Unequal airborne exposure to toxic metals associated with race, ethnicity, and segregation in the USA.
Persons of color have been exposed to a disproportionate burden of air pollution across the United States for decades. Yet, the inequality in exposure to known toxic elements of air pollution is unclear. Here, we find that populations living in racially segregated communities are exposed to a form of fine particulate matter with over three times higher mass proportions of known toxic and carcinogenic metals. While concentrations of total fine particulate matter are two times higher in racially segregated communities, concentrations of metals from anthropogenic sources are nearly ten times higher. Populations living in racially segregated communities have been disproportionately exposed to these environmental stressors throughout the past decade. We find evidence, however, that these disproportionate exposures may be abated though targeted regulatory action. For example, recent regulations on marine fuel oil not only reduced vanadium concentrations in coastal cities, but also sharply lessened differences in vanadium exposure by segregation.


Air pollution and mortality in Madrid, Spain: a time-series analysis.
To assess the relationship, if any, between air pollutant (sulfur dioxide and total suspended particulate) levels and mortality in the city of Madrid during the period 1986-1992, controlling for weather, season, and influenza epidemics. Daily death counts were obtained from the Regional Mortality Registry. Pollution data were supplied by the Municipal Monitoring Network. Time-series analysis methodology was used to assess the link between non-accidental as well as circulatory- and respiratory-disease mortality, on the one hand, and mean daily concentrations of SO2 and total suspended particulate (TSP), on the other. Multivariate autoregressive integrated moving-average (ARIMA) models were used to adjust for season, temperature, relative humidity, and influenza. A sensitivity analysis was run to assess the robustness of the estimators. Graphical analysis revealed a linear relationship between mortality and TSP. The relationship was logarithmic in the case of SO2. TSP lagged 1 day and SO2 lagged 3 days with an independent effect on mortality. This relationship was produced without the detection of a minimal threshold in emission values. These results support the hypothesis of an association between pollution levels and mortality between 1986-1992 in Madrid. Additional measures designed to reduce pollution levels without compromising thermal comfort should be implemented.


Generation of iPSC line FAMRCi010-A from patient with restrictive cardiomyopathy carrying genetic variant FLNC p.Gly2011Arg.
Human iPSC cell line FAMRCi010-A was generated from a patient with restrictive cardiomyopathy carrying FLNC p.Gly2011Arg genetic variant. Patient-specific peripheral blood mononuclear cells were reprogrammed using non-integrative Sendai viruses containing OCT4, SOX2, KLF4, and CMYC. FAMRCi010-A was generated and characterized through the study. The reported iPSC line could be useful tool for in vitro modeling of FLNC-associated cardiomyopathies.


Ultrasound assisted cold gelation of kappa carrageenan dispersions.
Usually to prepare a gel from kappa carrageenan, an aqueous dispersion of carrageenan powder is heated. This research presents evidence of cold gelation of carrageenan dispersions while no heat is needed. The occurrence of cold gelation is investigated in the absence or presence of potassium ions during ultrasound treatment by studying the mechanical and microstructural properties of the prepared gels using a texture analyzer and scanning electron microscopy, respectively. Carrageenan gels were obtained by applying power ultrasound. By increasing sonication time, gel hardness increased up to a certain level (in absence or presence of K(+) during ultrasound treatment) and further ultrasound application had a negative effect. Moreover, the mechanical properties of the gels in which K(+) ions were added before ultrasound were weaker than the samples when K(+) ions were added after sonication. Relaxation times of gels were calculated using the generalized Maxwell model with three elements.


A tissue specific approach for analysis of membrane and secreted protein antigens from Haemonchus contortus gut and its application to diverse nematode species.
General methods to conduct tissue specific analysis are largely lacking for nematodes. An approach is described that focused on isolation of membrane and secreted protein genes from the gut of the parasitic nematode Haemonchus contortus. The approach capitalized on a monoclonal antibody that recognizes multiple membrane and secreted worm proteins. Polyclonal antisera made against these proteins were used to screen expression cDNA libraries made either from adult worm gut or whole worm. The genes identified encode predicted or known membrane and secreted proteins from gut, including a cysteine protease, a zinc metallopeptidase and a previously described GA1 protein. Another gene, Hc40, was isolated from the whole worm cDNA library and is nearly identical to a vaccine patent sequence pBTA879. Tissue analysis demonstrated the intended focus on membrane and secreted proteins from parasite gut was achieved. Proteins related to each of those described were identified from other nematode species through data base analysis. Additionally, this analysis led to (1) identification of homologues of each gene in C. elegans; (2) deduction of a dimorphic structure in the Hc40 protein; (3) recognition of both monomorphic and dimorphic families of Hc40-related proteins; and (4) detection of two apparent classes of transcripts (mep1a and mep1b) that would each encode a divergent version of the putative zinc metallopeptidase MEP1. The tissue specific approach and information base described should generally contribute to investigations on nutrient digestion and related secretory processes in nematode gut.


Motor vehicle fatalities increase just after publicized suicide stories.
The average increase in motor vehicle fatalities is 9.12 percent in the week after a suicide story. The more publicity given to the story, the greater the rise in motor vehicle deaths thereafter. This rise apparently occurs because suicide stories stimulate a wave of imitative suicides, some of which are disguised as motor vehicle accidents.


Induced expression and localization to nuclear-inclusion bodies of hsp70 in varicella-zoster virus-infected human diploid fibroblasts.
The expression and subcellular localization of cellular heat-shock protein hsp70 were examined in varicella-zoster virus (VZV)-infected human diploid fibroblasts. Infection with VZV elevated the steady-state levels of hsp70 mRNA by 24 hr post-infection (hpi). Western blotting analysis revealed an increase in accumulation of hsp70 from 24 hpi. Subcellular localization of the hsp70 in VZV-infected cells was examined by indirect immunofluorescence. In most VZV-infected cells, hsp70 was localized to inclusion bodies induced in the cell nucleus by infection with VZV. In some cells, however, the remaining parts of the cell nucleus and the cytoplasm were also stained with anti-hsp70 antibody. These results indicate that infection with VZV induces the expression of hsp70 and its localization to VZV-specific inclusion bodies, which suggests the involvement of hsp70 in molecular events within inclusion bodies.


Anesthetic sevoflurane simultaneously regulates autophagic flux and pyroptotic cell death-associated cellular inflammation in the hypoxic/re-oxygenated cardiomyocytes: Identification of sevoflurane as putative drug for the treatment of myocardial ischemia-reperfusion injury.
PRE: and post-conditioning of sevoflurane attenuate cardiomyocyte death and protects against myocardial ischemia/reperfusion (I/R) injury, and this process is considered to be associated with cell autophagy and pyroptosis, but the detailed molecular mechanisms regarding to this issue have not been fully studied. In this study, we verified that sevoflurane exerted its protective effects in myocardial I/R injury by synergistically regulating the AMPK/ULK1 pathway-mediated autophagy and NLRP3-mediated pyroptotic cell death, and the interplays between cell autophagy and pyroptosis were also preliminarily investigated. Specifically, sevoflurane conditioning suppressed NLRP3 and cleaved caspase-1 expressions to inactivate cell pyroptosis, upregulated LC3B-II/I ratio, facilitated autophagosome formation and accelerated p62 degradation to trigger autophagy, and promoted the expressions of CDK2, CDK6 and Cyclin D1 to recover cell cycle in I/R mouse myocardial tissues in vivo and hypoxic/re-oxygenated (H/R) cardiomyocytes in vitro. Further experiments validated that sevoflurane promoted the phosphorylation of both AMPK (p-AMPK) and ULK1 (p-ULK1) to activate the AMPK/ULK1 pathway, and the promoting effects of sevoflurane on cell autophagy in H/R cardiomyocytes were abrogated by co-treating cells with AMPK inhibitor (compound C) and ULK1 inhibitor (SBI-0206965). Moreover, it was verified that compound C, SBI-0206965 and autophagy blocker chloroquine reversed H/R-induced cell death and pyroptosis in cardiomyocytes. Taken together, we concluded that sevoflurane activated the AMPK/ULK1 pathway to trigger autophagic flux and suppress NLRP3-mediated pyroptotic cell death in I/R or H/R-treated cardiomyocytes, which further ameliorated myocardial I/R injury.


Multispecies autocatalytic RNA reaction networks in coacervates.
Robust localization of self-reproducing autocatalytic chemistries is a key step in the realization of heritable and evolvable chemical systems. While autocatalytic chemical reaction networks already possess attributes such as heritable self-reproduction and evolvability, localizing functional multispecies networks within complex primitive phases, such as coacervates, has remained unexplored. Here, we show the self-reproduction of the Azoarcus ribozyme system within charge-rich coacervates where catalytic ribozymes are produced by the autocatalytic assembly of constituent smaller RNA fragments. We systematically demonstrate the catalytic assembly of active ribozymes within phase-separated coacervates-both in micron-sized droplets as well as in a coalesced macrophase, underscoring the facility of the complex, charge-rich phase to support these reactions in multiple configurations. By constructing multispecies reaction networks, we show that these newly assembled molecules are active, participating both in self- and cross-catalysis within the coacervates. Finally, due to differential molecular transport, these phase-separated compartments endow robustness to the composition of the collectively autocatalytic networks against external perturbations. Altogether, our results establish the formation of multispecies self-reproducing reaction networks in phase-separated compartments which in turn render transient robustness to the network composition.


[Effect of nitric oxide upon apoptosis activation in immunocompetent blood cells in diabetes mellitus, type 1].
NO-synthase activity, the content of stable products of NO metabolism (nitrites and nitrates) as well as fragmented DNA as biochemical marker of apoptosis have been determined in segmentonuclear neutrophilic granulocytes and mononuclear leukocytes in blood of healthy donors and patients with type 1 diabetes mellitus. It was found that activation of apoptosis in polymorphonuclear and mononuclear blood leukocytes under diabetes mellitus was accompanied by an elevation of NO-synthase activity and the content of stable NO metabolites. This suggests an increase of proapoptotic action of nitric oxide in immunocompetent blood cells under the pathology studied.


