10 mg/kg), which was sufficient to suppress the norepinephrine-induced pressor responses. These results indicate that tandospirone, diazepam and tofisopam all inhibit the pressor response to the posterior hypothalamus activation. In addition, tandospirone and diazepam exert this effect through different mechanisms, the former probably through 5-HT1A receptors and the latter through benzodiazepine receptors.


J-shaped Association between Serum Uric Acid Levels and the Prevalence of a Reduced Kidney Function: A Cross-Sectional Study Using Japanese Health Examination Data.
Objective While an association between a reduced kidney function and hyperuricemia has been reported, its association with hypouricemia is not well understood. The present study therefore investigated this association. Methods Using a large Japanese health examination dataset, we performed a multivariable logistic regression analysis to assess the association between serum uric acid (SUA) levels and a reduced kidney function. The covariates included the age, body mass index, alcohol intake, and the presence of hypertension, dyslipidemia, or diabetes. Patients This study included 227,672 patients (104,854 men; 46.1%), and the analyses were performed separately for men and women. The patients were classified into 5 groups: hypouricemia (SUA ≤2.0 mg/dL) (1st) and four other (2nd-5th) groups with SUA levels of ≤2.0, 2.1-5.1, 5.2-5.9, 6.0-6.8, ≥6.9 mg/dL in men and ≤2.0, 2.1-3.7, 3.8-4.4, 4.5-5.1, ≥5.2 mg/dL in women, respectively. Results The characteristics of the study population were as follows: men, age 55.9±14.9 years old, SUA 5.9±1.3 mg/dL, estimated glomerular filtration rate (eGFR) 80.0±17.2 mL/min/1.73 m2, and a reduced kidney function (eGFR<60.0 mL/min/1.73 m2) 9.4%; women, age 57.3±15.0 years old, SUA 4.5±1.1 mg/dL, eGFR 81.2±18.0 mL/min/1.73 m2, and a reduced kidney function 9.4%. Compared with the 2nd group, the other 4 groups groups had a significantly higher prevalence of a reduced kidney function [odds ratio (OR), 2.58; 95% confidence interval (CI), 1.64-4.06 in men; OR, 1.66; 95% CI, 1.16-2.39 in women]. Conclusion The prevalence of a reduced kidney function was high in both men and women in the hypouricemia and high-SUA groups. SUA levels and the prevalence of a reduced kidney function showed a J-shaped association.


The implication of the mineral ratios of Cucumis myriocarpus Naud. and Pergularia daemia (Forsk.) Chiov. in human diets.
Vegetables are considered to be the most affordable and sustainable sources of several micronutrients that are essential for physical and mental development, immune system functioning, and various metabolic processes in humans. However, their effectiveness as dietary sources of minerals is influenced by mineral-mineral interactions that may either enhance or reduce the absorption of certain micronutrients in the body. The awareness of such interactions, therefore, is useful when selecting vegetables that could help meet specific dietary criteria for improving micronutrient status. The purpose of this study was to investigate the suitability of Cucumis myriocarpus and Pergularia daemia as sources of mineral nutrients based on their mineral ratios for calcium, iron, potassium, and phosphorus. The Ca/Fe, Ca/K, Ca/Mg, and Ca/Zn ratios were 4.9, 0.9, 2.1, and 9.4, respectively, in C. myriocarpus. For P. daemia the same ratios were 1.7, 0.3, 1.6, and 9.7, respectively. A negative interaction was predicted between calcium and potassium, while the other calcium ratios were considered to be appropriate. The Fe/Zn ratio was adequate for C. myriocarpus (1.9) but excessive for P. daemia (5.6), while the K/Na ratio was good in both vegetables at 39.5 and 12.8, respectively. The P/Ca ratio was 0.2 in C. myriocarpus and 0.3 in P. daemia. Both wild vegetables could be promoted as natural sources for the minerals analyzed, but some adjustment of the P/Ca and Ca/K ratios would be required. Furthermore, the selection of P. daemia for either iron or zinc supplementation is not recommended because of the high Fe/Zn ratio.


Biofeedback therapy for migraine headaches.
We studied the biofeedback treatment of migraine headaches, attempting to control for some of the methodological limitations of previous work. Seven individuals suffering from migraine headache were trained in the usual finger warming procedure with the omission of autogenic phrases. Additionally, to control for placebo-expectance effects, three of these subjects received training in finger cooling prior to warming. With training in finger warming, headache activity was substantially reduced. In contrast, headache activity either remained at base line levels or increased during training in cooling despite positive therapeutic expectations. The results of this study indicate that finger temperature warming, without autogenic training, is effective in reducing migraine activity, independent of suggestion effects.


Bloodstream infections due to extended-spectrum β-lactamase-producing Enterobacteriaceae among patients with malignancy: a systematic review and meta-analysis.
Extended-spectrum β-lactamase-producing Enterobacteriaceae (ESBL-PE) are an increasing cause of resistant infections among patients with malignancy. This study sought to estimate the prevalence of bloodstream infections (BSIs) caused by ESBL-PE in this population and to examine regional and temporal differences. The PubMed and EMBASE databases (to 30 April 2016) were searched to identify studies reporting ESBL-PE BSI rates among patients with malignancies. Of 593 non-duplicate reports, 22 studies providing data on 5650 BSI cases satisfied the inclusion criteria. Among all BSIs the pooled prevalence of ESBL-PE was 11% (95% CI 8-15%) and among Gram-negative BSIs it was 21% (95% CI 16-27%). Among patients with haematological malignancies, the pooled ESBL-PE prevalence was 11% (95% CI 8-15%), whereas no studies providing specific data on patients with solid tumours were identified. Stratifying per geographic region, the pooled prevalence was 7% each in Europe (95% CI 5-11%), the Eastern Mediterranean region (95% CI 4-11%) and South America (95% CI 2-14%), 10% in the Western Pacific region (95% CI 4-19%) and 30% in Southeast Asia (95% CI 18-44%). Importantly, there was a 7.1% annual increase in the ESBL-PE incidence (P = 0.004). Overall, ca. 1 in 10 BSIs in patients with malignancy is caused by ESBL-PE and in some areas this rate can be as high as 1 in 3 cases. Additionally, the incidence of these resistant infections is rising. These findings should be considered when selecting empirical antimicrobial therapy and should prompt strict adherence to antimicrobial stewardship.


