Photomemristive sensing via charge storage in 2D carbon nitrides.
Photomemristive sensors have the potential to innovate current photo-electrochemical sensors by incorporating new sensing capabilities including non-invasive, wireless and time-delayed (memory) readout. Here we report the charge storing 2D carbon nitride potassium poly(heptazine imide), K-PHI, as a direct photomemristive sensing platform by capitalizing on K-PHI's visible light bandgap, large oxidation potential, and intrinsic optoionic charge storage properties. Utilizing the light-induced charge storage function of K-PHI nanosheets, we demonstrate memory sensing via charge accumulation and present potentiometric, impedimetric and coulometric readouts to write/erase this information from the material, with no additional reagents required. Additionally, wireless colorimetric and fluorometric detection of the charging state of K-PHI nanoparticles is demonstrated, enabling the material's use as particle-based autonomous sensing probe in situ. The various readout options of K-PHI's response enable us to adapt the sensitivities and dynamic ranges without modifying the sensing platform, which is demonstrated using glucose as a model analyte over a wide range of concentrations (50 μM to 50 mM). Since K-PHI is earth abundant, biocompatible, chemically robust and responsive to visible light, we anticipate that the photomemristive sensing platform presented herein opens up memristive and neuromorphic functions.


Factors attributing to the failure of endometrial sampling in women with postmenopausal bleeding.
To determine which doctor- and patient-related factors affect failure of outpatient endometrial sampling in women with postmenopausal bleeding, and to develop a multivariable prediction model to select women with a high probability of failed sampling. Prospective multicenter cohort study. Three teaching hospitals in the Netherlands. Women presenting with postmenopausal bleeding with an indication for endometrial sampling. Multivariable logistic regression was performed to evaluate the impact of doctor's training level and patient's characteristics on failure of sampling. Failure of endometrial sampling, classified as technical failure or insufficient tissue for diagnosis. In 74 (20.8%) of the 356 included women, sampling technically failed, and in 84 (29.8%) the amount of tissue was insufficient for diagnosis. Nulliparity [odds ratio (OR) 3.8, 95% confidence interval (CI) 1.8-7.9] and advanced age (OR 1.03 per year, 95% CI 1.00-1.06) were associated with technical failure. Advanced age was associated with insufficient sampling (OR 1.04 per year, 95% CI 1.01-1.07), and endometrial thickness >12 mm decreased the chance of insufficient sampling (OR 0.3, 95%CI 0.1-0.8). The prediction model for total failure had an area under the ROC curve of 0.64 (95% CI 0.58-0.70). In women with postmenopausal bleeding, the failure rate of endometrial sampling is relatively high and is associated with nulliparity and advanced age. Endometrial thickness >12 mm decreased the chance of failure. A multivariable prediction model for total failure based on patient characteristics has a moderate capacity to discriminate between women at high or low risk of failure.


Inhibition of multiple trans-sarcolemmal cation flux pathways by dichlorobenzamil in cultured chick heart cells.
Dichlorobenzamil, an analog of amiloride, has been reported to inhibit Na-Ca exchange in sarcolemmal vesicles of guinea pig heart. To examine further the effect of the drug on Na-Ca exchange in intact cardiac cells and the pharmacological specificity of this action, we determined in cultured chick heart cells the effects of dichlorobenzamil on the following: contractile state, Nai-dependent Ca uptake, Ca uptake via slow Ca channels (defined as verapamil-inhibitable Ca uptake), Ca efflux via the sarcolemmal Ca pump, monovalent cation transport, and cellular Ca and Na content. Dichlorobenzamil produced a concentration-dependent decrease in the amplitude of cell motion (EC50 = 5 X 10(-7) M) and abolished the development of ouabain-induced rhythm disturbances and contracture. In normal or Na-loaded cells, dichlorobenzamil inhibited the Ca uptake rate, also in a concentration-dependent manner (EC50 = 6 X 10(-7) M). Dichlorobenzamil (6 X 10(-7) M) also caused a significant inhibition of the isoproterenol-induced elevation of Ca uptake. At 5 X 10(-5) M, dichlorobenzamil blocked completely Ca influx via slow Ca channels. Ca efflux rate was also reduced by dichlorobenzamil (EC50 = 10(-6) M). Replacement of Na with choline in the efflux medium to prevent Ca efflux via Na-Ca exchange did not alter the ED50 of the drug's inhibition of Ca efflux rate. Dichlorobenzamil caused concentration-dependent inhibition of sodium pump activity as judged by ouabain-sensitive 42K uptake (EC50 approximately 2 X 10(-6) M), and, at concentrations above 5 X 10(-7) M), produced an increase in steady state cellular Na content. These results indicate that dichlorobenzamil has several sites of action in intact heart cells and that the negative inotropic action of the drug is due, in part, to inhibition of Ca influx via both Na-Ca exchange and slow Ca channels.