A Radiological Nomogram to Predict 30-day Mortality in Patients with Acute Pulmonary Embolism.
Acute pulmonary embolism (APE) is a common disease with a high mortality, especially in the short term. Computed tomographic pulmonary angiography (CTPA) is a recommended method in the diagnostic workup for APE; thus, this study aimed to establish a CTPA-based radiological nomogram to predict the 30-day mortality in patients with APE, and to further compare this model with the pulmonary embolism severity index (PESI) and simplified pulmonary embolism severity index (SPESI). We retrospectively recruited 158 adults with confirmed APE who underwent CTPA from August 1, 2017, to August 1, 2020. These adults were stratified into two groups according to their 30-day mortality. CTPA-based variables were analyzed using univariate and multivariate analyses, independent risk factors for 30-day mortality were established, and a radiological nomogram was constructed. Subsequently, PESI and SPESI were calculated. The performance of the radiological nomogram model was compared to that of the PESI and SPESI using decision curve analysis and receiver-operating characteristic curve analysis. Thirty-three patients died within 30 days (30-day mortality rate, 20.9%). On logistic regression analysis, the right and left ventricular diameter ratio (odds ratio [OR] = 8.709, 95% confidence interval [CI]: 1.085-69.903, p = 0.042), ventricular septal bowing (OR = 8.085, 95% CI: 1.947-33.567, p = 0.004), chronic bronchitis (OR = 4.383, 95% CI: 1.025-18.740, p = 0.046), malignant lung lesions (OR = 17.530, 95% CI: 2.408-127.636, p = 0.005), and pneumonia (OR = 3.477, 95% CI: 1.123-10.766, p = 0.031) were identified as the independent predictors of 30-day mortality. The area under the curve of the radiological nomogram, PESI, and SPESI were 0.900 (95% CI: 0.828-0.971), 0.729 (95% CI: 0.642-0.815), and 0.718 (95% CI: 0.621-0.815), respectively. The CTPA-based radiological nomogram appeared valuable for the prediction of 30-day mortality in patients with APE, and was superior to both PESI and SPESI.


Sympatho-adrenal involvement in methamphetamine-induced hyperthermia through skeletal muscle hypermetabolism.
We investigated the involvement of the sympatho-adrenal axis in the hyperthermia induced by methamphetamine by using a biotelemetric system. The intraperitoneal injection of methamphetamine (1 mg/kg) induced hyperthermia preceded by an increase in oxygen consumption in freely moving rats. The hyperthermic effect of methamphetamine was completely blocked by chemical sympathectomy with 6-hydroxydopamine (50 mg/kg, i.p.). Adrenalectomy, but not adrenal demedullation, prevented the hyperthermia. In adrenalectomized rats, dexamethasone supplementation (0.5 mg/kg, s.c.) restored the methamphetamine-induced hyperthermia. Furthermore, dantrolene (1 or 2 mg/kg, i.v.), which blocks Ca2+ release from the sarcoplasmic reticulum in skeletal muscle, attenuated the hyperthermia. These results suggest that methamphetamine stimulates norepinephrine release from sympathetic nerve terminals, which then enhances thermogenesis in skeletal muscle under the permissive action of glucocorticoids.


Nanocrystalline cellulose extraction process and utilization of the byproduct for biofuels production.
Cellulose consists of amorphous and crystalline regions. It is the crystalline regions which may be exploited to produce nanocrystalline cellulose (NCC). In order to extract nanocrystalline cellulose from native cellulose, sulfuric acid hydrolysis is typically used. The amorphous regions of cellulose are hydrolyzed and degraded into soluble products while the crystalline regions remain intact. In an effort to make the NCC extraction process more feasible, a new process was developed to recover and utilize the hydrolyzed regions of cellulose as a byproduct. The acid hydrolyzed amorphous regions were separated and then recovered (regenerated) into solid particles. XRD data revealed that the recovered material is characteristic of cellulose II. Hydrolysis conditions were optimized to maximize the yield of the recovered material and at the same time produce NCC material. Preliminary experiments showed yield values of approximately 61% for the cellulose I crystalline portions and values of about 21.7% for the recovered material (cellulose II). Enzymatic hydrolysis experiments of the recovered material revealed high susceptibility to enzymatic hydrolysis which makes it a promising source for biofuels production.


Association of four health behaviors in Life's Essential 8 with the incidence of hypertension and diabetes mellitus.
The association between health behaviors and the risk of developing hypertension and diabetes is not fully understood. We aimed to examine the association between four health behaviors involved in Life's Essential 8, the American Heart Association's key measures for improving and maintaining cardiovascular health, and the incidence of hypertension and diabetes. This observational cohort study used the JMDC Claims Database between 2005 and 2021, which is a health check-up and claims database. We analyzed 2,912,183 participants without a history of hypertension, diabetes, cardiovascular disease, or renal failure. Non-ideal health behaviors included smoking, slow gait speed, eating fast, and poor sleep quality. During 1140 ± 877 days, 201,385 hypertension and 142,156 diabetes events were recorded. In a multivariable Cox regression analysis, the risk of hypertension and diabetes increased with an increasing number of non-ideal health behaviors. The hazard ratios (HRs) (95% confidence interval [CI]) per 1-point increase in non-ideal health behavior components for hypertension and diabetes were 1.11 (1.10-1.11) and 1.08 (1.08-1.09), respectively. Each health behavior was independently associated with the incidence of hypertension and diabetes. A 1-point improvement in health behaviors was associated with a lower risk of developing hypertension (HR 0.94, 95% CI 0.93-0.95) and diabetes (HR 0.95, 95% CI 0.94-0.96). Factors that can be substituted for the four health behaviors involved in Life's Essential 8 can stratify the risk of hypertension and diabetes, and improving these health behaviors is useful in preventing hypertension and diabetes in general population.


The Association Between Physical Activity, Including Physical Activity Intensity, and Fear of Falling Differs by Fear Severity in Older Adults Living in the Community.
Fear of falling (FoF) is common in older adults. Physical activity decreases as FoF increases. However, this association between physical activity and FoF may vary depending on activity intensity. The current study was performed to explore the associations between FoF and step count, light-intensity physical activity (LPA), and moderate/vigorous-intensity physical activity (MVPA) in community-dwelling older adults. This cross-sectional observational study was held at a local community association center, with 242 older adults living independently in the community (mean age: 75.1 ± 5.4 years). FoF was defined using the Falls Efficacy Scale-International and categorized into three levels (low, moderate, and high). Physical activity was measured using a uniaxial accelerometer worn for 7 consecutive days, and by calculating daily step count, LPA, and MVPA, over this period. Step count and physical activity intensity showed significant linear trends across FoF severity (p < .01, respectively). High FoF decreased step count by approximately 2,000 steps/day. Further, high FoF was significantly associated with short durations of both LPA and MVPA. In addition, moderate FoF was associated with decreased LPA duration, even after adjustment for confounding variables. Physical activity decreased concomitantly with a rise in FoF severity. Moreover, the association between physical activity and FoF differed by physical activity intensity level in community-dwelling older adults. Further studies are needed to investigate the causal relationship between FoF and objective physical activity in this population.


Prevalence, correlates, and comorbidity of DSM-IV obsessive-compulsive personality disorder: results from the National Epidemiologic Survey on Alcohol and Related Conditions.
Although recognized for over 100 years, there is a relative dearth of empirical research on obsessive compulsive personality disorder (OCPD). The goal of the current study is to present nationally representative findings on prevalence, sociodemographic correlates, and comorbidity of OCPD among men and women. The current study uses nationally representative data to examine sociodemographic correlates and comorbidity of OCPD. Face-to-face interviews were conducted with 43,093 adults in the United States. The prevalence of lifetime OCPD was 7.8%, with rates the same for men and women. OCPD was significantly less common in younger adults and in Asians and Hispanics but was significantly more common in individuals with a high school education or less. When sociodemographic variables and other comorbidities were controlled for, current associations remained significant for all mood and anxiety disorders as well as lifetime personality disorders among both men and women. OCPD is a prevalent personality disorder in the US population and is equally represented in men and women. The results highlight the need for further research to identify common pathophysiological elements common to OCPD and associated disorders.


Tetramic and tetronic acids: an update on new derivatives and biological aspects.
Significant developments in the isolation of tetramic acids and tetronic acids, in the elucidation of their biosyntheses and their biological activities and in laboratory syntheses are reviewed with a focus on those derivatives with medicinal and pharmacological relevance. Important new members of the title compound families isolated since the year 2000 are covered as well as new biological aspects of some earlier congeners.


Interactions between Invasive Monk Parakeets (Myiopsitta monachus) and Other Bird Species during Nesting Seasons in Santiago, Chile.
The monk parakeet (Myiopsitta monachus) is considered to be one of the most invasive bird species because its unique ability among parrots to build their own communal nests. Currently, they are considered an invasive species in 19 countries and a pest-even in their native distribution-because of economic losses derived from their impacts. During the reproductive seasons of 2017 and 2018, we registered interactions between invasive monk parakeets and resident bird species in Santiago, Chile. We observed agonistic and affiliative interactions, and further, we described monk parakeets' nest occupancy by nine bird species, two invasive and seven native. For this reason, we consider that the monk parakeet is an allogenic ecosystem engineer with the potential to shape distribution and richness of sympatric species in urban environments. Our results contribute to an assessment of the implications of the monk parakeet's ecological invasion to other synanthropic species, and raise concern of other potential impacts, such as pathogen transmission derived from these interactions.


[Fabrication of acrylic teeth for children's dentures].
A simple technique to make children's prosthatic teeth with possibility of many sizes and form, stable shades, hard structure and fast work.


Characterization of a strain-specific CD-1 reference genome reveals potential inter- and intra-strain functional variability.
CD-1 is an outbred mouse stock that is frequently used in toxicology, pharmacology, and fundamental biomedical research. Although inbred strains are typically better suited for such studies due to minimal genetic variability, outbred stocks confer practical advantages over inbred strains, such as improved breeding performance and low cost. Knowledge of the full genetic variability of CD-1 would make it more useful in toxicology, pharmacology, and fundamental biomedical research. We performed deep genomic DNA sequencing of CD-1 mice and used the data to identify genome-wide SNPs, indels, and germline transposable elements relative to the mm10 reference genome. We used multiple genome-wide sequencing data types and previously published CD-1 SNPs to validate our called variants. We used the called variants to construct a strain-specific CD-1 reference genome, which we show can improve mappability and reduce experimental biases from genome-wide sequencing data derived from CD-1 mice. Based on previously published ChIP-seq and ATAC-seq data, we find evidence that genetic variation between CD-1 mice can lead to alterations in transcription factor binding. We also identified a number of variants in the coding region of genes which could have effects on translation of genes. We have identified millions of previously unidentified CD-1 variants with the potential to confound studies involving CD-1. We used the identified variants to construct a CD-1-specific reference genome, which can improve accuracy and reduce bias when aligning genomics data derived from CD-1 mice.