Sexual behaviour, drug use and health service use by young Noongar people in Western Australia: a snapshot.
Background This study aimed to describe sexual health behaviour, alcohol and other drug use, and health service use among young Noongar people in the south-west of Western Australia. A cross-sectional survey was undertaken among a sample of 244 Noongar people aged 16-30 years. The sample was more disadvantaged than the wider Noongar population. Sexual activity was initiated at a young age, 18% had two or more casual sex partners in the previous 12 months, with men more likely to have done so than women (23% vs 14%). Condoms were always or often carried by 57% of men and 37% of women, and 36% of men and 23% of women reported condom use at last sex with a casual partner. Lifetime sexually transmissible infection diagnosis was 14%. Forty percent currently smoked tobacco and 25% reported risky alcohol consumption on a weekly and 7% on an almost daily basis. Cannabis was used by 37%, 12% used drugs in addition to cannabis and 11% reported recently injecting drugs. In the previous 12 months, 66% had a health check and 31% were tested for HIV or sexually transmissible infections. Additionally, 25% sought advice or assistance for mental health or alcohol and other drug issues. Although some respondents engaged in risky sexual behaviour, alcohol and other drug use or both, most did not. Particularly encouraging was the engagement of respondents with the health care system, especially among those engaging in risky behaviours. The results confound negative stereotypes of Aboriginal people and demonstrate a level of resilience among respondents.


[Translation and Development of the Chinese-Version Patient Privacy Scale].
The unauthorized releasing of confidential patient information is a serious problem worldwide. Nurses, the healthcare professionals who are in most frequent contact with patients, have access to a significant amount of confidential patient information and play a key role in protecting patient privacy. However, currently, there is no proper tool to measure the level to which clinical nurses protect the privacy of their patients in China. To translate the patient privacy scale (PPS) into Chinese and to test the reliability and validity of this Chinese version. The original scale was developed by Özturk, Bahcecik, and Özçelik (2014) to identify whether nurses protect or violate patient privacy in the workplace. This study used the "back translation" method to translate the scale. A total of 616 nurses in two tertiary hospitals in the Western region of China were enrolled to test the internal consistency, test-retest reliability, and construct validity of the translated scale. The Cronbach's coefficients of the total scale and its 5 factors ranged from .84 to .94; the split half reliability was .91; the test-retest reliability was .82; and the content validity index was .95. Explanatory factor analysis revealed that the 5 factors explained 64.98% of the total variance. The Chinese version of the PPS is reliable and valid, and may be used to reliably assess the behaviors of nurses with regard to protecting the privacy of their patients. The scale may also be used to evaluate the effects of training on patient privacy protection.


Colivelin Ameliorates Impairments in Cognitive Behaviors and Synaptic Plasticity in APP/PS1 Transgenic Mice.
Alzheimer's disease (AD) is the most common cause of dementia, and effective therapeutics are lacking. Colivelin (CLN), a novel, strong humanin derivative, is effective in vitro in preventing cell death induced by AD-causative genes and amyloid-β protein (Aβ) even at a low concentration. We recently demonstrated that intrahippocampal injection of CLN prevents Aβ25-35-induced deficits in spatial memory and synaptic plasticity in normal rats. Here, we further observed the effects of chronically intranasally (i.n.) administered CLN on cognitive behaviors and pathological hallmarks in 9-month-old APPswe/PS1dE9 (APP/PS1) AD mice using multiple behavioral tests and immunochemistry. The electrophysiological mechanism of CLN neuroprotection was also investigated by recording in vivo hippocampal long-term potentiation (LTP). CLN pretreatment effectively prevented impairments in new object recognition, working memory, and long-term spatial memory and reversed the depression of in vivo hippocampal LTP in APP/PS1 mice. Additionally, chronic application of CLN obviously reduced Aβ deposition in the hippocampus in APP/PS1 mice. These results indicate that CLN has strong neuroprotective effects on learning and memory behaviors in APP/PS1 mice and that this behavioral improvement is closely associated with the reduction of Aβ deposition and alleviation of LTP suppression in the hippocampus, supporting the potential of CLN for the prevention and treatment of AD.


Health visitors have much to offer pre-registration child branch student nurses.
The primary care workforce has recently become the focus of several reports, which highlight the preparation and upskilling of nurses for a move to acute care in the community and plans to widen the community and primary care workforce. This paper explores current health plans in relation to pre-registration nurse education and identifies the health visitor as having key qualities and skills to manage child branch student nurses' community placements. A health visitor's perspective reinforces the discussion and highlights how the current climate offers a valuable opportunity for health visitors to promote a positive learning environment. Numerous learning opportunities are identified in the community placement, which can serve to equip student nurses with key nursing and interprofessional skills, such as leadership, management, assessment, communication and negotiation. A student's perspective is offered to provide an example of how a positive experience in the community can enhance student learning. This discussion concludes that the health visitor can be a valuable mentor to offer pre-registration student nurses a supportive environment in which to identify their strengths and weaknesses, and encourage students to flourish as caring and compassionate nurses.


The value of potential immunohistochemical biomarkers and clinicopathological findings in predicting response to neoadjuvant chemotherapy in breast cancer.
Following neoadjuvant chemotherapy (NAC) in breast cancer (BC), complete treatment response is achieved in some patients, while treatment response is limited in others. Predicting non-responder patients can prevent exposure to adverse effects associated with chemotherapeutic agents and delays in selecting other treatment modalities. In this study, we aimed at identifying predictive factors related to tumor regression in patients with BC who received NAC. This single-center cohort included 91 patients with BC who underwent surgery following NAC based on pretreatment tumor biopsy. According to BC molecular subtype, tumor regression grade (TRG) was determined using the Miller-Payne scoring system in patients who received standard NAC. Immunohistochemical stainings for VEGFR3 and CD44 were applied to needle core biopsies obtained prior to NAC in these patients. Pathological complete response (pCR) was achieved in 20 patients (22%). In univariate analysis, high Ki-67 expression, ER negativity, and HER2 positivity were determined to be predictive factors of TRG (p < 0.05). In multivariate analysis, Ki-67 was the single independent predictor of TRG, with a 1.05-fold effect size. CD44 and VEGFR3 levels did not affect TRG or survival (p > 0.05). There was a significant difference in TRG according to molecular subtype of BC (p < 0.001). The treatment response was 5.5-fold higher in HER2-positive patients compared with HER2-negative patients. pCR rates were significantly higher in TNBC, HER2, and luminal HER2+ subtypes when compared with luminal HER2- subtype. Ki-67 >25% and ER negativity had a favorable effect on TRG after NAC. CD44 and VEGFR3 were not effective in predicting treatment response.