Cholesterol Constrains the Antigenic Configuration of the Membrane-Proximal Neutralizing HIV-1 Epitope.
The envelope glycoprotein (Env) enables HIV-1 cell entry through fusion of host-cell and viral membranes induced by the transmembrane subunit gp41. Antibodies targeting the C-terminal sequence of the membrane-proximal external region (C-MPER) block the fusogenic activity of gp41 and achieve neutralization of divergent HIV-1 strains and isolates. Thus, recreating the structure that generates broadly neutralizing C-MPER antibodies during infection is a major goal in HIV vaccine development. Here, we have reconstituted a peptide termed CpreTM-TMD in a membrane environment. This peptide contains the C-MPER epitope and the minimum TMD residues required for the anchorage of the Env glycoprotein to the viral membrane. In addition, we have used antibody 10E8 variants to gauge the antigenic configuration attained by CpreTM-TMD as a function of the membrane cholesterol content, a functional determinant of the HIV envelope and liposome-based vaccines. Differential binding of the 10E8 variants and the trend of the IgG responses recovered from rabbits immunized with liposome-peptide formulations, suggested that cholesterol may restrict 10E8 accessibility to the C-MPER epitope. Our data ruled out the destabilization of the lipid bilayer architecture in CpreTM-TMD-containing membranes, and pointed to the perturbation of the helical conformation by lipid packing as the cause of the antigenic configuration loss induced by cholesterol. Overall, our results provide additional insights into the structural basis of the Env complex anchoring to membranes, and suggest new approaches to the design of effective immunogens directed against the near pan-neutralizing HIV-1 epitope C-MPER.


Second-messenger generation in PC12 cells. Interactions between cyclic AMP and Ca2+ signals.
Changes in cyclic AMP concentrations were studied in intact PC12 pheochromocytoma cells exposed to a variety of treatments. A marked increase was triggered by N-(L-2-phenylisopropyl)adenosine, the activator of an adenosine receptor, whereas a decrease (observed even after phosphodiesterase blockade) was induced by carbachol, working through a muscarinic receptor inhibited by the selective muscarinic blocker pirenzepine, only at high concentration (Ki 450 nM). A decrease in cyclic AMP was also induced by clonidine, an alpha 2-adrenergic-receptor agonist. Both the alpha 2-adrenergic and the muscarinic inhibitions were prevented by pretreatment of the cells with pertussis toxin, and were unaffected by the phorbol ester 12-O-tetradecanoylphorbol 13-acetate. The latter drug caused a decrease in the resting cyclic AMP concentrations, and a potentiation of the increase induced by adenosine-receptor activation. Except for clonidine, all these treatments were found to be effective in both growing PC12 cells and, although to a smaller degree, in cells that had stopped growing and had acquired a neuron-like phenotype after prolonged treatment with nerve growth factor (NGF). Neither forskolin (a direct activator of adenylate cyclase) nor the activation of adenosine and alpha-adrenergic receptors was able to modify the resting cytosolic Ca2+ concentration [Ca2+]i in PC12 cells. Likewise, the K+-induced [Ca2+]i transients were unchanged after these treatments, whereas the transients induced by carbachol through the activation of a muscarinic receptor highly sensitive to pirenzepine were moderately potentiated by forskolin (and, to a lesser degree, by the adenosine analogue) and attenuated by clonidine. These results characterize in further detail the spectrum and the mutual interrelationships of the intracellular signals induced by receptor activation in PC12 cells, also as a function of the NGF-induced differentiation.


Technical note: Resolution of spontaneous electromyographic discharge following disk-space distraction during lateral transpsoas interbody fusion.
The lateral transpsoas interbody fusion (LTIF) is an increasingly popular minimally invasive technique for lumbar interbody fusion. Although a posterior approach to the lumbar spine has traditionally been favored for the treatment of canal stenosis and neural foraminal stenosis, a growing body of evidence suggests that indirect decompression of the spinal canal and neural foramen can be achieved using a lateral transpsoas approach to the lumbar spine. We present 2 cases that may suggest a role for spontaneous electromyography (s-EMG) monitoring in assessing the adequacy of decompression during LTIF. The 2 cases presented in this technical note illustrate resolution of s-EMG firing during LTIF, following distraction across the disk space. Removal of the distracting device produced the return of s-EMG firing. Both of these cases were operated at the L2-3 level. In the first case, s-EMG firing was noted in the bilateral tibialis anterior leads. Resolution of EMG firing may suggest indirect decompression of the canal via ligamentotaxis as the L5 root traverses the L2-3 disk space. In the second case, s-EMG firing was noted in the left abductor hallucis and resolved with distraction of the L2-3 disk space. Again, this may be explained by canal decompression via ligamentotaxis as the S1 root traverses the L2-3 disk space. In both cases, distraction across the disk space resulted in resolution of s-EMG discharges-this correlated with an improvement in symptoms. These findings may suggest a role for s-EMG as a marker for adequacy of decompression in a select subset of patients undergoing LTIF. Further study is needed to determine if resolution of s-EMG is a useful measure of indirect decompression during LTIF.