Mechanisms of action of therapeutic exercise for knee and hip OA remain a black box phenomenon: an individual patient data mediation study with the OA Trial Bank.
To evaluate mediating factors for the effect of therapeutic exercise on pain and physical function in people with knee/hip osteoarthritis (OA). For Subgrouping and TargetEd Exercise pRogrammes for knee and hip OsteoArthritis (STEER OA), individual participant data (IPD) were sought from all published randomised controlled trials (RCTs) comparing therapeutic exercise to non-exercise controls in people with knee/hip OA. Using the Counterfactual framework, the effect of the exercise intervention and the percentage mediated through each potential mediator (muscle strength, proprioception and range of motion (ROM)) for knee OA and muscle strength for hip OA were determined. Data from 12 of 31 RCTs of STEER OA (1407 participants) were available. Within the IPD data sets, there were generally statistically significant effects from therapeutic exercise for pain and physical function in comparison to non-exercise controls. Of all potential mediators, only the change in knee extension strength was statistically and significantly associated with the change in pain in knee OA (β -0.03 (95% CI -0.05 to -0.01), 2.3% mediated) and with physical function in knee OA (β -0.02 (95% CI -0.04 to -0.00), 2.0% mediated) and hip OA (β -0.03 (95% CI -0.07 to -0.00), no mediation). This first IPD mediation analysis of this scale revealed that in people with knee OA, knee extension strength only mediated ±2% of the effect of therapeutic exercise on pain and physical function. ROM and proprioception did not mediate changes in outcomes, nor did knee extension strength in people with hip OA. As 98% of the effectiveness of therapeutic exercise compared with non-exercise controls remains unexplained, more needs to be done to understand the underlying mechanisms of actions.


Can Cross-Country Genomic Predictions Be a Reasonable Strategy to Support Germplasm Exchange? - A Case Study With Hydrogen Cyanide in Cassava.
Genomic prediction (GP) offers great opportunities for accelerated genetic gains by optimizing the breeding pipeline. One of the key factors to be considered is how the training populations (TP) are composed in terms of genetic improvement, kinship/origin, and their impacts on GP. Hydrogen cyanide content (HCN) is a determinant trait to guide cassava's products usage and processing. This work aimed to achieve the following objectives: (i) evaluate the feasibility of using cross-country (CC) GP between germplasm's of Embrapa Mandioca e Fruticultura (Embrapa, Brazil) and The International Institute of Tropical Agriculture (IITA, Nigeria) for HCN; (ii) provide an assessment of population structure for the joint dataset; (iii) estimate the genetic parameters based on single nucleotide polymorphisms (SNPs) and a haplotype-approach. Datasets of HCN from Embrapa and IITA breeding programs were analyzed, separately and jointly, with 1,230, 590, and 1,820 clones, respectively. After quality control, ∼14K SNPs were used for GP. The genomic estimated breeding values (GEBVs) were predicted based on SNP effects from analyses with TP composed of the following: (i) Embrapa genotypic and phenotypic data, (ii) IITA genotypic and phenotypic data, and (iii) the joint datasets. Comparisons on GEBVs' estimation were made considering the hypothetical situation of not having the phenotypic characterization for a set of clones for a certain research institute/country and might need to use the markers' effects that were trained with data from other research institutes/country's germplasm to estimate their clones' GEBV. Fixation index (FST) among the genetic groups identified within the joint dataset ranged from 0.002 to 0.091. The joint dataset provided an improved accuracy (0.8-0.85) compared to the prediction accuracy of either germplasm's sources individually (0.51-0.67). CC GP proved to have potential use under the present study's scenario, the correlation between GEBVs predicted with TP from Embrapa and IITA was 0.55 for Embrapa's germplasm, whereas for IITA's it was 0.1. This seems to be among the first attempts to evaluate the CC GP in plants. As such, a lot of useful new information was provided on the subject, which can guide new research on this very important and emerging field.


A functional neural network computing some eigenvalues and eigenvectors of a special real matrix.
How to quickly compute eigenvalues and eigenvectors of a matrix, especially, a general real matrix, is significant in engineering. Since neural network runs in asynchronous and concurrent manner, and can achieve high rapidity, this paper designs a concise functional neural network (FNN) to extract some eigenvalues and eigenvectors of a special real matrix. After equivalent transforming the FNN into a complex differential equation and obtaining the analytic solution, the convergence properties of the FNN are analyzed. If the eigenvalue whose imaginary part is nonzero and the largest of all eigenvalues is unique, the FNN will converge to the eigenvector corresponding to this special eigenvalue with general nonzero initial vector. If all eigenvalues are real numbers or there are more than one eigenvalue whose imaginary part equals the largest, the FNN will converge to zero point or fall into a cycle procedure. Comparing with other neural networks designed for the same domain, the restriction to matrix is very slack. At last, three examples are employed to illustrate the performance of the FNN.


Applying Grading of Recommendations Assessment, Development and Evaluation (GRADE) to diagnostic tests was challenging but doable.
The Grading of Recommendations Assessment, Development and Evaluation (GRADE) Working Group developed an approach to assess the quality of evidence of diagnostic tests. Its use in Cochrane diagnostic test accuracy reviews is new. We applied this approach to three Cochrane reviews with the aim of better understanding the application of the GRADE criteria to such reviews. We selected reviews to achieve clinical and methodological diversities. At least three assessors independently assessed each review according to the GRADE criteria of risk of bias, indirectness, imprecision, inconsistency, and publication bias. Two teleconferences were held to share experiences. For the interpretation of the GRADE criteria, it made a difference whether assessors looked at the evidence from a patient-important outcome perspective or from a test accuracy standpoint. GRADE criteria such as inconsistency, imprecision, and publication bias were challenging to apply as was the assessment of comparative test accuracy reviews. The perspective from which evidence is graded can influence judgments about quality. Guidance on application of GRADE to comparative test reviews and on the GRADE criteria of inconsistency, imprecision, and publication bias will facilitate the operationalization of GRADE for diagnostics.


Massive open online course adoption amongst newly graduated health care providers.
Massive Open Online Courses (MOOCs) are flexible offerings that deliver content to a large audience in a virtual platform. MOOCs are increasingly accessed by health professionals to support their own professional development. Despite the agreed usefulness of MOOCs, the rates of adoption are still extremely low. This study sought to understand the personal and social factors associated with MOOC adoption. Participants were newly graduated occupational therapists who registered for a leadership skills development MOOC. Qualitative interviews were conducted to understand unique perspectives of participants who did and did not complete the MOOC. Data were analyzed using the Unified Theory of Acceptance and Use of Technology (UTAUT) framework. Participants reported they found the MOOC content beneficial in providing a foundational framework on which to develop their leadership skills. Even though MOOC content was organized into multiple small components, participants shared that they would engage with the material once a week for up to two hours. Participants reported a high level of comfort accessing the technology to complete the MOOC, however they reported that they would have preferred more interactive or synchronous learning opportunities. MOOCs are an efficient way to offer a wide variety of educational offerings to health professionals. Despite their asynchronous nature, MOOC developers should consider maximizing opportunities for learner interaction and content application learning opportunities within MOOCs to increase their overall adoption.


Mutations in the most divergent α-tubulin isotype, α8-tubulin, cause defective platelet biogenesis.
In the panel of genes commonly associated with inherited macrothrombocytopenia, an important fraction encodes key cytoskeletal proteins such as tubulin isotypes, the building blocks of microtubules. Macrothrombocytopenia-causing mutations have been identified in the TUBB1 and TUBA4A genes, emphasizing their importance in the formation of platelets and their marginal band, a unique microtubule ring-like structure that supports the platelet typical disc-shaped morphology. This raised the hypothesis that other tubulin isotypes normally expressed in platelets could play a similar role in their formation. To assess whether tubulin isotype genes other than TUBA4A and TUBB1 could be implicated in inherited macrothrombocytopenia. We used high throughput sequencing to screen a cohort of 448 French blood donors with mild thrombocytopenia for mutations in a panel of selected genes known or suspected to be involved in platelet biogenesis. We identified six distinct novel mutations in TUBA8, which encodes the most-divergent α-tubulin, as the causative determinant of macrothrombocytopenia and platelet marginal band defects. Functionally, all TUBA8 mutations were found to fully or partially inhibit the incorporation of the mutated α8-tubulin in the microtubule network. This study provides strong support for a key role of multiple tubulin genes in platelet biogenesis by discovering variants in a tubulin gene that was previously not known to be important for platelets.


Homer isoforms differentially regulate cocaine-induced neuroplasticity.
Homer proteins modulate neuroplasticity in excitatory synapses and are dynamically regulated by cocaine. Whereas acute cocaine elevates immediate-early gene (short) isoforms of Homer1 in the nucleus accumbens, withdrawal from repeated cocaine administration downregulates the expression of constitutive Homer1 isoforms. The present study determined whether or not this downregulation in constitutive Homer expression in the accumbens is necessary for enduring alterations in cocaine-induced changes in the brain and behavior. The long vs short Homer isoforms were overexpressed in the rat nucleus accumbens during drug abstinence, and the adaptations elicited by repeated cocaine on glutamate transmission and motor behavior were measured. It was found that both chronic and acute overexpression of constitutive, but not short, Homer isoforms abolished cocaine-induced sensitization of locomotor hyperactivity and prevented the development of glutamate abnormalities in the accumbens, including the reduction in basal extracellular glutamate content and the sensitized glutamate response to a subsequent cocaine challenge injection. Together, these data indicate that the enduring reduction of long Homer isoforms in the nucleus accumbens of cocaine-withdrawn rats is necessary for the expression of cocaine-induced neuroplasticity.


Artificial beta-cell application in two cases of insulinoma: a different pattern in beta-cell adenoma and carcinoma.
With the aid of an artificial beta-cell (Biostator, Miles Laboratories Inc.), a different metabolic and biological pattern of behaviour was observed in benign versus malignant insulinoma. In the patient with beta-cell adenoma but not in the one with carcinoma, plasma insulin concentrations decreased promptly and markedly, and blood glucose increased during diazoxide and somatostatin infusion. Moreover, only in the adenoma patient was glucose need characterized by a circadian rhythm with the maximum values during daytime. This behavior could reflect the degree of tumor beta-cell differentiation. The controlled glucose and insulin infusion was of great help during and after surgical treatment.