Dosimetry of a Carbon Dioxide Laser for Black Tattoo Removal in a Rat Model.
Objective: To determine the optimal parameters of power, energy, and time for the application of a carbon dioxide laser for Tribal Black ink tattoo removal. Background data: The use of antiquated techniques to remove tattoos demonstrates the difficulty of making advances in this field. Studies by the American Society for Dermatologic Surgery have shown that 5% of the global population has at least one tattoo on the body, with 10% of them wanting a tattoo to be removed. Laser removal has been studied and improved as a less invasive and safer method of surgical removal; however, the ideal dosimetry is not yet established. Materials and methods: Thirty-three male Wistar rats were anesthetized and tattooed in the dorsal region in a quadrangular manner. The rats were distributed under low/null luminosity for 4 months into three equal and random groups for the application of the laser, namely, G1 (P = 0.6 W, Et = 0.9 J), G2 (P = 0.8 W, Et = 1, 2 J), and G3 (P = 1 W, Et = 1.5 J), with the application time standardized to 0.15 sec with 10 passes per application. The procedure was repeated at intervals of 4 weeks until 10 cycles of laser application were completed. The images were studied using the ImageJ program and histological analysis and subjected to the one-way ANOVA test for Tukey's multiple comparison post-test. Results: We observed a significant difference between groups 1 and 3 and between groups 2 and 3. Conclusions: The laser with the parameters of P = 1 W, Et = 1.5 J, and t = 0.15 sec yields better Tribal Black ink removal results.


Toxicity and biodegradation of diamines.
Phytotoxicity and cytotoxicity of 2,4-diaminotoluene (2,4-D), 4,4'-methylenedianiline (4,4-D), and 1,6-hexanediamine (1,6-D) were investigated by observing the germination of young radish seeds and the viability of HeLa cells, respectively. 2,4-D showed the highest, 4,4-D intermediate, and 1,6-D lowest cytotoxicity. However, the phytotoxicity decreased in the order of 4,4-D > 2,4-D > 1,6-D. Contrary to the results previously reported, in the modified Sturm test the activated sludge degraded 2,4-D and 4,4-D as well as 1,6-D without any pre-acclimation. Ochrobacterium antropi was isolated for degradation of 2,4-D and 4,4-D and Pseudomonas citronellolis for 1,6-D degradation. Thielevia sp. was isolated as 2,4-D degrading fungus and Aspergillus sp. as 4,4-D and 1,6-D degrading fungus. The fungi degraded the diamines faster than the bacteria.


Combined retrograde stent-graft placement and surgical repair for a Stanford type A aortic dissection.
To report a case of retrograde acute Stanford type A aortic dissection treated without hypothermic circulatory arrest. A 55-year-old man presented with a retrograde acute type A aortic dissection with an entry tear 30 mm below the left subclavian artery. A concurrent emergent endovascular and surgical treatment was performed, excluding the entry tear with retrograde delivery of a stent-graft and replacing the ascending aorta with a Dacron tube without circulatory arrest. Avoiding hypothermic circulatory arrest was the main advantage of this hybrid therapeutic choice. This combined technique may be of interest in acute retrograde type A dissections that present complications such as impending rupture or visceral malperfusion. A close collaboration between endovascular specialists and cardiac surgeons is essential for such a hybrid strategy.


fMRI data of mixed gambles from the Neuroimaging Analysis Replication and Prediction Study.
There is an ongoing debate about the replicability of neuroimaging research. It was suggested that one of the main reasons for the high rate of false positive results is the many degrees of freedom researchers have during data analysis. In the Neuroimaging Analysis Replication and Prediction Study (NARPS), we aim to provide the first scientific evidence on the variability of results across analysis teams in neuroscience. We collected fMRI data from 108 participants during two versions of the mixed gambles task, which is often used to study decision-making under risk. For each participant, the dataset includes an anatomical (T1 weighted) scan and fMRI as well as behavioral data from four runs of the task. The dataset is shared through OpenNeuro and is formatted according to the Brain Imaging Data Structure (BIDS) standard. Data pre-processed with fMRIprep and quality control reports are also publicly shared. This dataset can be used to study decision-making under risk and to test replicability and interpretability of previous results in the field.


Low temperature magnetic structure of CeRhIn5 by neutron diffraction on absorption-optimized samples.
Two aspects of the ambient pressure magnetic structure of heavy fermion material CeRhIn5 have remained under some debate since its discovery: whether the structure is indeed an incommensurate helix or a spin density wave, and what is the precise magnitude of the ordered magnetic moment. By using a single crystal sample optimized for hot neutrons to minimize neutron absorption by Rh and In, here we report an ordered moment of [Formula: see text]. In addition, by using spherical neutron polarimetry measurements on a similar single crystal sample, we have confirmed the helical nature of the magnetic structure, and identified a single chiral domain.


Disruption of virus movement confers broad-spectrum resistance against systemic infection by plant viruses with a triple gene block.
White clover mosaic virus strain O (WClMV-O), species of the Potexvirus genus, contains a set of three partially overlapping genes (the triple gene block) that encodes nonvirion proteins of 26 kDa, 13 kDa, and 7 kDa. These proteins are necessary for cell-to-cell movement in plants but not for replication. The WClMV-O 13-kDa gene was mutated (to 13*) in a region of the gene that is conserved in all viruses known to possess triple-gene-block proteins. All 10 13* transgenic lines of Nicotiana benthamiana designed to express the mutated movement protein were shown to be resistant to systemic infection by WClMV-O at 1 microgram of WClMV virions per ml, whereas all plants from susceptible control lines became systemically infected. Of the 13* transgenic lines, 3 selected for their abundant seed supply were shown to be resistant to systemic infection when challenged by inoculation with three different WClMV strains (O, M, and J) or with WClMV-O RNA at 10 micrograms/ml. Most plants were also resistant to systemic infection at inoculum concentrations up to 250 micrograms of WClMV virions per ml. In addition, the three 13* transgenic plant lines were found to be resistant to systemic infection with two other members of the Potexvirus group, potato virus X and narcissus mosaic virus, and the Carlavirus potato virus S but not to be resistant to tobacco mosaic virus of the Tobamovirus group. These results indicate that virus resistance can be engineered into transgenic plants by expression of dominant negative mutant forms of triple-gene-block movement proteins.


Are the 2-isomers of the drug rimantadine active anti-influenza A agents?
There is a lack of information in the medical chemistry literature concerning the anti-influenza A activity of the drug rimantadine's 2-isomer (2-rimantadine). We now present results showing that, although 2-adamantanamine (2-amantadine) 3 is only moderately active, some 2-rimantadine analogues are effective anti-influenza A virus agents in vitro. The 2-rimantadine analogues and their spirocyclobutane and spirocyclopentane congeners were synthesized through interesting routes. The 2-rimantadine analogues were 2-4 times more potent than rimantadine 2 against influenza virus A H2N2 strain; their spirocyclobutane congeners proved equally active to rimantadine 2. Two compounds exhibited a similar activity and one of the compounds was was fourfold more potent than rimantadine 2 against H3N2 strain.