Yogurt product intake and reduction of tooth loss risk in a Japanese community.
To evaluate the longitudinal association between yogurt product intake and oral health in a population-based study. This study included 1967 Japanese residents aged 40-79 years who underwent dental examinations in 2012. Among them, 1469 participants were followed up in 2017 for the incidence of tooth loss, which was defined as two or more teeth lost over 5 years. The intake of yogurt products, defined as yogurt and lactic acid beverages, was estimated using a semi-quantitative food frequency questionnaire. The composition of the salivary microbiota was evaluated. The Poisson regression model showed that a higher intake of yogurt products was negatively associated with the incidence of tooth loss (p for trend = .020), adjusted for potential confounding factors. Mediation analysis confirmed that periodontal condition partly mediated the effect of yogurt product intake on tooth loss, while dental caries experience did not. Additionally, we confirmed the association of a high intake of yogurt products with a low percentage of the salivary microbiota pattern, which was associated with poor oral health. These findings suggest that the intake of yogurt products is associated with a lower risk of tooth loss resulting from periodontal disease, probably via modulation of the oral microbiome composition.


Comment on Lopes et al. Adiposity Metabolic Consequences for Adolescent Bone Health. Nutrients 2022, 14, 3260.
This interesting report [...].


Vascular risk factors, incidence of MCI, and rates of progression to dementia.
To estimate prevalence, incidence, and rate of progression of mild cognitive impairment (MCI) to dementia and correlated vascular risk factors with incident MCI and its progression to dementia. The authors evaluated 2,963 individuals from the population-based sample of 5,632 subjects 65 to 84 years old, at the first (1992 to 1993) and second survey (1995 to 1996) of the Italian Longitudinal Study on Aging (ILSA), with a 3.5-year follow-up. Dementia, Alzheimer disease (AD), vascular dementia (VaD), other types of dementia, and MCI were classified using current clinical criteria. Among the 2,963 participants, 139 MCI patients were diagnosed at the first ILSA survey. During the 3.5-year follow-up, 113 new events of MCI were diagnosed with an estimated incidence rate of 21.5 per 1,000 person-years. We found a progression rate to dementia (all causes) of 3.8/100 person-years. Specific progression rates for AD, VaD, and other types of dementia were 2.3, 1.3, and 0.3/100 person-years. Furthermore, age was a risk factor for incident MCI (RR: 5.93, 95% CI: 3.17 to 11.10), while education was protective (RR: 0.06, 95% CI: 0.03 to 0.10), and serum total cholesterol evidenced a borderline nonsignificant trend for a protective effect. There was a nonsignificant trend for stroke as a risk factor of progression of MCI to dementia. In this population, among those who progressed to dementia, 60% progressed to AD and 33% to VaD. Vascular risk factors influence incident mild cognitive impairment and the rate of progression to dementia.


Facilitating and Complicating Factors in Coping with Fear of COVID-19.
The Covid-19 pandemic has affected almost all countries' people and affected them in many ways. Turkey has been one of the countries most affected by the Covid-19 pandemic. In this study, it is aimed to examine facilitating and complicating factors in coping with the fear of COVID-19. This study was conducted with 530 people (305 females, 225 males) living in different regions of Turkey and reached online via google e-forms. Sociodemographic information of the participants was collected, and the Fear of Covid-19 Scale (FCV-19S), Short Version of the Intolerance of Uncertainty Scale (IUS-12), The State-Trait Anxiety Inventory (STAI), and The World Health Organization Quality of Life (WHOQOL-BREF) scales were administered. All statistical analyzes were performed using IBM SPSS Statistics. T-test, One Way Anova and Linear Regression analysis were used to analyze the collected data. In this study, the participants reported that watching movies, reading books, and listening to music were the most important facilitating factors in coping with Fear of COVID-19. Covid-19 fear scores were analyzed in terms of some demographic variables. According to the results, there was no difference between COVID-19 fear scores in terms of gender, having a chronic disease or not, knowing someone diagnosed with Covid-19 in their immediate vicinity, and the region they lived in. we found that Prospective anxiety, inhibitory anxiety, state anxiety, and psychological health were significant predictors of Covid-19 fear. However, trait anxiety, physical health, social relationships and environment were not significant predictors of Covid-19 fear. All these variables together explained 25% of the variance in the model. Although this study has some limitations, it has an important place in the literature in revealing the facilitating and complicating factors in dealing with the fear of Covid -19. It mediates the provision of recommendations to policy makers and mental health professionals for providing psychological support services to individuals adversely affected by the COVID-19 pandemic process.