Benign Pneumatosis Intestinalis: A Case Report and Review of the Literature.
Pneumatosis intestinalis is the presence of gas within the walls of the intestine on imaging and has variable clinical significance, ranging from an incidental finding to a harbinger of intra-abdominal catastrophe. There are multiple mechanisms by which this radiographic finding develops, including bacterial gas production, increased intraluminal pressure within the gastrointestinal tract, mechanical disruption of the gut mucosa, and tracking of pulmonary gas along the mesenteric vasculature. We present the case of a 61-year-old male veteran who had sustained a remote anoxic brain injury resulting in chronic dependence on a gastrostomy tube for enteral nutrition, found incidentally to have pneumatosis intestinalis without signs of intra-abdominal catastrophe. Appropriate interpretation of this finding can lead to life-saving interventions and avoid unnecessary surgical procedures.


Reduction of somatosensory evoked fields in the primary somatosensory cortex in a one-back task.
In the present study, responses of the somatosensory cortex to sensory input of ten human volunteers were investigated during a one-back task with different conditions of attention. During an condition of attention subjects were requested to detect a predefined sequence of tactile stimuli applied to two different fingers of the dominant hand while a series of visual stimuli was presented simultaneously with an asynchronous stimulus-onset to the tactile stimuli. During an condition of distraction subjects received the identical series of visual and tactile stimuli like in the condition of attention but were now requested to detect a predefined stimulus sequence within the visual stimulus domain. In both conditions, somatosensory evoked magnetic fields (SEFs) to the tactile stimuli were recorded by means of a 31-channel magnetoencephalograph (MEG) from subjects' contralateral primary somatosensory cortex. The mean global field power, the dipole strength, the maximum current density, and the first component of the singular value decomposition (SVD) of magnetic fields were used to compare early components of the SEF in the conditions of attention versus distraction. Surprisingly, results revealed significant decreases of measures of all four parameters during the condition of attention as compared to the condition of distraction indicating that early responses of the primary somatosensory cortex became significantly reduced in the condition of attention. We hypothesize that changes in the centre-periphery-relationship of receptive fields in the primary somatosensory cortex may account for this unexpected result.


[Problems and advantages of autopsy in the case of out-of-hospital childhood death: report of 2 cases].
In France, the number of deaths remains high in the pediatric population. These deaths are rarely subject to a scientific or forensic autopsy. However, this medical act appears necessary to answer the many private and public questions (public health, prevention, judicial, or even institutional) that can arise. Two pediatric clinical observations raising these questions in the context of a household accident are presented. In the first one, the death led to the establishment of a forensic obstacle to the burial and a forensic autopsy. The autopsy results provided answers, both to the relatives and to the court. The second concerns a deceased child managed within the protocol for sudden infant death syndrome. The autopsy was not authorized by the parents and no answer on the causes of death could be determined. These 2 observations underline the importance and utility of this medical act.


Atomic Layer MoS2xTe2(1-x) Ternary Alloys: Two-Dimensional van der Waals Growth, Band gap Engineering, and Electrical Transport.
Ternary alloys in two-dimensional (2D) transition-metal dichalcogenides allow band gap tuning and phase engineering and change the electrical transport type. A process of 2D van der Waals epitaxial growth of molybdenum sulfide telluride alloys (MoS2xTe2(1-x), 0 ≤ x ≤ 1) is presented for synthesizing few-atomic-layer films on SiO2 substrates using metal-organic chemical vapor deposition. Raman spectra, X-ray photoelectron spectra, photoluminescence (PL), and electrical transport properties of few-atomic-layer MoS2xTe2(1-x) (0 ≤ x ≤ 1) films are systematically investigated. The strong PL peaks at 80 K from MoS2xTe2(1-x) (0.45 ≤ x ≤ 0.93) reveal a composition-controllable optical band gap (Eg = 1.55-1.91 eV at 80 K). Electrical transport properties of MoS2xTe2(1-x) alloys, where 0 ≤ x ≤ 0.8 and 0.93 ≤ x ≤ 1, exhibit p-type and n-type semiconducting behaviors, respectively. Remarkably, an increase in the Te composition of a few-atomic-layer MoS2xTe2(1-x) (0 ≤ x ≤ 1) film left-shifts the threshold voltage of a MoS2xTe2(1-x) (0 ≤ x ≤ 1) field-effect transistor. The narrower band gap energies of MoS2xTe2(1-x) films with higher Te content cause a decrease in the on/off current ratios.


The effect of nacom (L-dopa and L-carbidopa) on growth hormone secretion in 75 patients with short stature.
The stimulatory effect of Nacom (250 mg L-Dopa and 25 mg L-Carbidopa) on the HGH secretion was evaluated in 75 short stature patients. The number of blood samples was restricted to only three (0, 45 and 90 min). 63 patients reached adequate HGH concentrations after the ingestion of 1 tablet Nacom (84%). Somatotropin levels increased from 2.08 (Sx 0.28) to a maximal HGH value of 14.22 (Sx 0.87) ng/ml. When the stimulatory effect of Nacom was compared with the standard method of arginine infusion in children with normal stature the arginine test was not superior to the Nacom-test. The Nacom-test appears to be a simple and reliable screening method for HGH deficiency, particularly in outpatients.


Suppression of experimental allergic encephalomyelitis by mitoxantrone.
Treatment of rats with a developing or an established lesion of experimental allergic encephalomyelitis (EAE) with mitoxantrone (Novantrone) suppressed the hind limb paralysis associated with the disease. Histopathological examination of the spinal cords of these rats showed that mitoxantrone-treated rats had reduced vascular lesions that are associated with EAE. Spleen cells derived from immunized rats that had been treated in vivo with mitoxantrone did not transfer disease when these cells were administered to naive syngenic recipients. In addition, spleen cells from diseased rats did not transfer EAE lesions when these cells were administered to recipients that had been treated with mitoxantrone. Recipients treated with mitoxantrone were resistant to EAE lesions induced by sensitized cells in a rapid passive transfer system. Finally, when spleen cells from rats with EAE were incubated, in vitro, with mitoxantrone, these cells did not transfer disease to recipients. Thus the present studies indicate that treatment with mitoxantrone can suppress the lesions associated with both the active and passive forms of EAE.


Automating the Classification of Complexity of Medical Decision-Making in Patient-Provider Messaging in a Patient Portal.
Patient portals are consumer health applications that allow patients to view their health information. Portals facilitate the interactions between patients and their caregivers by offering secure messaging. Patients communicate different needs through portal messages. Medical needs contain requests for delivery of care (e.g. reporting new symptoms). Automating the classification of medical decision complexity in portal messages has not been investigated. We trained two multiclass classifiers, multinomial Naïve Bayes and random forest on 500 message threads, to quantify and label the complexity of decision-making into four classes: no decision, straightforward, low, and moderate. We compared the performance of the models to using only the number of medical terms without training a machine learning model. Our analysis demonstrated that machine learning models have better performance than the model that did not use machine learning. Moreover, machine learning models could quantify the complexity of decision-making that the messages contained with 0.59, 0.45, and 0.58 for macro, micro, and weighted precision and 0.63,0.41, and 0.63 for macro, micro, and weighted recall. This study is one of the first to attempt to classify patient portal messages by whether they involve medical decision-making and the complexity of that decision-making. Machine learning classifiers trained on message content resulted in better message thread classification than classifiers that employed medical terms in the messages alone.


Toxicity of tributyltin in the marine mollusc Mytilus edulis.
Our previous studies have demonstrated that tributyltin (TBT) is genotoxic to the early life stages of marine mussels and worms. Here, the toxicity of TBT to adult organisms was determined using a suite of biomarkers designed to detect cytotoxic, immunotoxic and genotoxic effects. Exposure of adult mussels, Mytilus edulis, to environmentally realistic concentrations of TBTO for 7 days resulted in a statistically significant decrease in cell viability at concentrations of 0.5 microg/l and above. TBT had no effect on phagocytic activity or antioxidant capacity (FRAP assay). There was a statistically significant increase in DNA damage detected using the comet and micronucleus assays between the controls and 0.5, 1 and 5 microg/l of TBTO (P > 0.0005). Furthermore there was a strong correlation between DNA strand breaks (comet assay) and formation of micronuclei (P = 0.0005; R2 = 61.5%). Possible mechanisms by which TBT could damage DNA either directly or indirectly are discussed including the possibility that TBT is genotoxic due to its ability to disrupt calcium homeostasis.


Rare cancer cell analyzer for whole blood applications: microcytometer cell counting and sorting subcircuits.
We demonstrate sorting of rare cancer cells from blood using a thin ribbon monolayer of cells within a credit-card sized, microfluidic laboratory-on-a-card ("lab card") structure. This enables higher cell throughput per minute thereby speeding up cell interrogation. In this approach, multiple cells are viewed and sorted, not individually, but as a whole cell row or section of the ribbon at a time. Gated selection of only the cell rows containing a tagged rare cell provides enrichment of the rare cell relative to background blood cells. We also designed the cell injector for laminar flow antibody labeling within 20s. The approach combines rapid laminar flow cell labeling with monolayer cell sorting thereby enabling rare cell target detection at sensitivity levels 1000 to 10,000 times that of existing flow cytometers. Using this method, total cell labeling and data acquisition time on card may be reduced to a few minutes compared to 30-60 min for standard flow methods.


Gut Microbiota Alternation in Disease Progression of Neurosyphilis.
The gut microbiota plays an important role in the development of neurological disorders such as Parkinson's disease and Alzheimer's disease. However, studies on the gut microbiota of patients with neurosyphilis (NS) were rarely reported. In this study, we collected fecal samples from 62 syphilis patients, including 39 with NS and 23 with non-NS. Among the NS patients, 18 were general paresis (GP). The white blood cell counts, protein concentrations, and Venereal Disease Research Laboratory test positive rates of cerebrospinal fluid from patients in NS or GP group were significantly higher than those from patients in non-NS group. 16S ribosomal RNA sequencing results revealed that the alpha and beta diversities of the gut microbiota were similar between NS and non-NS patients or GP and non-NS patients. Linear discriminant analysis with effect size (LEfSe) analysis showed that some taxa, such as Coprobacter, were increased in both NS group and GP group, compared with non-NS group. Besides, the clade of Akkermansia was also overrepresented in GP Patients. Meanwhile, some taxa such as Clostridia_UCG-014 and SC-I-84 were underrepresented in NS patients. The abundances of class Bacilli and genus Alloprevotella were decreased in GP patients. Among them, the abundances of some taxa such as Coprobacter and Akkermansia have been reported to be associated with other neuropsychiatric disorders. Our findings suggest that the alternation of the gut microbiota in NS patients may contribute to the course of NS, which will deepen our understanding of NS.