beta-Adrenoceptor density and adenylyl cyclase activity in obese rabbit hearts.
To determine whether decreased cardiac responsiveness to isoproterenol in obesity is associated with alterations in beta-receptors and/or adenylyl cyclase activity. ANIMALS AND DESIGN: After 12 weeks of control or ad libitum high-fat diets, left ventricular tissue from lean and obese female New Zealand white rabbits was assayed for beta-receptor binding density (11 lean, 11 obese) and isoproterenol-stimulated adenylyl cyclase activity (eight lean, 10 obese). Nonlinear least squares regression analysis was used to determine maximum density of beta-receptors and receptor affinity for (125)I-iodocyanopindolol. Four-parameter logistic regression was used to determine minimum, maximum, slope and EC(50) for isoproterenol-stimulated adenylyl cyclase activity. Obese rabbits had elevated resting blood pressure and heart rate, and higher ventricular weights. However, beta-adrenoceptor density and affinity were not significantly different in lean and obese rabbits. Basal and maximum isoproterenol-stimulated adenylyl cyclase activity did not differ between lean and obese rabbits. In addition, maximal stimulation in response to sodium flouride did not differ between lean and obese. EC(50) for isoproterenol-stimulated adenylyl cyclase activity did not differ between lean and obese rabbits. Obesity-related decreases in responsiveness of the isolated heart to isoproterenol are not associated with alterations in beta-receptor density and affinity. In addition, adenylyl cyclase activity appeared unchanged in ventricular preparations from obese rabbits. Decreased responsiveness to isoproterenol in obesity may be due to defects downstream of adenylyl cyclase activation of cyclic AMP.


Pediatric Pelvic Ring Injuries.
The purpose of this study was to determine whether pelvic fracture pattern is associated with transfusion requirements or concomitant injuries in pediatric patients. This was a single-institution, retrospective review from 1970 to 2000. Pelvic ring injuries were classified using the Orthopaedic Trauma Association system. Injury Severity Scores were assigned. Ninety patients were included in this study. There were 27 A-type (30.0%), 51 B-type (56.7%), and 12 C-type (13.3%) injuries. Mean Injury Severity Scores were 8.1 for 61 A-type, 12.7 for 61 B-type, and 23.6 for 61 C-type fractures (P<.0001). Transfusion was required for 14.8% of A-type, 18.4% of B-type, and 66.7% of C-type injuries (P=.0009). There was no significant association with the number of units transfused (P=.9614). Decreased pelvic ring fracture stability was associated with an increased need for blood transfusion, although not with the number of units. Pelvic ring fracture stability may be a marker of associated injuries. [Orthopedics. 2018; 41(5):e701-e704.].


"You just have to live with it": coping with sickle cell disease in Jamaica.
Research has shown that living with sickle cell disease (SCD) can be a considerable challenge. Unfortunately, although it is Jamaica's most common genetic disorder, to date, no qualitative research has been conducted on Jamaicans' experiences of SCD. We conducted thematic analysis on transcripts of in-depth semistructured interviews with 30 patients and found two interlinked themes bound up in life with SCD: loss and control. Faced with important losses, respondents used cognitive and behavioral coping strategies to reestablish control over their response to SCD, others' responses to SCD, and SCD's physical manifestations. Although the adaptive nature of some of these strategies is debatable, many facilitate management of the illness. Health care practitioners should encourage positive coping strategies and have nonjudgmental discussions with patients about (potentially) negative ones. They should also share information with nonspecialist doctors and nurses to reduce stigmatization around the illness. More exploration of this underresearched topic is needed.


Cryptococcal Meningitis in an Immunocompetent Patient with a Ventriculo-Pleural Shunt.
Cryptococcal meningitis is the most common form of infection caused by Cryptococcus yeast species, followed by pulmonary infection. It is an opportunistic infection seen in patients with impaired cell immunity, most frequently in HIV patients and solid organ transplant recipients; however, it can occur in patients with no apparent immunodeficiency. We describe the case of Cryptococcus neoformans meningitis in an immunocompetent patient with aseptic cerebrospinal fluid analysis which highlights the heterogeneity of this disease.


Streptomyces lividans 66 produces a protease inhibitor via a tRNA-utilizing enzyme interacting with a C-minus NRPS.
Small peptide aldehydes (SPAs) with protease inhibitory activity are naturally occurring compounds shown to be synthesized by non-ribosomal peptide synthetases (NRPS). SPAs are widely used in biotechnology and have been utilized as therapeutic agents. They are also physiologically relevant and have been postulated to regulate the development of their producing microorganisms. Previously, we identified an NRPS-like biosynthetic gene cluster (BGC) in Streptomyces lividans 66 that lacked a condensation (C) domain but included a tRNA-utilizing enzyme (tRUE) belonging to the leucyl/phenylalanyl (L/F) transferase family. This system was predicted to direct the synthesis of a novel SPA, which we named livipeptin. Using evolutionary genome mining approaches, here, we confirm the presence of L/F transferase tRUEs within the genomes of diverse Streptomyces and related organisms, including fusions with the anticipated C-minus NRPS-like protein. We then demonstrate genetic functional cooperation between the identified L/F-transferase divergent tRUE homolog with the C-minus NRPS, leading to the synthesis of a metabolic fraction with protease inhibitory activity. Semisynthetic assays in the presence of RNAse revealed that the productive interaction between the tRUE and the C-minus NRPS enzymes is indeed tRNA dependent. We expect our findings to boost the discovery of SPAs, as well as the development of protease-mediated biotechnologies, by exploiting the uncovered genetic basis for synthesizing putative acetyl-leu/phe-arginine protease inhibitors. Furthermore, these results will facilitate the purification and structural elucidation of livipeptin, which has proven difficult to chemically characterize. The discovery of natural products biosynthetic genes marks a significant advancement in our understanding of these metabolites, for example of their evolution, activity, and biosynthesis, but also opens biotechnological opportunities and knowledge to advance genome mining approaches. We made this possible by uncovering a new biosynthetic pathway in Streptomyces lividans 66 shown to direct the synthesis of a strong protease inhibitor, termed livipeptin, following unprecedented biosynthetic rules and genes. Thus, by shedding light on the genetic mechanisms predicted to govern the production of acetyl-leu/phe-arginine protease inhibitors, including the elusive livipeptin, this study enables novel protease-mediated biotechnologies as well as approaches for discovering protease inhibitors from genome data.


Epidemiology of a toxoplasmosis outbreak in a research institution in northern Paraná, Brazil.
Toxoplasmosis is a reportable disease in Brazil. The objective of this study was to investigate a toxoplasmosis outbreak at a research institution in Londrina-PR, Brazil. The outbreak was reported in October 2015; however, the first cases occurred in August 2015. Blood samples were collected from 674 persons at the institution. Samples were collected from soil, water (water tank) and food (vegetables) served in the restaurant. Each participant responded to an epidemiological questionnaire. For the blood samples, a chemiluminescent microparticle immunoassay was performed to detect IgM, IgG and specific IgG avidity antibodies; 10.8% (73/674) had evidence of acute toxoplasmosis. Statistical analysis showed a significant association (p < .001) between acute infection and eating lunch in the restaurant of the institution. Regarding the types of food offered in the restaurant during the period, there was a significant association between consuming raw salad (p < .001) and becoming ill. We conclude that the vegetables or raw vegetables served in the restaurant were probably the source of infection; however, the long period between exposure and case reporting made it difficult to identify the source of transmission.