High resolution genetic mapping by genome sequencing reveals genome duplication and tetraploid genetic structure of the diploid Miscanthus sinensis.
We have created a high-resolution linkage map of Miscanthus sinensis, using genotyping-by-sequencing (GBS), identifying all 19 linkage groups for the first time. The result is technically significant since Miscanthus has a very large and highly heterozygous genome, but has no or limited genomics information to date. The composite linkage map containing markers from both parental linkage maps is composed of 3,745 SNP markers spanning 2,396 cM on 19 linkage groups with a 0.64 cM average resolution. Comparative genomics analyses of the M. sinensis composite linkage map to the genomes of sorghum, maize, rice, and Brachypodium distachyon indicate that sorghum has the closest syntenic relationship to Miscanthus compared to other species. The comparative results revealed that each pair of the 19 M. sinensis linkages aligned to one sorghum chromosome, except for LG8, which mapped to two sorghum chromosomes (4 and 7), presumably due to a chromosome fusion event after genome duplication. The data also revealed several other chromosome rearrangements relative to sorghum, including two telomere-centromere inversions of the sorghum syntenic chromosome 7 in LG8 of M. sinensis and two paracentric inversions of sorghum syntenic chromosome 4 in LG7 and LG8 of M. sinensis. The results clearly demonstrate, for the first time, that the diploid M. sinensis is tetraploid origin consisting of two sub-genomes. This complete and high resolution composite linkage map will not only serve as a useful resource for novel QTL discoveries, but also enable informed deployment of the wealth of existing genomics resources of other species to the improvement of Miscanthus as a high biomass energy crop. In addition, it has utility as a reference for genome sequence assembly for the forthcoming whole genome sequencing of the Miscanthus genus.


Critical behavior in the satisfiability of random boolean expressions.
Determining the satisfiability of randomly generated Boolean expressions with k variables per clause is a popular test for the performance of search algorithms in artificial intelligence and computer science. It is known that for k = 2, formulas are almost always satisfiable when the ratio of clauses to variables is less than 1; for ratios larger than 1, the formulas are almost never satisfiable. Similar sharp threshold behavior is observed for higher values of k. Finite-size scaling, a method from statistical physics, can be used to characterize size-dependent effects near the threshold. A relationship can be drawn between thresholds and computational complexity.


Antimicrobial activity of Cannabis sativa, Thuja orientalis and Psidium guajava leaf extracts against methicillin-resistant Staphylococcus aureus.
This study examined the antimicrobial activity of Cannabis sativa, Thuja orientalis and Psidium guajava against methicillin-resistant Staphylococcus aureus (MRSA) and used a standardized purification protocol to determine the presence and abundance of bioactive compounds in the leaf extracts. In vitro antimicrobial activities of the ethanolic extracts of C. sativa, T. orientalis and P. guajava were tested against MRSA. The presence of bioactive molecules in these three leaves was evaluated using biochemical assays and high-performance thin-layer chromatography (HPTLC). Resistance to methicillin, penicillin, oxacillin and cefoxitin was observed in each of the clinical and nonclinical MRSA isolates. However, they were still vulnerable to vancomycin. Used individually, the 50% extract of each plant leaf inhibited MRSA growth. A profound synergism was observed when C. sativa was used in combination with T. orientalis (1:1) and when P. guajava was used in combination with T. orientalis (1:1). This was shown by larger zones of inhibition. This synergism was probably due to the combined inhibitory effect of phenolics present in the leaf extracts (i.e., quercetin and gallic acid) and catechin, as detected by HPTLC. The leaf extracts of C. sativa, T. orientalis and P. guajava had potential for the control of both hospital- and community-acquired MRSA. Moreover, the inhibitory effect was enhanced when extracts were used in combination.


[Effects of 2 anabolizing substances with estrogenic action on the urethral muscle of the calf. Histochemical and morphometric study].
The testing of anabolizer utilization in cattle farming needs quick, sure and cheap detection techniques. The administration of oestrogen to cattle produces hypertrophy of the prostate, bulbourethral glands and urethral muscle. The aim of this study was to quantify the effect of the association of zeranol (an hormonomimetic drug acting as an oestrogen) and trembolone (a steroidic structure originating from testosterone) on the urethral muscle of bull calves which is easy to sample in the slaughter-house. An histoenzymological and morphometric study of the urethral muscle of 90 bull calves that had been treated showed considerable hypertrophy in transversal sections of the muscle fibers that was increased by more than 90% in the two main types of striated muscle fiber. The morphological method used is proposed for monitoring the meat of untreated bull calves, requested by a class of consumers.


Muscle-specific expression of hypoxia-inducible factor in human skeletal muscle.
Skeletal muscle is well known to exhibit a high degree of plasticity depending on environmental changes, such as various oxygen concentrations. Studies of the oxygen-sensitive subunit alpha of hypoxia-inducible factor-1 (HIF-1) are difficult owing to the large variety of functionally diverse muscle fibres that possess unique patterns of protein and gene expression, producing different capillarization and energy metabolism systems. In this work, we analysed HIF-1alpha mRNA and protein expression related to the fibre-type composition in untrained human skeletal muscle by obtaining muscle biopsies from triceps brachii (characterized by a high proportion of type II fibres), from soleus (characterized by a high proportion of type I fibres) and from vastus lateralis (characterized by an equal proportion of type I and II fibres). The hypothesis was that type I muscle fibres would have lower HIF-1alpha mRNA and protein owing to their higher oxidative capacity. We have shown, in normoxic conditions, a higher HIF-1alpha protein expression in predominantly oxidative muscles than in predominantly glycolytic muscles. However, the HIF-1alpha mRNA expression pattern was not in agreement with the HIF-1alpha protein level. Interestingly, none of the HIF-1alpha target genes, like the most studied angiogenic factor involved in muscle angiogenesis, vascular endothelial growth factor (VEGF), exhibited a muscle fibre-specific-related mRNA expression at rest in normoxia. However, soleus presented a significantly higher VEGF protein content than vastus lateralis and triceps muscle. In conclusion, we have shown that there are muscle-specific differences in HIF-1alpha and VEGF expression within human skeletal muscle at rest in normoxic conditions. Recent results, when combined with the findings described here, support a key role for HIF-1alpha for maintaining muscle homeostasis in non-hypoxic conditions.