Macrophage migration inhibitory factor interacts with thioredoxin-interacting protein and induces NF-κB activity.
The nuclear factor kappa B (NF-κB) pathway is pivotal in controlling survival and apoptosis of cancer cells. Macrophage migration inhibitory factor (MIF), a cytokine that regulates the immune response and tumorigenesis under inflammatory conditions, is upregulated in various tumors. However, the intracellular functions of MIF are unclear. In this study, we found that MIF directly interacted with thioredoxin-interacting protein (TXNIP), a tumor suppressor and known inhibitor of NF-κB activity, and MIF significantly induced NF-κB activation. MIF competed with TXNIP for NF-κB activation, and the intracellular MIF induced NF-κB target genes, including c-IAP2, Bcl-xL, ICAM-1, MMP2 and uPA, by inhibiting the interactions between TXNIP and HDACs or p65. Furthermore, we identified the interaction motifs between MIF and TXNIP via site-directed mutagenesis of their cysteine (Cys) residues. Cys57 and Cys81 of MIF and Cys36 and Cys120 of TXNIP were responsible for the interaction. MIF reversed the TXNIP-induced suppression of cell proliferation and migration. Overall, we suggest that MIF induces NF-κB activity by counter acting the inhibitory effect of TXNIP on the NF-κB pathway via direct interaction with TXNIP. These findings reveal a novel intracellular function of MIF in the progression of cancer.


Experimentally induced Cheyne-Stokes breathing.
We have studied the propensity for periodic breathing to occur in cats anaesthetized with pentobarbitone breathing either spontaneously or with the aid of a 'servo-respirator' governed continuously by the efferent phrenic nerve activity. Sustained periodic breathing could be induced increasing 'controller gain', either by increasing the gain of the respirator, or by lung deflation, which reflexly increased controller responses to both hypoxia and hypercapnia. Periodic breathing was potentiated both by hypoxia and by diminishing the central (CO2, H+)-drive by focal cooling at the ventral surface of the medulla, two procedures which increase the relative influence of hypoxic drive. Less hypoxia was needed to produce periodic breathing at high rather than low controller gains. Reducing controller gain to zero by constant artificial respiration always abolished periodic breathing. Periodic breathing was also eradicated when the relative importance of CO2 drive was enhanced by breathing the cats with CO2-enriched gas mixtures or with 100% O2. The results are consistent with theoretical predictions for the occurrence of oscillations in the mechanisms for the chemical control of breathing and indicate that increasing controller gas can produce periodic breathing. The results further emphasize the importance of the (CO2, H+)-drive in preserving ventilatory stability.


[Eco-physiological investigations on wild and cultivated plants in the Negev Desert : II. The influence of climatic factors on carbon dioxide exchange and transpiration at the end of the dry period].
The influence of climatic factors on net photosynthesis, dark respiration and transpiration was investigated in the Negev Desert at the end of the dry summer period when plant water stress was at a maximum. Species studied included: dominant species of the natural vegetation (Artemisia herba-alba, Hammada scoparia, Noaea mucronata, Reaumuria negevensis, Salsola inermis, Zygophyllum dumosum), cultivated plants receiving rainfall and run-off water during the winter season in the run-off farm Avdat (Prunus armeniaca, Vitis vinifera), and irrigated cultivated plants receiving additional water during the summer season (Citrullus colocynthis, Datura metel). 1. Light saturation of net photosynthesis was reached at 60-90 klx conforming to the high solar radiation intensities of the desert. 2. Maximum rates of CO2 uptake per unit of dry weight for the irrigated mesomorphic plants was ten times that of the wild plants. However, in comparison to the other species, maximal rates of CO2 uptake for wild plants were higher when calculated on a leaf area basis than when represented on a dry weight basis. Maximum rates of net photosynthesis per unit chlorophyll content for some of the wild plants (Salsola and Noaea) were comparable to those of the cultivated Vitis and irrigated Citrullus and Datura, Hammada exhibited even higher rates than Prunus. This demonstrates the great photosynthetic capacity of the wild plants even at the end of the dry season. 3. The upper temperature compensation point for net photosynthesis of the wild plants was unusually high as an adaptation to the temperatures of the habitat. Compensation points higher than 49°C exceed the maxima known so far for other flowering species. Maximum rates of net photosynthesis of Hammada were measured when the temperature of the photosynthetic organs was 37°C; at 49°C photosynthesis was only reduced by 50%. 4. Leaf temperature affects plant gas exchange by influencing stomatal aperture. Diffusion resistance of leaves to water vapour was reduced at low temperatures and increased at high temperatures. Reduction of net photosynthesis and transpiration of desert plants at midday may, therefore, be the result of temperature-induced stomatal closure. The possible influence of peristomatal transpiration on stomatal aperture is also discussed. Peristomatal transpiration is directly related to the vapour pressure gradient between the leaf mesophyll and the ambient air which increases with increasing temperatures. 5. Diffusion resistance to water vapour was reduced at high temperatures approaching the limits of heat resistance, due to increased stomatal aperture. This resulted in greater transpirational cooling. 6. Under conditions of increased leaf water stress, diffusion resistance increased, either by sudden stomatal closure at specific threshold values of water stress or through a continuous increase in resistance. This increased resistance is coupled with decreases in transpiration and photosynthesis. 7. In several plant species increased diffusion resistance during the course of the day caused decreased transpiration without a corresponding decrease in photosynthesis. Under these conditions, the ratio of CO2 uptake to transpiration became more favourable as the day progressed. The possibility that this favourable gas exchange response is the result of an increased mesophyll resistance to water vapour loss is discussed.


Choledochal cyst presenting as acute pancreatitis: evaluation with endoscopic retrograde cholangiopancreatography.
A unusual case of choledochal cyst in an adult presenting as acute pancreatitis is described. Subsequent evaluation by ERCP revealed two atypical features, involvement of the cystic duct (proximal dilatation) and a long (six times normal) intrapancreatic common channel, which may be etiologically related to the pancreatitis.


The Information-Seeking Behavior and Unmet Knowledge Needs of Older Medicinal Cannabis Consumers in Canada: A Qualitative Descriptive Study.
Older Canadians (age 60+) are increasingly using cannabis to treat their health problems, but little is known regarding how they learn about medicinal cannabis. This study explored the perspectives of older cannabis consumers, prospective consumers, healthcare professionals, and cannabis retailers on older adults' information-seeking behavior and unmet knowledge needs. A qualitative descriptive design was used. Semi-structured telephone interviews were conducted with a purposeful sample of 36 older cannabis consumers and prospective consumers, as well as 4 healthcare professionals and 5 cannabis retailers from across Canada, for a total sample of 45 participants. Data were thematically analyzed. Three main themes characterizing older cannabis consumers' information-seeking were identified: (1) knowledge sources, (2) types of information sought, and (3) unmet knowledge needs. Participants accessed a variety of knowledge sources to inform themselves about medicinal cannabis. Cannabis retailers were identified as providing medical information to many older adults, despite regulations to the contrary. Cannabis-specialized healthcare professionals were also viewed as key knowledge sources, while primary care providers were perceived as both knowledge sources and gatekeepers limiting access to information. The types of information participants sought included the effects and potential benefits of medicinal cannabis, the side effects and risks involved, and guidance regarding suitable cannabis products. Participants' most salient unmet knowledge needs focused on dosing and use of cannabis to treat specific health conditions. Findings suggest that barriers to learning about medical cannabis among older consumers identified in prior research remain pervasive and cut across jurisdictions. To address these barriers, there is a need for better knowledge products tailored to older cannabis consumers and their information needs, and further education for primary healthcare providers on medicinal cannabis and its therapeutic applications with older patients.


Improved procedure for the bimolecular oxidative amidation of phenols.
Trifluoroacetic acid (TFA) is an effective promoter of the bimolecular Ritter-like oxidative amidation of 4-substituted phenols induced by PhI(OAc) 2 in MeCN. This suppresses the need for fluoroalcohol cosolvents, increases the yields, and facilitates isolation/purification procedures.


Optimizing the DNA yield for molecular analysis from cytologic preparations.
Cytology smears and cytospin preparations are increasingly being used for molecular testing. With these limited samples, optimizing tissue extraction to maximize the DNA yield is, therefore, critical. This study examined 2 common methods of tissue extraction and compared DNA yields from different types of glass slides. The H226 lung cancer cell line and 5 clinical samples of cellular effusions were used to prepare Diff-Quik-stained cytospins on 4 types of glass slides: fully frosted (FF), nonfrosted (NF), positively charged (PC), and silane-coated (SC). Tissue extraction was performed by either scalpel-blade scraping or cell lifting with the Pinpoint Slide DNA Isolation System (Zymo Research). DNA was extracted with the QIAamp DNA Mini Kit (Qiagen) and was quantified with the Quant-iT PicoGreen Kit (Life Technologies). The DNA yield in cell-line cytospins was significantly lower from FF slides versus NF, PC, and SC slides with both scraping and cell-lifting methods. In addition, scraping yielded significantly more DNA than cell lifting (P = .005). DNA yields from 5 clinical effusion cases with FF and NF slides showed results similar to the results for cell-line samples, with scraping consistently yielding more DNA than cell lifting and with NF slides outperforming FF slides. Optimizing the DNA yield extracted from cytology specimens maximizes the chances of successful molecular testing and is critical in cases of low or marginal cellularity. This study demonstrates the following: 1) scraping yields more DNA than cell lifting, and 2) NF slides yield more DNA than FF slides.


Is sexual life influenced by transdermal estrogen therapy? A double blind placebo controlled study in postmenopausal women.
Two hundred and forty-two postmenopausal women between 45 and 65 years of age requiring hormone replacement therapy for climacteric symptoms were blindly and randomly allocated to treatment either with transdermal estradiol therapy (Estraderm 50 micrograms/24h) (E) or placebo (P). The patches were changed twice a week and treatment continued for 12 weeks. No progestogen supplement therapy was given during the study. No previous hormone replacement therapy had been given for the last six months and the women had had their last menstruation more than six months ago. As a part of a larger study assessing women's quality of life, a Swedish version of 'McCoy's Sex Scale Questionnaire' was administered at the start of treatment and after 12 weeks. This questionnaire contains nine items regarding different aspects of sexual life. The difference between the scorings at the start of treatment and after 12 weeks were calculated for each item and the values of the E and the P groups were compared. Items regarding 'satisfaction with frequency of sexual activity, sexual fantasies, degree of enjoyment, vaginal lubrication and pain during intercourse' were positively influenced in the E group compared to the P group. Items not affected were 'frequency of orgasm and sexual arousal'. A correlation between improved sexual life and quality of life was also found when the results from the McCoy scale were compared with a battery of quality of life questionnaires.