Immediate Versus Delayed Loading of Implant for Replacement of Missing Mandibular First Molar: A Randomized Prospective Six Years Clinical Study.
Emergence of dental implants made the replacement of missing tooth easy. During the early days of introduction, implants were loaded three to six months after implant insertion, but understanding of healing cascade and improved production technology has changed the phase of restoration from delayed to immediate loading. To evaluate and compare the clinical outcome of immediate and delayed loaded implant supported prosthesis for missing mandibular first molar. The objectives were bleeding on probing, probing depth, implant mobility, marginal bone level and peri-implant radiolucency were evaluated during follow up period. Twenty patients were included in this study who were in the need of fixed implant supported prosthesis for missing mandibular first molar. Single tooth implant with immediate loading done within two days of implant insertion in one group and another group were loaded after three months of implant insertion. These groups were evaluated clinically and radiographically over a period of 72 months after loading using Wilcoxon matched pairs test and Mann-Whitney U test. The study consists of 14 male and six female patients with the age range of 19 to 31 years. There was no bleeding on probing and probing depth remained well within the normal range even after 72 months of loading among both the groups. Minimal marginal bone loss observed with no mobility and peri-implant radiolucency. Implant supported prosthesis for missing mandibular first molar with immediate loading can be used as a successful treatment modality. It reduces treatment time, provides early function and prevents undue migration of adjacent tooth. Immediate loading showed similar clinical and radiographic results as that of delayed loading, indicating it as an equally efficient technique for implant supported prosthesis.


[Arthroscopy of the wrist].
Wrist arthroscopy may add specific datas to that provided by standard or motion view radiographs, arthrography, bone scan, TDM or RMN. Eight portals allow direct visualization of articular surfaces of radio-carpal and medio-carpal joints, triangular fibrocartilage, spaces between the carpal bones, interosseous and extrinsic ligaments. Wrist arthroscopy may be useful to evaluate lesions involving ligaments or cartilages, in degenerative or post-traumatic conditions. Arthroscopy may help to the decision in treatment of carpal instabilities, scaphoid pseudarthrosis, or Kienbock disease. Operative arthroscopy may allow shaving of damaged cartilage or fibrocartilage, bone resection or triangular fibrocartilage reinsertion.


[Local negative pressure and magnetic field in therapy of patients with erectile dysfunction].
Combined treatment with local negative pressure and pulsating magnetic field conducted in 116 patients with erectile dysfunction aged 20-60 years produced optimal treatment results. Recovery and improvement of the erectile function were achieved in 85.7% patients given local vacuum-magnetotherapy.


Electrically controlled microvalves to integrate microchip polymerase chain reaction and capillary electrophoresis.
Microvalves are key in realizing portable miniaturized diagnostic platforms. We present a scalable microvalve that integrates well with standard lab on a chip (LOC) implementations, yet which requires essentially no external infrastructure for its operation. This electrically controlled, phase-change microvalve is used to integrate genetic amplification and analysis via capillary electrophoresis--the basis of many diagnostics. The microvalve is actuated using a polymer (polyethylene glycol, PEG) that exhibits a large volumetric change between its solid and liquid phases. Both the phase change of the PEG and the genetic amplification via polymerase chain reaction (PCR) are thermally controlled using thin film resistive elements that are patterned using standard microfabrication methods. By contrast with many other valve technologies, these microvalves and their control interface scale down in size readily. The novelty here lies in the use of fully integrated microvalves that require only electrical connections to realize a portable and inexpensive genetic analysis platform.


Role of genetic modifiers in an orthologous rat model of ARPKD.
Human data and animal models of autosomal recessive polycystic kidney disease (ARPKD) suggest that genetic factors modulate the onset and severity of the disease. We report here for the first time that ARPKD susceptibility is attenuated by introgressing the mutated Pkhd1 disease allele from the polycystic kidney (PCK) rat onto the FHH (Fawn-Hooded Hypertensive) genetic background. Compared with PCK, the FHH.Pkhd1 strain had significantly decreased renal cyst formation that coincided with a threefold reduction in mean kidney weights. Further analysis revealed that the FHH. Pkhd1 is protected from increased blood pressure as well as elevated plasma creatinine and blood urea nitrogen levels. On the other hand, liver weight and biliary cystogenesis revealed no differences between PCK and FHH.Pkdh1, indicating that genes within the FHH genetic background prevent the development of renal, but not hepatic, manifestations of ARPKD. Microarray expression analysis of kidneys from 30-day-old PCK rats revealed increased expression of genes previously identified in PKD renal expression profiles, such as inflammatory response, extracellular matrix synthesis, and cell proliferation genes among others, whereas the FHH.Pkhd1 did not show activation of these common markers of disease. This newly developed strain can serve as a tool to map modifier genes for renal disease in ARPKD and provides further insight into disease variability and pathophysiology.


Detection of 5-hydroxytryptamine in developing sea urchin embryos.
5-Hydroxytryptamine has been determined in developing sea urchin embryos by means of chemical methods. An increase of the 5-hydroxytryptamine content can be correlated with the formation of neurons which occurs in the advanced gastrula and in young pluteus.


Long-term efficacy, safety, and tolerability of indinavir-based therapy in protease inhibitor-naive adults with advanced HIV infection.
A double-blind, randomized study of zidovudine-experienced, PI- and lamivudine-naive adults with baseline CD4 cell counts of < or =50 cells/mm3 had demonstrated that the HIV suppression achieved with zidovudine, lamivudine, and indinavir therapy was superior to that achieved with dual-nucleoside or indinavir-only regimens after 24 weeks of therapy. In a 192-week extension of the study, 371 participants received open-label indinavir with or without other antiretroviral drugs. One hundred and eight subjects were originally randomized to receive triple therapy. After 216 weeks, the proportion of subjects with HIV RNA levels of <500 copies/mL were 34%, according to a general estimating equation analysis, 92%, according to an observed data analysis, and 24%, according to an intention-to-treat analysis counting noncompleters as failures; the proportions of subjects with HIV RNA levels of <50 copies/mL were 31%, 85%, and 22%, respectively. Hyperbilirubinemia (experienced by 31% of subjects), nausea (17%), abdominal pain (14%), and nephrolithiasis (13%) were the most common drug-related adverse events during the extension.