Orbital solitary fibrous tumors: a multi-centered histopathological and immunohistochemical analysis with radiological description.
Solitary fibrous tumors (SFT), formerly called hemangiopericytoma, are rare tumors derived from mesenchymal cells originally described in the pleura, but these tumors may affect extraserosal tissues including the lacrimal gland and orbit. Conduct a multi-centered clinical, radiological and histopathological analysis of 17 orbital SFT cases. A retrospective case series. Three eye centers in two countries. The data collected from the charts of 17 adult patients presenting with tissue diagnosis of orbital hemangiopericytoma or SFT from January 2003 to December 2018 included demographics, clinical imaging and histopathological information including immunohistochemical (IHC) characteristics. The demographic characteristics, clinical presentation, and histopathological patterns or variants of SFT were analyzed. 17 adult patients. Mean age was 45 years (range 23-80 years). Male to female ratio was 3:1. The right eye was affected in 12 (70.5%) patients. Commonest presentation was proptosis in 13/17 (76% of patients). Other symptoms were impaired motility (29%) and ptosis (11%). Lesions mostly affected the medial orbit (35%), then orbital apex in 11%. The histopathological classic pattern-less variant was the commonest. One case with aggressive behavior, multiple recurrences and atypical features was encountered. Immunohistochemical (IHC) markers used included CD34 expression in all cases, Bcl-2 expression in 10/11, CD99 in 9/9 and Vimentin in 4/4. STAT6 was used in 2 cases. SFTs are rare tumors affecting the orbit in both genders equally in their mid-forties, but showed male predominance in our analysis with a predominant classic histopathological pattern. Tissue diagnosis is essential and requires IHC studies for confirmation. Sample size is relatively small owing to the rarity of this tumor in the orbit. None.


Metabolic Signature of Dietary Iron Overload in a Mouse Model.
Iron is an essential co-factor for several metabolic processes, including the Krebs cycle and mitochondrial oxidative phosphorylation. Therefore, maintaining an appropriate iron balance is essential to ensure sufficient energy production and to avoid excessive reactive oxygen species formation. Iron overload impairs mitochondrial fitness; however, little is known about the associated metabolic changes. Here we aimed to characterize the metabolic signature triggered by dietary iron overload over time in a mouse model, where mice received either a standard or a high-iron diet. Metabolic profiling was assessed in blood, plasma and liver tissue. Peripheral blood was collected by means of volumetric absorptive microsampling (VAMS). Extracted blood and tissue metabolites were analyzed by liquid chromatography combined to high resolution mass spectrometry. Upon dietary iron loading we found increased glucose, aspartic acid and 2-/3-hydroxybutyric acid levels but low lactate and malate levels in peripheral blood and plasma, pointing to a re-programming of glucose homeostasis and the Krebs cycle. Further, iron loading resulted in the stimulation of the urea cycle in the liver. In addition, oxidative stress was enhanced in circulation and coincided with increased liver glutathione and systemic cysteine synthesis. Overall, iron supplementation affected several central metabolic circuits over time. Hence, in vivo investigation of metabolic signatures represents a novel and useful tool for getting deeper insights into iron-dependent regulatory circuits and for monitoring of patients with primary and secondary iron overload, and those ones receiving iron supplementation therapy.


Lithographically-featured photonic microparticles of colloidal assemblies.
We have described a new and promising strategy for the fabrication of composite and porous photonic crystal microparticles that combines the self-assembly of colloidal particles with photolithography techniques. We fabricated silica/SU-8 composite microparticles with photonic bandgaps via four steps: (1) deposition of the silica colloidal crystals on the photoresist, (2) embedding of the colloidal crystals in the photoresist, (3) UV exposure through a photomask and subsequent development, and (4) release of the microparticles from the substrate. Embedding was performed above the glass transition temperature (T(g)) of uncrosslinked SU-8. At such temperatures, capillary forces on the silica particles facilitate the migration of colloidal crystals in the SU-8 matrix. Particle migration ceased when the top colloidal crystal layer was trapped at the interface between air and SU-8. In addition, we also prepared porous microparticles with an inverse opaline structure by dissolving the embedded silica particles from the composite structures. The porous microparticles showed enhanced reflectivity at the bandgap position due to the large refractive index contrast. The bandgap position of the microparticles was controlled by the size of the silica particles, which determined the lattice constant. Bilayered composite and porous microparticles with two distinct photonic bandgaps were also prepared by sequential deposition of colloidal crystals composed of two differently sized silica particles.