Endothelial calpain systems orchestrate myofibroblast differentiation during wound healing.
The transformation of fibroblasts to myofibroblasts plays a major role in fibrogenic responses during dermal wound healing. We show a contribution of calpain systems (intracellular regulatory protease systems) in vascular endothelial cells (ECs) to myofibroblast differentiation in wound sites. Dermal wound healing experiments in mice found that calpastatin (an endogenous inhibitor of calpains) is enriched in preexisting vessels but not in newly formed capillaries. Transgenic overexpression of calpastatin in ECs delayed wound healing in mice as well as reducing the keratinocyte layer, extracellular matrix deposition, and myofibroblast accumulation in wound sites. EC and leukocyte markers, however, remain unchanged. Calpastatin overexpression reduced the expression of genes encoding platelet-derived growth factor-B and PDGF receptor-β (PDGFR-β). Topical application of platelet-derived growth factor-BB-containing ointment to wounds accelerated healing in control mice, but calpastatin overexpression prevented this acceleration. In cultured human dermal fibroblasts, α-smooth muscle actin and PDGFR-β were up-regulated by coculturing with ECs, but this action was inhibited by suppression of EC calpain activity. EC-driven transformation of mouse dermal fibroblasts was also suppressed by calpastatin overexpression in ECs. These results suggest that endothelial calpain systems influence PDGFR-β signaling in fibroblasts, EC-driven myofibroblast differentiation, and subsequent fibrogenic responses in wounds.-Miyazaki, T., Haraguchi, S., Kim-Kaneyama, J.-R., Miyazaki, A. Endothelial calpain systems orchestrate myofibroblast differentiation during wound healing.


When is 'Urgent' Really Urgent and Does it Matter? Misclassification of Procedural Status and Implications for Risk Assessment in Cardiac Surgery.
Many patients classified as "urgent" in Australia New Zealand Society of Cardiac and Thoracic Surgeons (ANZSCTS) registry contradict the prescribed definition (surgery within 72hours of angiogram or unplanned admission). The aim was to examine the impacts of this misclassification on the prediction of 30-day mortality following cardiac surgery. The 'reported clinical status' was compared with a 'corrected clinical status' following reclassification based on the standard definition calculated from raw data. Observed-to-predicted risk ratios (OPRs) of 30-day mortality were calculated for the model using reported status and corrected status and compared. A Bland-Altman plot was generated to examine the level of agreement between the two OPRs. Of 18496 cases reported as urgent, 49.9% were operated after 72hours, leading to misclassification of 14.6% in the registry. Misclassified patients had significantly higher mortality (3.5%) than true urgent patients (2.9%). Underweight (OR:1.6,CI:1.2-2.1), dialysis (OR:1.4,CI:1.1-1.7), endocarditis (OR:2.1,CI:1.7-2.5), shock (OR:1.6,CI:1.3-2.0) and poor ejection fraction (OR:1.2,CI:1.1-1.4) were significant predictors of misclassification. Bland- Altman plot demonstrates significant disagreement between two risk estimates (P<0.001). Misclassification results in overestimation of risk by 9.1%. Observed-to-predicted risk increased with corrected definition (0.8975 vs 0.9875), suggesting poorer calibration with reported status. In the ANZSCTS database, misclassification prevalence is 14.6%. Misclassification compromises the discrimination capacity and calibration of the model and results in overestimation of mortality risk.


Transcriptional regulation by methyltransferases and their role in the heart: highlighting novel emerging functionality.
Methyltransferases are a superfamily of enzymes that transfer methyl groups to proteins, nucleic acids, and small molecules. Traditionally, these enzymes have been shown to carry out a specific modification (mono-, di-, or trimethylation) on a single, or limited number of, amino acid(s). The largest subgroup of this family, protein methyltransferases, target arginine and lysine side chains of histone molecules to regulate gene expression. Although there is a large number of functional studies that have been performed on individual methyltransferases describing their methylation targets and effects on biological processes, no analyses exist describing the spatial distribution across tissues or their differential expression in the diseased heart. For this review, we performed tissue profiling in protein databases of 199 confirmed or putative methyltransferases to demonstrate the unique tissue-specific expression of these individual proteins. In addition, we examined transcript data sets from human heart failure patients and murine models of heart disease to identify 40 methyltransferases in humans and 15 in mice, which are differentially regulated in the heart, although many have never been functionally interrogated. Lastly, we focused our analysis on the largest subgroup, that of protein methyltransferases, and present a newly emerging phenomenon in which 16 of these enzymes have been shown to play dual roles in regulating transcription by maintaining the ability to both activate and repress transcription through methyltransferase-dependent or -independent mechanisms. Overall, this review highlights a novel paradigm shift in our understanding of the function of histone methyltransferases and correlates their expression in heart disease.


Mirror efficiency in the assessment of visual pursuit in patients in minimally conscious state.
Visual pursuit should be tested with a mirror in patients with disorders of consciousness. This stimulus was indeed more efficient than a person or an object, and the auto-referential aspect was supposed to be the key feature. The present study tested the hypothesis that the mirror was more efficient because of its self-aspect. The mirror was compared (1) to the patient's picture and to the picture of a famous face, in 22 patients in minimally conscious state and (2) to the patient's picture and a fake mirror, which had dynamical and bright aspects of the mirror, without reflecting the face, in 26 other patients in minimally conscious state. The mirror was more efficient than the patient's picture, which was not statistically different from the famous face. The second part of the study confirmed the statistical difference between the mirror and the picture. However, the fake mirror was neither statistically different from the mirror nor from the picture. Although our results suggest that the hypothesis proposed by previous studies was partly wrong, they confirm that the mirror is the best stimulus to use when assessing visual pursuit.


Chromosome localization-dependent compositional bias of point mutations in Alu repetitive sequences.
The Alu repetitive sequence family originated from a common ancestor. Its members, apparently free from functional constraints, are interspersed throughout primate genomes. We have found that base substitutions occurring during the evolution of primates caused a decrease in the average G + C content of those members of the family that are located in an A + T-rich region of the genome. The family members that are located in a G + C-rich genomic region have not changed their, already high, G + C content. This suggests that the regional differences in G + C content, which are responsible for chromosomal banding, are caused by an accumulation of mutations that, although selectively neutral in the majority, show different compositional bias in different regions of the vertebrate chromosome.


A Phase 2, Randomized, Dose-Finding Study of the Novel Once-Weekly Human GLP-1 Analog, Semaglutide, Compared With Placebo and Open-Label Liraglutide in Patients With Type 2 Diabetes.
To investigate the dose-response relationship of semaglutide versus placebo and open-label liraglutide in terms of glycemic control in patients with type 2 diabetes. This was a 12-week, randomized, double-blind phase 2 trial. Patients (n = 415) were randomized to receive a subcutaneous injection of semaglutide once weekly without dose escalation (0.1-0.8 mg) or with dose escalation (E) (0.4 mg steps to 0.8 or 1.6 mg E over 1-2 weeks), open-label liraglutide once daily (1.2 or 1.8 mg), or placebo. The primary end point was change in HbA1c level from baseline. Secondary end points included change in body weight, safety, and tolerability. Semaglutide dose-dependently reduced the level of HbA1c from baseline (8.1 ± 0.8%) to week 12 by up to -1.7%, and body weight by up to -4.8 kg (1.6 mg E, P < 0.001 vs. placebo). Up to 81% of patients achieved an HbA1c level of <7%. HbA1c level and weight reductions with semaglutide 1.6 mg E were greater than those with liraglutide 1.2 and 1.8 mg (based on unadjusted CIs), but adverse events (AEs) and withdrawals occurred more frequently. The incidence of nausea, vomiting, and withdrawal due to gastrointestinal AEs increased with the semaglutide dose; most events were mild to moderate, transient, and ameliorated by dose escalation. There were no major episodes of hypoglycemia and few cases of injection site reactions. After 12 weeks, semaglutide dose-dependently reduced HbA1c level and weight in patients with type 2 diabetes. No unexpected safety or tolerability concerns were identified; gastrointestinal AEs typical of glucagon-like peptide 1 receptor agonists were mitigated by dose escalation. On this basis, weekly semaglutide doses of 0.5 and 1.0 mg with a 4-week dose escalation were selected for phase 3.


Hepatitis B surface antigen specific cytotoxic T lymphocyte activity in hepatitis B virus infection.
Cytotoxic T lymphocyte (CTL) activity against HBs antigen (HBsAg)-coated autologous mononuclear cells as target cells was examined in hepatitis B virus infection. Target cells were prepared by coincubation of mononuclear cells with purified HBsAg in 0.5 mM CrCl3. The distribution and uniformity amounts of HBsAg on target cells was shown by immune fluorescence and by analyzing the fluorescence intensity with a fluorescent activated cell sorter. CTL activity was detected in 7 of 9 patients with acute hepatitis type B, in 4 of 11 chronic active hepatitis type B, in none of 8 healthy HBsAg carriers, and in none of 22 healthy volunteers. The antigen specificity of the cytotoxicity was confirmed by a blocking experiment with purified HBsAg and by cold target inhibition with HBsAg or bovine serum albumin (irrelevant antigen) coupled cold target cells. CTL lysed HBsAg coupled allogeneic target cells that shared HLA-A or B locus antigens. This finding suggests that HLA restriction may be involved in the killing mechanism. This HBsAg specific CTL clone may participate in the immunopathogenesis of hepatitis B virus infection.