Relating Structure and Dynamics in RNA Biology.
Recent advances in structural biology methods have enabled a surge in the number of RNA and RNA-protein assembly structures available at atomic or near-atomic resolution. These complexes are often trapped in discrete conformational states that exist along a mechanistic pathway. Single-molecule fluorescence methods provide temporal resolution to elucidate the dynamic mechanisms of processes involving complex RNA and RNA-protein assemblies, but interpretation of such data often requires previous structural knowledge. Here we highlight how single-molecule tools can directly complement structural approaches for two processes--translation and reverse transcription-to provide a dynamic view of molecular function.


Osteoarticular involvement in childhood brucellosis: experience with 133 cases in an endemic region.
To describe the main clinical and laboratory characteristics, frequency and distribution of osteoarticular involvement, therapeutic options and outcome in children with osteoarticular brucellosis. This descriptive study includes 133 pediatric patients with osteoarticular brucellosis who were treated at the University Clinic for Infectious Diseases and Febrile Conditions in Skopje, Republic of Macedonia, during the period between 1989 and 2011. Brucellosis was presumptively diagnosed on the basis of clinical signs and confirmed by the detection of specific antibodies at significant titers. The median age of patients was 9 years (range, 2-14 years) and 63.9% were males. Family history of brucellosis was present in 54.1%. The dominant clinical symptoms were arthralgia and fever in 77.4% and 73.7%, respectively, and the dominant sign was hepatomegaly in 73.7% of patients. The main laboratory abnormalities were elevated C-reactive protein (81.0%) and circulating immunocomplexes (80.7%). In 71.4% of patients, the osteoarticular involvement was monoarticular. Hip arthritis was present in 49.6%, followed by the knee in 30.1%. Various therapeutic regimens with a duration of 6 weeks were used. In 87 patients during a follow-up of at least 6 months, relapse occurred in 13.8%. Osteoarticular involvement is frequent in children with brucellosis. It is most often manifested with monoarthritis of the large weight-bearing joints. Brucellosis should be included in the differential diagnosis of childhood arthritis in endemic countries, especially in the presence of family history, contact with infected animals or ingestion of unpasteurized food products, fever and hepatomegaly.


Free Radical Scavenging Activity of Calotropis gigantea on Streptozotocin-Induced Diabetic Rats.
Swarnabhasma, an Ayurvedic preparation containing Calotropis gigantea R. Br. (Asclepiadaceae) is extensively used by Ayurvedic physicians for treatment of diabetes mellitus, bronchial asthma, rheumatoid arthritis and nervous disorders. In the present study, we report the effect of chloroform extracts of Calotropis gigantea leaf and flower on free radical scavenging activity, and lipid profile in streptozotozin-induced diabetic rats. The lipid peroxidation, superoxide dismutase, and catalase were measured in liver homogenate and serum glutamic pyruvic transaminase, serum glutamic oxaloacetic transaminase, alkaline phosphatase, lipid profile were measured in blood serum. Administration of single dose of streptozotozin (55 mg/kg, i.p.) caused significant increases in lipid peroxidation, serum glutamic pyruvic transaminase, serum glutamic oxaloacetic transaminase, alkaline phosphatase, cholesterol and triglyceride levels, while superoxide dismutase and catalase levels were significantly decreased. Further, administration of chloroform extracts of Calotropis gigantea leaf and flower to streptozotocin-induced diabetes rats at a dose of 10, 20 and 50 mg/kg orally for 27 d lead to a significant decrease in lipid peroxidation, serum glutamic pyruvic transaminase, serum glutamic oxaloacetic transaminase, alkaline phosphatase, cholesterol and triglyceride levels. Consequently, superoxide dismutase and catalase levels were significantly increased. Glibenclamide was used as a positive control (10 mg/kg). It was observed that the effect of chloroform extracts of Calotropis gigantea on alkaline phosphatase, cholesterol, superoxide dismutase, serum glutamic pyruvic transaminase, serum glutamic oxaloacetic transaminase, levels are comparable to that of those produced by the positive control.


Health Experiences Research as a Resource and Mechanism for Veteran Engagement in VA Healthcare Research and Care Delivery.
Engaging patients in the research process helps to ensure researchers ask meaningful questions and generate useful evidence to inform healthcare decisions. In 2015, the Veterans Health Administration (VA) Health Services Research & Development (HSR&D) service convened a Veteran engagement workgroup, comprised of researchers, clinicians, and Veterans, to identify ways to integrate Veteran engagement into HSR&D. A subgroup was designated to explore the utility of health experiences research (research focused on enhancing understanding of people's experiences with healthcare and illnesses) as a mechanism to complement and broaden traditional engagement mechanisms. The subgroup recommended the VA adopt the Database of Individual Patient Experiences (DIPEx) methodology for conducting and disseminating health experiences research (HER). In this paper, we describe (1) the key components of the DIPEx approach, (2) how these components complement and broaden current methods of Veteran engagement, (3) an update on VA activities using the DIPEx approach, and (4) a roadmap for future VA HER activities.


Subsynaptic positioning of AMPARs by LRRTM2 controls synaptic strength.
Recent evidence suggests that nano-organization of proteins within synapses may control the strength of communication between neurons in the brain. The unique subsynaptic distribution of glutamate receptors, which cluster in nanoalignment with presynaptic sites of glutamate release, supports this hypothesis. However, testing it has been difficult because mechanisms controlling subsynaptic organization remain unknown. Reasoning that transcellular interactions could position AMPA receptors (AMPARs), we targeted a key transsynaptic adhesion molecule implicated in controlling AMPAR number, LRRTM2, using engineered, rapid proteolysis. Severing the LRRTM2 extracellular domain led quickly to nanoscale declustering of AMPARs away from release sites, not prompting their escape from synapses until much later. This rapid remodeling of AMPAR position produced significant deficits in evoked, but not spontaneous, postsynaptic receptor activation. These results dissociate receptor numbers from their nanopositioning in determination of synaptic function and support the novel concept that adhesion molecules acutely position receptors to dynamically control synaptic strength.


Updated racial disparities in incidence, clinicopathological features and prognosis of hypopharyngeal squamous carcinoma in the United States.
This study was to determine the racial disparities in incidence, clinicopathological features and prognosis of hypopharyngeal squamous cell carcinoma (HPSCC) in the US. The National Program of Cancer Registries and Surveillance, Epidemiology, and End Results (SEER) database was used to determine racial disparity in age adjusted incidence rate (AAIR) of HPSCC and its temporal trend during 2004-2019. Using the separate SEER 17 database, we further evaluated racial disparity in clinicopathological features, and in prognosis using Kaplan-Meier curves and Cox proportional hazard models. HPSCC accounted for 95.8% of all hypopharyngeal cancers and occurred much more frequently in males. Its incidence decreased in both male and females, in male non-Hispanic white (NHW), non-Hispanic black (NHB) and Hispanic as well as female NHW and NHB during the study period. NHB had the highest, whereas non-Hispanic Asian or Pacific Islanders (API) had comparable and the lowest incidence in both males and females. Among 6,172 HPSCC patients obtained from SEER 17 database, 80.6% were males and 83.9% were at the advanced stages III/IV. Five-year cancer specific and overall survival rates were 41.2% and 28.9%, respectively. NHB patients were more likely to be younger, unmarried, from the Southern region, larger sized tumor, and at the stage IV, but less likely to receive surgery. They also had higher proportions of dying from HPSCC and all causes. Multivariate analyses revealed that NHB with HPSCC at the locally advanced stage had both significantly worse cancer specific and overall survival compared with NHW, but not at early stage (I/II) or distant metastatic stage. Hispanic patients had significantly better prognosis than NHW at locally advanced and metastatic stages. NHW and API had comparable prognoses. HPSCC displays continuously decreased incidence and racial disparity. The majority of the disease is diagnosed at the advanced stage. NHB have the highest burden of HPSCC and a worse prognosis. More studies are needed to curtail racial disparity and improve early detection.