Global Trends in Cannabis and Cannabidiol Research from the Year 1940 to 2019.
Legalization of Cannabis in countries, like Canada, and global demand for non-hallucinating chemical components, such as Cannabidiols (CBD), have stimulated the increased interest from academics, industry, and regulatory agencies. Subsequent research publications in scientific journals in this field are expected to grow rapidly. However, there have been few research reviews that have quantified patterns in research publications concerning cannabis, nor a literature-based perspective on the historical development, current status, and future direction of cannabis research. Here, a bibliometric analysis is performed to address this gap in the scientific literature. A total of 1167 relevant articles (Supplementary file 1) were screened and analyzed using three software tools: HistCite, CiteSpace, and Bibliometric Online Analysis Platform. The performances of relevant countries, institutions, authors, and journals were presented, and the evolutionary trends of different categories were revealed. The historical development of cannabis and CBD research can be clearly divided into three stages, which focus on the chemistry, pharmacology, and molecular biology aspects of Cannabis sativa in general and then a focus on CBD related publications. A timeline was drawn to highlight the major trends in the literature, including scientific discoveries. In the end, several suggestions for future research directions in this field are provided.


Steps toward knowledge-based machine translation.
This paper considers the possibilities for knowledge-based automatic text translation in the light of recent advances in artificial intelligence. It is argued that competent translation requires some reasonable depth of understanding of the source text, and, in particular, access to detailed contextual information. The following machine translation paradigm is proposed. First, the source text is analyzed and mapped into a language-free conceptual representation. Inference mechanisms then apply contextual world knowledge to augment the representation in various ways, adding information about items that were only implicit in the input text. Finally, a natural-language generator maps appropriate sections of the language-free representation into the target language. We discuss several difficult translation problems from this viewpoint with examples of English-to-Spanish and English-to-Russian translations; and illustrate possible solutions as embodied in a computer understander called SAM, which reads certain kinds of newspaper stories, then summarizes or paraphrases them in a variety of languages.


Diseases of the eye of farmed shrimp Penaeus monodon.
Lesions were found in the eyes of cultured shrimp Penaeus monodon that displayed non-specific signs of disease, including lethargy, dark pigmentation, brown gills, empty midgut, anorexia, white tail muscle, necrosis of uropods and fouled cuticle. Eye lesions were associated with sexual development in moribund shrimp in at least 1 disease event. Suppurative inflammation, granuloma and malacia were observed in histological examination of the eye and the causative agents of lesions appear to be Vibrio spp. and a rod-shaped virus (similar to Lymphoid Organ Virus, Gill-Associated Virus [GAV] and Yellow-Head Virus). Suppurative inflammation was characterised by edema, infiltration of haemocytes and local sites of abscesses. Eyes with granuloma usually appeared white in pond-side examinations, and histology showed that fibrous tissue replaced ommatidia, ganglia and internal structures of the eye. Malacia of the eye was characterised by necrosis of nervous tissue, vacuolation and vascular proliferation in the medulla ganglia. Levels of presumptive Vibrionaceace were high in moribund specimens and Gram-negative rods were observed in some specimens as free particles in the interstitial fluid and haemolymph in the eye. Transmission electron microscopy showed that nerve cells in the fasciculated zone (near the basement membrane) contained cytoplasmic vesicles (1 to 3 microm in diameter) with particles (15 to 26 nm in diameter) and rod-shaped nucleocapsids. The rods were similar to those of GAV and were 130 to 260 nm long, 10 to 16 nm in diameter and had helical symmetry with a screw-like thread (2.4 to 3.5 nm pitch). Also, unidentified enveloped virions, averaging 74 nm in diameter, were observed in cytoplasmic vesicles in the fasciculated zone. In conclusion, it is suggested that bacterial and viral infections of the eye could result in impaired neuroendocrine functions, which may cause a range of clinical signs of disease.


[The presence of medications in the water cycle].
Medications and radiographic contrast dyes are sometimes detected in surface waters, ground water and drinking water; these have proven detrimental effects on organisms living in such waters The concentration of medications found in drinking water is at least a thousand times below their minimum therapeutic dosages. In humans, the long-term effects of daily exposure to low dosages of medications and 'mixture toxicity' is not known; based on the concentrations and substance toxicity, it is presumed that the risk is nil.. Physicians can play their part in controlling the problem of medications becoming part of the water cycle by taking this into account when prescribing medications. Users can make a difference by handling their medications with care and by returning all unused portions to the pharmacy. The pharmaceutical industry can also do its part by taking degradability, options for removal and the environmental effects of medications into account during their stages of development.