Genomics of hypertension: the road to precision medicine.
The known genetic architecture of blood pressure now comprises >30 genes, with rare variants resulting in monogenic forms of hypertension or hypotension and >1,477 common single-nucleotide polymorphisms (SNPs) being associated with the blood pressure phenotype. Monogenic blood pressure syndromes predominantly involve the renin-angiotensin-aldosterone system and the adrenal glucocorticoid pathway, with a smaller fraction caused by neuroendocrine tumours of the sympathetic and parasympathetic nervous systems. The SNPs identified in genome-wide association studies (GWAS) as being associated with the blood pressure phenotype explain only approximately 27% of the 30-50% estimated heritability of blood pressure, and the effect of each SNP on the blood pressure phenotype is small. A paucity of SNPs from GWAS are mapped to known genes causing monogenic blood pressure syndromes. For example, a GWAS signal mapped to the gene encoding uromodulin has been shown to affect blood pressure by influencing sodium homeostasis, and the effects of another GWAS signal were mediated by endothelin. However, the majority of blood pressure-associated SNPs show pleiotropic associations. Unravelling these associations can potentially help us to understand the underlying biological pathways. In this Review, we appraise the current knowledge of blood pressure genomics, explore the causal pathways for hypertension identified in Mendelian randomization studies and highlight the opportunities for drug repurposing and pharmacogenomics for the treatment of hypertension.


Safety and Clinical Response Following a Repeat Intraarticular Injection of Tin-117m (117mSn) Colloid in Dogs with Elbow Osteoarthritis.
To determine if a repeat intraarticular (IA) injection of a tin-117m colloid radiosynoviorthesis (RSO) agent can be safely given in the same joint 12 months after an initial injection for treatment of canine elbow osteoarthritis (OA), and to evaluate the pain reduction effect of the repeat injection. Nine client owned dogs with grade 1 or 2 elbow OA were given an IA injection of tin-117m colloid in both elbows, one of which had been treated ≤12 months earlier with the same RSO device. Treatment safety was evaluated by joint fluid analysis at baseline (BL) and at 180 days after treatment, and by urinalysis, CBC, and serum chemistry analysis of diagnostic samples obtained at BL and 180 days. Radiographs, computed tomography, and MRI scans were obtained at BL and 180 days to determine if disease progression differed in elbows given one versus two injections. Clinical response to treatment was assessed subjectively by dog owner responses to the Canine Brief Pain Inventory (CBPI) survey at BL, 90 and 180 days, and objectively by investigator-conducted force plate (FP) analysis of dogs at BL, 90, and 180 days. All post-treatment urinalysis, CBC and clinical chemistry results were within normal ranges. Joint fluid analysis showed a significant (P=0.0411) reduction in the percentage of monocytes at 180 days, consistent with the tin-117m colloid mode of action of apoptosis of pro-inflammatory macrophages at the injection site. There was no significant difference in OA progression in elbows given one or two injections. The treatment success rate was 55.5% (5/9) on day 90 as determined either by CBPI responses or FP analysis, and 66.6% (6/9) on day 180 as determined by FP analysis. The tin-117m colloid can be safely given as a repeat injection 12 months after an initial injection, and can potentially provide a durable therapeutic response in dogs with elbow OA.


Hereditary acanthocytosis associated with the McLeod phenotype of the Kell blood group system.
Some boys with X-linked chronic granulomatous disease (CGD) have red cells of the rare McLeod phenotype in the Kell blood group system. Only one example of this phenotype has previously been described in a non-CGD subject. We have studied a 10-year-old boy and a maternal brother who do not have CGD and whose red cells are of the McLeod type . The boy presented as a haematological problem with red-cell abnormalities. These were acanthocytosis, anisocytosis and 'tailing' in the osmotic fragility curve, changes now known to occur with the McLeod phenotype. Subsequent studies revealed his rare blood group. A family study has established that an uncle also has acanthocytic red cells and the McLeod phenotype. In addition the boy's sister, mother and maternal grandmother all show red-cell mosaicism with double populations of McLeod acanthocytes and normal red cells of common Kell type. The gene that determines inheritance of the McLeod phenotype is X-linked and the mosaicism present in female carriers is believed to result from X chromosome inactivation by the Lyon effect. The study provides further evidence that the McLeod phenotype arises by inheritance of a variant X-linked modifying gene and not through inheritance of a variant gene at the Kell autosomal locus. It also represents the first occasion that a person of rare blood group has been recognized because of an associated anomaly in red cell morphology.


Degradation of lyophilized lipid/DNA complexes during storage: the role of lipid and reactive oxygen species.
The presence of trace amounts of metal ions in nonviral vector formulations can significantly affect the stability of lipid/DNA complexes (lipoplexes) during acute freeze-drying. The goal of the present study was to evaluate the generation of reactive oxygen species (ROS) in dried formulations of lipoplexes and in their individual components (lipid or naked DNA). The experiments were conducted in the presence or absence of a transition metal (Fe2+). Lipoplexes and their individual components were formulated in trehalose and subjected to lyophilization and stored for a period of up to 2 months at +60 degrees C. Physico-chemical characteristics and biological activity were evaluated at different time intervals. Generation of ROS during storage was determined by adding a fluorescence probe to the formulations prior to freeze-drying. We also monitored the formation of thiobarbituric reactive substances (TBARS). Our results show that ROS and TBARS form during storage in the dried state. Our findings also suggest that degradation is more rapid in the presence of lipid, even in the absence of metal. We also showed that dried naked DNA formulations are more stable without the lipid component. Effective strategies are then needed to minimize the formation and accumulation of oxidative damage of lipoplexes during storage.


Solid-phase synthesis of potential protein tyrosine phosphatase inhibitors via the Ugi four-component condensation.
A library of 108 alpha,alpha-difluoromethylenephosphonic acids was prepared by Ugi four-component condensation using Rink-NH2 resin, 4-[(diethoxyphosphinyl) difluoromethyl]benzoic acid, and a set of 18 aldehydes and 6 isonitriles. Following resin cleavage, the diethylphosphonate esters were hydrolyzed with trimethylsilyl bromide to yield the free acids which were assayed for inhibition of PTP alpha, PTP beta and PTP epsilon.


A deep learning-based cancer survival time classifier for small datasets.
Cancer survival time prediction using Deep Learning (DL) has been an emerging area of research. However, non-availability of large-sized annotated medical imaging databases affects the training performance of DL models leading to their arguable usage in many clinical applications. In this research work, a neural network model is customized for small sample space to avoid data over-fitting for DL training. A set of prognostic radiomic features is selected through an iterative process using average of multiple dropouts which results in back-propagated gradients with low variance, thus increasing the network learning capability, reliable feature selection and better training over a small database. The proposed classifier is further compared with erasing feature selection method proposed in the literature for improved network training and with other well-known classifiers on small sample size. Achieved results which were statistically validated show efficient and improved classification of cancer survival time into three intervals of 6 months, between 6 months up to 2 years, and above 2 years; and has the potential to aid health care professionals in lung tumor evaluation for timely treatment and patient care.


Impact of different activation wavefronts on ischemic myocardial scar electrophysiological properties during high-density ventricular tachycardia mapping and ablation.
Scar-related ventricular tachycardia (VT) usually results from an underlying reentrant circuit facilitated by anatomical and functional barriers. The later are sensitive to the direction of ventricular activation wavefronts. We aim to evaluate the impact of different ventricular activation wavefronts on the functional electrophysiological properties of myocardial tissue. Patients with ischemic heart disease referred for VT ablation underwent high-density mapping using Carto®3 (Biosense Webster). Maps were generated during sinus rhythm, right and left ventricular pacing, and analyzed using a new late potential map software, which allows to assess local conduction velocities and facilitates the delineation of intra-scar conduction corridors (ISCC); and for all stable VTs. In 16 patients, 31 high-resolution substrate maps from different ventricular activation wavefronts and 7 VT activation maps were obtained. Local abnormal ventricular activities (LAVAs) were found in VT isthmus, but also in noncritical areas. The VT isthmus was localized in areas of LAVAs overlapping surface between the different activation wavefronts. The deceleration zone location differed depending on activation wavefronts. Sixty-six percent of ISCCs were similarly identified in all activating wavefronts, but the one acting as VT isthmus was simultaneously identified in all activation wavefronts in all cases. Functional based substrate mapping may improve the specificity to localize the most arrhythmogenic regions within the scar, making the use of different activation wavefronts unnecessary in most cases.


Ultrasonically prepared photocatalyst of W/WO3 nanoplates with WS2 nanosheets as 2D material for improving photoelectrochemical water splitting.
A sonochemical treatment has been an emerged technique as an interesting method for fabricating different photocatalysts with unique photoelectrochemical (PEC) properties. This study investigated the PEC performance of WO3 with WS2 nanosheets as a 2D material before calcination (WO3/WS2-90) and after calcination (WO3/WS2-450) prepared with sonochemical treatment. The WS2 nanosheets were prepared from a liquid exfoliation phase with few-layer nanosheets, approximately 6.5 nm in thickness. The nanosheets were confirmed by UV-Vis spectroscopy and atomic force microscopy. Further, XPS, RAMAN, and SEM-EDAX analyses indicated that, following calcination of the WO3/WS2 electrode, the WS2 nanosheets initially transformed to 2D-WO3. After depositing the WS2 nanosheets on the WO3, the photocurrent density increased substantially. The WO3/WS2-450 films after calcination showed a photocurrent density of 5.6 mA.cm-2 at 1.23 V vs. Ag/AgCl, which was 3.1 and 7.2 times higher, respectively than those of the WO3/WS2-90 before calcination and pure WO3. Mott-Schottky and electrochemical impedance spectroscopy analyses confirmed the fabrication of the WO3/WS2 photoanode after calcination. The deposition of WS2 nanosheets onto pure WO3 increased the donor concentration (24-fold), reduced the space charge layer (4.6-fold), and decreased the flat band potential (1.6-fold), which could all help improve the photoelectrochemical efficiency. Moreover, the incorporation of WO3 with WS2 nanosheets as a 2D material (WO3/WS2-450) enhanced the incident photon current efficiency (IPCE) by 55%. In addition, the applied-bias photon-to-current conversion efficiency of the WO3/WS2-450 films was approximately 2.26% at 0.75 V (vs. Ag/AgCl), which is 5.6 and 9 times higher, respectively than those of WO3/WS2-90 and pure WO3.