Imputation accuracy is robust to cattle reference genome updates.
Genotype imputation is routinely applied in a large number of cattle breeds. Imputation has become a need due to the large number of SNP arrays with variable density (currently, from 2900 to 777,962 SNPs). Although many authors have studied the effect of different statistical methods on imputation accuracy, the impact of a (likely) change in the reference genome assembly on imputation from lower to higher density has not been determined so far. In this work, 1021 Italian Simmental SNP genotypes were remapped on the three most recent reference genome assemblies. Four imputation methods were used to assess the impact of an update in the reference genome. As expected, the four methods behaved differently, with large differences in terms of accuracy. Updating SNP coordinates on the three tested cattle reference genome assemblies determined only a slight variation on imputation results within method.


Porcine encephalomyocarditis virus strain BD2 isolated from northern China is highly virulent for BALB/c mice.
Encephalomyocarditis virus (EMCV) can cause acute myocarditis in young pigs or reproductive failure in sows. The BD2 strain was isolated from the suspected piglets with EMCV in China. In order to establish an experimental animal model of EMCV, eight-weeks-old male BALB/c mice were intraperitonealy inoculated with 0.1 ml of 4×10(5) TCID50 suspension of the EMCV. Infected mice demonstrated hind limb paralysis, and movement disorder. The mortality rate of the infected group was 100% during the one-week observation period. The viral load in the brain of challenged mice gradually increased, with a peak level being 6.53 log CCID50/0.1 ml 5 days post infection. The pathological injury in infected mice was presented as neuronal necrosis. Brown positive staining could be detected in the cytoplasm of cerebral neurons. These results indicate that the porcine EMCV isolated from China could replicate in brain tissues and induce acute encephalitis in BALB/c mice.


Threat and efficacy uncertainty in news coverage about bed bugs as unique predictors of information seeking and avoidance: an extension of the EPPM.
An experiment was conducted from the perspective of the Extended Parallel Process Model (EPPM) investigating readers' responses to print news stories about the issue of bed bugs. Stories containing reference to (a) the threat of bed bugs and (b) efficacy of the solution were manipulated to vary the level of certainty with which the variables were discussed. Results suggest that stories referencing uncertainty regarding presence of the bed-bug threat may be more likely to motivate intention to seek information than stories referencing certainty of the threat. Results also suggest that stories referencing uncertainty regarding feasibility/effectiveness of proposed solutions may be more likely to motivate intention to avoid information than stories referencing certainty of proposed solutions. Given that information avoidance is one of various types of maladaptive responses to fear appeal messages (according to EPPM), results suggest that the presence of uncertainty when discussing solutions to threats in news stories might result in problematic avoidance responses that discourage people from taking protective action.


Effect of tobacco abuse on pulmonary thallium uptake during exercise myocardial perfusion scintigraphy.
To determine the influence of tobacco abuse on thallium 201 lung uptake during exercise, we examined 185 consecutive subjects with normal myocardial perfusion scans and without electrocardiographic evidence of left ventricular hypertrophy. The subjects were divided into two groups: group 1 subjects (n = 60) had histories of smoking and group 2 subjects (n = 125) were nonsmokers. Eighty-eight percent of group 1 subjects and 92% of group 2 subjects were examined using single-photon emission computed tomography and the remaining patients underwent planar imaging. 201Tl lung and heart activities were quantified from the immediate anterior planar images that were obtained in all subjects and reported as lung to heart ratio (L/H). 201Tl L/H in smokers (0.39 +/- 0.11) was significantly higher (P < 0.05) than in nonsmokers (0.34 +/- 0.06) when subjects who achieved 85% of the target heart rate were compared. In conclusion, 201Tl L/H was higher in smokers than in nonsmokers when subjects who achieved 85% of the target heart rate and had no myocardial perfusion defects were compared.


Structural basis for broad substrate specificity in higher plant beta-D-glucan glucohydrolases.
Family 3 beta-D-glucan glucohydrolases are distributed widely in higher plants. The enzymes catalyze the hydrolytic removal of beta-D-glucosyl residues from nonreducing termini of a range of beta-D-glucans and beta-D-oligoglucosides. Their broad specificity can be explained by x-ray crystallographic data obtained from a barley beta-D-glucan glucohydrolase in complex with nonhydrolyzable S-glycoside substrate analogs and by molecular modeling of enzyme/substrate complexes. The glucosyl residue that occupies binding subsite -1 is locked tightly into a fixed position through extensive hydrogen bonding with six amino acid residues near the bottom of an active site pocket. In contrast, the glucosyl residue at subsite +1 is located between two Trp residues at the entrance of the pocket, where it is constrained less tightly. The relative flexibility of binding at subsite +1, coupled with the projection of the remainder of bound substrate away from the enzyme's surface, means that the overall active site can accommodate a range of substrates with variable spatial dispositions of adjacent beta-D-glucosyl residues. The broad specificity for glycosidic linkage type enables the enzyme to perform diverse functions during plant development.


Cloning and tissue-specific expression of spliced variants of the rat organic anion transporter (rOAT-K).
During the last decade, molecular cloning has identified several families of multispecific organic ion transporters mediating the renal and hepatic elimination of organic ions. Clinically, these transporters play important roles in the renal tubular secretion and reabsorption of various drugs. They are also in part responsible for the drug pharmacologic responses, drug-drug interactions, and drug nephrotoxicity. This study describes 12 novel isoforms of the rat kidney organic anion transporter rOAT-K. These isoforms are spliced variants of the same gene arising from alternative splicing of six regions defined as A-F. The two previously reported isoforms rOAT-K1 and rOAT-K2 were also found to be spliced variants of this gene. The open reading frames of the 12 isoforms encode a range of 352-670 amino acid proteins. Tissue distribution studies showed that the majority of the isoforms are kidney- and liver-specific.