Advanced Cardiovascular Sonographer: a proposal of the American Society of Echocardiography Advanced Practice Sonographer Task Force.
Echocardiographic examinations require a well-trained and competent sonographer to obtain proper anatomic and physiologic data to establish an accurate diagnosis for clinical decision-making and patient management. Although the formal education and training of cardiovascular sonographers are evolving, many entry-level and staff sonographers may not have sufficient practical or clinical knowledge of the necessary components of the echocardiographic study for the individual patient's clinical presentation. In many clinical settings, echocardiograms are read after the patient has left the laboratory. Thus, there is a role for a sonographer who can practice at an advanced level in a cardiovascular ultrasound laboratory to ensure a proper echocardiographic examination is performed on every patient. In this setting, an Advanced Cardiovascular Sonographer (ACS) would be able to review the indication for and quality of the examination. If additional images were needed, the ACS would assist the sonographer in obtaining these images, which would lead to the performance of a complete and fully diagnostic examination before the patient had left the echocardiography laboratory. In clinical practice, the quality of the examinations performed would improve, advancements in echocardiographic methods could be taught and incorporated into daily practice, and patients would be better served. The present report is a proposal from the American Society of Echocardiography Advanced Practice Task Force that identifies the potential of cardiac sonographers to achieve the ACS level.


Toward efficient electrodes for a high-performance fast-charge Li-ion battery: molecular dynamics simulation and DFT calculations.
Due to the increasing demand for electrochemical energy storage, rechargeable lithium-ion batteries (LIBs) are gaining more and more attention. However, much research still needs to be conducted to enhance their cycling and storage capacity. Recently, computational studies have provided valuable information for LIB development, which is very difficult and expensive to obtain experimentally. In this study, molecular dynamics (MD) simulation and first-principles calculations are performed to investigate the potential of a Cu-BHT MOF and phosphorene as the cathode and anode, respectively. An external electrical field is applied to simulate the charging process and study lithium-ion behavior during migration from the cathode to the anode in an electrolyte. Time and space-dependent variables such as energy, radial distribution function, mean square displacement (MSD), density, and so on have been used to evaluate the studied system. The MSD calculations showed that there are two different regimes in the MSD curves of Li-ions; diffusion and cage. In the designed LIB, the cathode has a better performance in the presence of a high electric field, whereas under an external electric field of 1.5 V Å-1, more lithium ions move from the cathode to the anode. By using first-principles calculations the lithium insertion in phosphorene and Cu-BHT is studied in various configurations and concentrations. The obtained results indicated that the adsorption energy of lithium on the cathode in the most stable configuration is -3.21 eV which is enough to prevent the clustering effect. Furthermore, the interaction of Li with phosphorene is strong enough and forms a stable complex. It is found that by insertion of Li into the anode the band gap is decreased which indicates the possibility of fast charging of LIBs. Investigation of different concentrations of ions reveals that the Li-Li repulsive interactions lead to a decrease in the adsorption energy of Li with the anode and cathode. The results of this study provide an in-depth insight into LIBs.


Effect of pH on bronchial response to inhaled histamine.
In order to investigate the effect of pH on bronchial responsiveness to inhaled histamine, 15 subjects with non-specific bronchial hyperreactivity performed two histamine inhalation tests, one with unbuffered, and the other with buffered histamine acid phosphate solutions. The unbuffered histamine solutions were prepared with 0.9% sterile saline and had a pH range from 4.3 to 7.3, while the buffered histamine solutions were prepared with a phosphate buffer and had a pH range of 6.5 to 7.4. The two histamine inhalation tests were similar in all other regards. The geometric mean histamine provocation concentration required to produce a 20% reduction in FEV1 (PC20) was significantly lower for the unbuffered histamine (1.33 mg/ml) than for the buffered histamine (1.67 mg/ml), p less than 0.05. The two PC20s differed by less than one doubling dilution, the range of reproducibility of the test, in 12 of the 15 subjects. The pH effect was only noted when the pH of the histamine solutions was below five (histamine concentrations from one to eight mg/ml). We conclude that the acid pH of higher concentrations of histamine acid phosphate solutions has a slight but significant enhancing effect on the bronchial responsiveness to inhaled histamine.