Association of In Utero HIV Exposure With Obesity and Reactive Airway Disease in HIV-Negative Adolescents and Young Adults.
HIV-negative individuals with in utero HIV exposure represent an emerging population, exceeding 18 million people worldwide. Long-term clinical outcomes among HIV-exposed uninfected (HEU) individuals into adolescence and young adulthood remain unknown. US academic health system. In this observational cohort study, we leveraged a patient data registry to identify 50 HEU adolescents and young adults. We also identified 141 HIV-unexposed controls that were matched to HEU subjects up to 3:1 on age of last encounter (±2 years), birthdate (±5 years), sex, race/ethnicity, and zip code. All subjects were born since January 1, 1990, with medical records available into adolescence and young adulthood. Primary outcomes were most recent body mass index (BMI) z-score and presence of reactive airway disease (RAD). Records were manually reviewed to extract health information. Fifty HEU adolescents and young adults (18 ± 3 years, 54% men) and 141 matched controls (19 ± 3 years, 54% men) were compared. HEU individuals had a higher BMI z-score (1.12 ± 1.08 vs. 0.73 ± 1.09, P = 0.03) and an increased prevalence of obesity (42% vs. 22%, P = 0.009) compared with controls. HEU subjects also had a higher prevalence of RAD vs. controls (40% vs. 23%, P = 0.03). These differences persisted on adjusting for demographic, socioeconomic, maternal, and birth-related factors. Maternal prenatal CD4 T-cell count was inversely associated with BMI z-score among HEU adolescents (r = -0.47, P = 0.01). HEU adolescents and young adults exhibited a heightened prevalence of obesity and RAD compared with HIV-unexposed controls. Additional studies are needed to optimize care for the expanding population of HEU individuals transitioning to adulthood.


Adverse events associated with bone-conduction and middle-ear implants: a systematic review.
To review types and frequencies of adverse events (AE) associated with bone-conduction hearing implants (BCHIs) and active middle-ear implants (aMEIs) as reported in the literature. Cochrane, PubMed, and EMBASE libraries were searched for primary articles in English or German language that reported on adverse events following BCHI or aMEI implantation, included at least five patients and were published between 1996 and 2016. Study characteristics, demographics, and counts of adverse events were tabulated and analyzed within the R statistical programming environment. Following assessment of the reporting quality of adverse events, we present a brief guideline that potentially improves AE reporting in this field of research. For the full dataset, we summarize study-level adverse event frequencies in terms of ratio of events to ears (REE) by AE groups and by device. For a subset of studies, we also report cumulative incidence (risk) for minor- and major adverse-events by device and by device groups. Data analyzed in this review show that: (1) the reporting quality of adverse events associated with BCHI and aMEIs is often very low; (2) adverse events associated with BCHI and aMEIs are qualitatively different and not equally frequent among devices; (3) state-of-the-art implantable BCHIs and aMEIs are a safe treatment option for hearing loss.


Socioeconomic characteristics of the community in childhood and cognition in old age.
We examined the relation of early life socioeconomic circumstances to cognition in older residents of a biracial urban community. Participants had brief cognitive testing three times at approximately 3-year intervals. At baseline, information about early life household and county socioeconomic level was collected. In mixed-effects models adjusted for age, sex, race, and education, both early life household and county socioeconomic levels were positively associated with baseline level of cognition but unrelated to cognitive decline. The results suggest that socioeconomic conditions in early life are associated with level of cognitive function in old age but not with rate of cognitive decline.


Phasic modulation of transmission from vestibular inputs to reticulospinal neurons during fictive locomotion in lampreys.
The aim of this study was to determine whether the transmission from sensory inputs to reticulospinal neurons is modulated during fictive locomotion in lampreys. Reticulospinal neurons play a key role in the control of locomotion; modulation of sensory transmission to these neurons might be of importance for the adaptation of the control they exert during locomotion. In this series of experiments, intracellular synaptic responses of reticulospinal neurons of the posterior rhombencephalic reticular nucleus elicited by electrical stimulation of vestibular nerves on each side were studied during fictive locomotion induced by 50 microM N-methyl-D-aspartate (NMDA). Interestingly, shortly after NMDA had reached the bath and much before locomotor discharges were apparent in the recorded ventral roots, there was a significant depression of the synaptic transmission from vestibular nerves. The effect was reversed by washing out the NMDA and persisted in the isolated brainstem after spinal transection at the first segmental level. As locomotor discharges appeared in the ventral roots, synaptic responses elicited by vestibular nerve stimulation showed a clear phasic modulation of their amplitude during the locomotor cycle. Responses to stimulation of the ipsilateral vestibular nerve were smaller during the ipsilateral burst discharge than during the contralateral activity, whilst responses to stimulation of the contralateral vestibular nerve were minimal during contralateral activity and maximal during ipsilateral activity. This opposite pattern of modulation observed in the same reticulospinal neuron suggests that the phasic modulation of vestibular transmission is not due to changes in the membrane properties of the reticulospinal cell but is produced at a pre-reticular level.(ABSTRACT TRUNCATED AT 250 WORDS)


Relaxation rates of blood with osmotically modified red cell volume: application of the two-compartment fast exchange model.
Blood has been considered as a simplified tissue model, both physiologically and physically consisting in two compartments, extra-cellular and intra-cellular. In the physiologic condition (300 mOsm), the relaxation rates of red cell suspensions in saline increased linearly with the hematocrit in the range 0-0.80 according to Fullerton's model of fast proton exchanges between the two compartments (Fullerton GD, Potter JL, Dornbluth NC. NMR relaxation of protons in tissues and other macromolecular water solutions. Magn Reson Imaging 1982; 1:209-228). In experiments of osmotic variations, between 200 and 900 mOsm at three constant red cell numbers in the samples, non-linear variations of relaxation rates with red cell volume were observed. In the hyperosmotic domain, the particularly high increase in blood transverse relaxation rate with the decreasing cell volume has been attributed to the progressive water-protein organization in the cellular compartment. A generalised form of the fast exchange model has been applied to extended experimental conditions of red cells, by introducing the red cell volume ratio of modified to iso-osmotic values, and the volume fraction of iso-osmotic red cells.


Immunohistochemical demonstration of altered functional differentiation of pancreatic tissue in sacrococcygeal teratomas.
The finding of teratomas with mature-appearing pancreatic tissue showing abnormal production of immunoreactive amylase appears to contradict earlier suggestions that somatic tissue in teratomas that appears mature also functions normally. It therefore seems judicious to study carefully both morphologic and functional characteristics of tissues in teratomas before utilizing them as experimental models of tissue differentiation, since at least in the case of human amylase, functional differentiation does not always follow morphologic differentiation.


Ruptured intracranial aneurysms in the elderly: epidemiology, diagnosis, and management.
Spontaneous subarachnoid hemorrhage (SAH) is often a devastating condition and a significant cause of worldwide morbidity and mortality. Because the percentage of senior citizens is increasing in many countries and because of the increased incidence of SAH in elderly patients, ruptured intracranial aneurysm is an increasingly frequent pathology in western countries. Twenty years ago, older people were considered to have such a poor prognosis that they were frequently excluded from active treatment on the unique basis of their advanced age. Improving results published in recent studies showed that the classic fatalistic attitude associated with age and intracranial aneurysm (IA) should be reconsidered. Therefore, because of improvements in surgical results and neuro-intensive care, the appearance of interventional neuroradiology, and more aggressive rehabilitation programs, the management of ruptured IA in the elderly is changing. This article aims to review epidemiology, emphasize the specific aspects of the disease in the elderly, and present the current management of SAH in an elderly population.


Effects of transdermal and oral postmenopausal hormone therapy on vascular function: a randomized, placebo-controlled study in healthy postmenopausal women.
To compare the effect of transdermal and oral estrogen therapy, the latter with or without the addition of gestodene, on plasma concentrations of markers of endothelial function and on ultrasonographic parameters of vascular function in healthy postmenopausal women. In a 15-month, randomized, double-blind, placebo-controlled study, 152 healthy hysterectomized postmenopausal women received daily doses of placebo (n = 49), 50 microg of transdermal 17ss-estradiol (tE2, n = 33), 1 mg of oral E2 (oE2, n = 37), or 1 mg of oral estradiol combined with 25 microg of gestodene (oE2+ G, n = 33) for 13 cycles of 28 days, followed by four washout cycles with placebo in each group. At baseline and in cycles 4, 13, and 17, we measured plasma levels of endothelial markers and ultrasonographic markers of vascular function (pulsatility index [PI] and, at baseline and cycle 13, arterial stiffness). Compared with placebo, we found reductions in soluble vascular cell adhesion molecule (oE2, P < 0.01; oE2+ G, P < 0.001), sE-selectin (oE2 + G, P < 0.05), von Willebrand factor (tE2, P < 0.05), and divergent effects in PI and stiffness parameters in the carotid artery. We found no effect on PI in the retinal and femoral arteries, or on stiffness parameters in the femoral and brachial artery. Oral hormone therapy reduced plasma levels of adhesion molecules, whereas transdermal estrogen therapy reduced von Willebrand factor. Effects on ultrasonographic parameters of vascular function in the carotid artery were inconclusive.


Comparative transcriptomic analyses to scrutinize the assumption that genotoxic PAHs exert effects via a common mode of action.
In this study, the accuracy of the assumption that genotoxic, carcinogenic polycyclic aromatic hydrocarbons (PAHs) act via similar mechanisms of action as benzo(a)pyrene (BaP), the reference PAH used in the human health risk assessment of PAH-containing complex mixtures, was investigated. Adult male Muta™Mouse were gavaged for 28 days with seven individual, genotoxic PAHs. Global gene expression profiles in forestomach, liver, and lung (target tissues of exposure) were determined at 3 days post-exposure. The results are compared with our previously published results from mice exposed to BaP via the same exposure regimen. Although all PAHs showed enhanced ethoxyresorufin-O-deethylase activity, DNA adduct formation, and lacZ mutant frequency in the lungs, the unsupervised cluster analysis of differentially expressed genes revealed that the transcriptional changes are both PAH- and tissue-specific, with lung showing the most response. Further bioinformatics-/pathway-based analysis revealed that all PAHs induce expression of genes associated with carcinogenic processes, including DNA damage response, immune/inflammatory response, or cell signaling processes; however, the type of pathways and the magnitude of change varied for each PAH and were not the same as those observed for BaP. Benchmark dose modeling showed transcriptomic data closely reflected the known tumor incidence for the individual PAHs in each tissue. Collectively, the results suggest that the underlying mechanisms of PAH-induced toxicity leading to tumorigenesis are tissue-specific and not the same for all PAHs; based on the tissue type considered, use of BaP as a reference chemical may overestimate or underestimate the carcinogenic potential of PAHs.


Effect of antibiotic treatment of young calves on glucose absorption and some plasma components.
Oral treatment of 10-15 day-old calves with either chloramphenicol (55 mg/kg body wt) or tetracycline (11 mg/kg body wt) did not induce diarrhoea. Treatment caused significant elevation of plasma Na+, K+ and total protein. Calves treated with chloramphenicol showed retarded glucose absorption from the gut.