Burden of dengue, leishmaniasis and lymphatic filariasis in India and its states from 1990-2019: Analysis from the Global Burden of Disease study (GBD 2019).
Vector-borne diseases such as dengue, leishmaniasis, and lymphatic filariasis, constitute significant sources of illness, disability, and mortality among the poor and vulnerable in many countries around the world, including India. Based on the global burden of diseases, injuries, and risk factors study 2019, we analyse the burden of dengue, leishmaniasis, and lymphatic filariasis, in India from 1990 to 2019. Over this period, there was a reduction in the burden of lymphatic filariasis and leishmaniasis. Notably, dengue emerged as the most common vector-borne disease, exhibiting high fatality rate above 15 years of age and the highest DALY within 15-49 age group. Additionally, dengue cases surged substantially between 1990 and 2019. Leishmaniasis related mortality and DALY declined in the year 2019 compared to the year 1990, with high mortality and DALY in the 0-49-year-old age group. For lymphatic filariasis, DALY was more pronounce among those in the 15-49-year age group, which underwent reduction in 2019. Males had a higher burden in other vector-borne diseases than females, although females had a slightly elevated dengue burden. These findings highlight the evolving epidemiological trends related to vector-borne diseases in India, over the last three decades and underline the critical significance of sustained efforts for the elimination and control of vector-borne diseases.


Occurrence, Phenotypic and Molecular Characterization of Extended-Spectrum- and AmpC- β-Lactamase Producing Enterobacteriaceae Isolated From Selected Commercial Spinach Supply Chains in South Africa.
The increasing occurrence of multidrug-resistant (MDR) extended-spectrum β-lactamase- (ESBL) and/or AmpC β-lactamase-producing Enterobacteriaceae in health care systems, the environment and fresh produce is a serious concern globally. Production practices, processing and subsequent consumption of contaminated raw fruit and vegetables represent a possible human transmission route. The purpose of this study was to determine the presence of ESBL/AmpC-producing Enterobacteriaceae in complete spinach supply chains and to characterize the isolated strains phenotypically (antimicrobial resistance profiles) and genotypically (ESBL/AmpC genetic determinants, detection of class 1, 2, and 3 integrons). Water, soil, fresh produce, and contact surface samples (n = 288) from two commercial spinach production systems were screened for ESBL/AmpC-producing Enterobacteriaceae. In total, 14.58% (42/288) of the samples were found to be contaminated after selective enrichment, plating onto chromogenic media and matrix-assisted laser desorption ionization time-of-flight mass spectrometry identity confirmation of presumptive ESBL/AmpC isolates. This included 15.28% (11/72) water and 12.12% (16/132) harvested- and processed spinach, while 25% (15/60) retail spinach samples were found to be contaminated with an increase in isolate abundance and diversity in both scenarios. Dominant species identified included Serratia fonticola (45.86%), Escherichia coli (20.83%), and Klebsiella pneumoniae (18.75%). In total, 48 (81.36%) isolates were phenotypically confirmed as ESBL/AmpC-producing Enterobacteriaceae of which 98% showed a MDR phenotype. Genotypic characterization (PCR of ESBL/AmpC resistance genes and integrons) further revealed the domination of the CTX-M Group 1 ESBL type, followed by TEM and SHV; whilst the CIT-type was the only plasmid-mediated AmpC genetic determinant detected. Integrons were detected in 79.17% (n = 38) of the confirmed ESBL/AmpC-producing isolates, of which we highlight the high prevalence of class 3 integrons, detected in 72.92% (n = 35) of the isolates, mostly in S. fonticola. Class 2 integrons were not detected in this study. This is the first report on the prevalence of ESBL/AmpC-producing Enterobacteriaceae isolated throughout commercial spinach production systems harboring class 1 and/or class 3 integrons in Gauteng Province, South Africa. The results add to the global knowledge base regarding the prevalence and characteristics of ESBL/AmpC-producing Enterobacteriaceae in fresh vegetables and the agricultural environment required for future risk analysis.


The Clinical Significance of PIWIL3 and PIWIL4 Expression in Pancreatic Cancer.
P-element-induced wimpy testis (PIWI) proteins have been described in several cancers. PIWIL1 and PIWIL2 have been recently evaluated in pancreatic cancer, and elevated expression of PIWIL2 conferred longer survival to patients. However, PIWIL3's and PIWIL4's role in carcinogenesis is rather controversial, and their clinical implication in pancreatic cancer has not yet been investigated. In the present study, we evaluated PIWIL1, PIWIL2, PIWIL3 and PIWIL4 expression in pancreatic cancer-derived cell lines and in one non-tumor cell line as healthy control. Here, we show a differential expression in tumor and non-tumor cell lines of PIWIL3 and PIWIL4. Subsequently, functional experiments with PIWIL3 and/or PIWIL4 knockdown revealed a decrease in the motility ratio of tumor and non-tumor cell lines through downregulation of mesenchymal factors in pro of epithelial factors. We also observed that PIWIL3 and/or PIWIL4 silencing impaired undifferentiated phenotype and enhanced drug toxicity in both tumor- and non-tumor-derived cell lines. Finally, PIWIL3 and PIWIL4 evaluation in human pancreatic cancer samples showed that patients with low levels of PIWIL4 protein expression presented poor prognosis. Therefore, PIWIL3 and PIWIL4 proteins may play crucial roles to keep pancreatic cell homeostasis not only in tumors but also in healthy tissues.


The Influence of Face Shields on the Quality of Colonoscopy in the Era of the COVID-19 Pandemic.
The worldwide coronavirus disease 2019 pandemic has led endoscopists to use personal protective equipment (PPE) for infection prevention. This study aimed to investigate whether wearing a face shield as PPE affects the quality of colonoscopy. We reviewed the medical records and colonoscopy findings of patients who underwent colonoscopies at Asan Medical Center, Korea from March 10 to May 31, 2020. The colonoscopies in this study were performed by five gastroenterology fellows and four expert endoscopists. We compared colonoscopy quality indicators, such as withdrawal time, adenoma detection rate (ADR), mean number of adenomas per colonoscopy (APC), polypectomy time, and polypectomy adverse events, both before and after face shields were added as PPE on April 13, 2020. Of the 1,344 colonoscopies analyzed, 715 and 629 were performed before and after the introduction of face shields, respectively. The median withdrawal time was similar between the face shield and no-face shield groups (8.72 minutes vs 8.68 minutes, p=0.816), as was the ADR (41.5% vs 39.8%, p=0.605) and APC (0.72 vs 0.77, p=0.510). Polypectomy-associated quality indicators, such as polypectomy time and polypectomy adverse events were also not different between the groups. Quality indicators were not different between the face shield and no-face shield groups of gastroenterology fellows, or of expert endoscopists. Colonoscopy performance was not unfavorably affected by the use of a face shield. PPE, including face shields, can be recommended without a concern about colonoscopy quality deterioration.