Oxygen produced by cyanobacteria in simulated Archaean conditions partly oxidizes ferrous iron but mostly escapes-conclusions about early evolution.
The Earth has had a permanently oxic atmosphere only since the great oxygenation event (GOE) 2.3-2.4 billion years ago but recent geochemical research has revealed short periods of oxygen in the atmosphere up to a billion years earlier before the permanent oxygenation. If these "whiffs" of oxygen truly occurred, then oxygen-evolving (proto)cyanobacteria must have existed throughout the Archaean aeon. Trapping of oxygen by ferrous iron and other reduced substances present in Archaean oceans has often been suggested to explain why the oxygen content of the atmosphere remained negligible before the GOE although cyanobacteria produced oxygen. We tested this hypothesis by growing cyanobacteria in anaerobic high-CO2 atmosphere in a medium with a high concentration of ferrous iron. Microcystins are known to chelate iron, which prompted us also to test the effects of microcystins and nodularins on iron tolerance. The results show that all tested cyanobacteria, especially nitrogen-fixing species grown in the absence of nitrate, and irrespective of the ability to produce cyanotoxins, were iron sensitive in aerobic conditions but tolerated high concentrations of iron in anaerobicity. This result suggests that current cyanobacteria would have tolerated the high-iron content of Archaean oceans. However, only 1 % of the oxygen produced by the cyanobacterial culture was trapped by iron, suggesting that large-scale cyanobacterial photosynthesis would have oxygenated the atmosphere even if cyanobacteria grew in a reducing ocean. Recent genomic analysis suggesting that ability to colonize seawater is a secondary trait in cyanobacteria may offer a partial explanation for the sustained inefficiency of cyanobacterial photosynthesis during the Archaean aeon, as fresh water has always covered a very small fraction of the Earth's surface. If oxygenic photosynthesis originated in fresh water, then the GOE marks the adaptation of cyanobacteria to seawater, and the late-Proterozoic increase in oxygen concentration of the atmosphere is caused by full oxidation of the oceans.


Cicatricial pemphigoid (Brunsting-Perry type). Case report and immunofluorescence findings.
We describe clinical and immunofluorescence findings of a patient with Brunsting-Perry-type cicatricial pemphigoid. Direct immunofluorescence showed tissue-fixed basement membrane zone antibodies similar to those characteristic of bullous pemphigoid. Circulating antibodies to the basement membrane zone were not found. Brunsting-Perry-type cicatricial pemphigoid probably represents a clinical variation midway in the cicatricial pemphigoid-bullous pemphigoid spectrum of disease. Management with intralesional corticosteroids was successful in controlling the skin lesions.


Inhibition of nitrogenase-catalyzed NH3 formation by H2.
We have investigated the inhibition by H2 (D2) of NH3 formation by nitrogenase from Klebsiella pneumoniae and have confirmed that the inhibition is competitive vs. N2. D2 inhibits NH3 formation by diverting nitrogenase from production of NH3 to production of HD (one electron per HD). By careful exclusion of N2 from the reaction mixture, we have been able to place an upper limit on N2-independent HD formation by nitrogenase, under 1 atm of D2, at 1% of the total electron flux. Formation of NH3 and formation of HD were inhibited identically by CO. We observed that as the ratio of dinitrogenase to dinitrogenase reductase is increased, the ratio of HD formed to NH3 formed rises, and D2 becomes a stronger inhibitor of N2 reduction. This may be caused in part by an accompanying increase that is observed in the Km of nitrogenase for N2. We propose a model for D2 inhibition of NH3 formation in which D2 and N2 complete for the same form of nitrogenase. According to our proposal, when N2 reacts with nitrogenase, either N2 reduction proceeds to completion if H2 (D2) is absent or, if D2 already is bound to nitrogenase, N2 reduction is aborted and two molecules of HD are produced at the net expense of one electron per HD. Key consequences of the model are that it predicts that H2 (D2) is a competitive inhibitor of NH3 formation and that the apparent Km (N2) for formation of HD and NH3 may differ.


Shark cartilage, cancer and the growing threat of pseudoscience.
The promotion of crude shark cartilage extracts as a cure for cancer has contributed to at least two significant negative outcomes: a dramatic decline in shark populations and a diversion of patients from effective cancer treatments. An alleged lack of cancer in sharks constitutes a key justification for its use. Herein, both malignant and benign neoplasms of sharks and their relatives are described, including previously unreported cases from the Registry of Tumors in Lower Animals, and two sharks with two cancers each. Additional justifications for using shark cartilage are illogical extensions of the finding of antiangiogenic and anti-invasive substances in cartilage. Scientific evidence to date supports neither the efficacy of crude cartilage extracts nor the ability of effective components to reach and eradicate cancer cells. The fact that people think shark cartilage consumption can cure cancer illustrates the serious potential impacts of pseudoscience. Although components of shark cartilage may work as a cancer retardant, crude extracts are ineffective. Efficiencies of technology (e.g., fish harvesting), the power of mass media to reach the lay public, and the susceptibility of the public to pseudoscience amplifies the negative impacts of shark cartilage use. To facilitate the use of reason as the basis of public and private decision-making, the evidence-based mechanisms of evaluation used daily by the scientific community should be added to the training of media and governmental professionals. Increased use of logical, collaborative discussion will be necessary to ensure a sustainable future for man and the biosphere.


Medically treated splenic abscess due to Brucella melitensis.
Brucellosis may lead to complications that affect different organ systems, including the liver and spleen. In acute disease, hepatosplenic abscess is a rare complication. We report herein a woman with splenic abscess due to acute Brucella melitensis infection who was successfully treated with antibiotics alone.


Primary prevention of diabetes: what can be done and how much can be prevented?
Although it is widely believed that type 2 diabetes mellitus is the result of a complex interplay between genetic and environmental factors, compelling evidence from epidemiologic studies indicates that the current worldwide diabetes epidemic is largely due to changes in diet and lifestyle. Prospective cohort studies and randomized clinical trials have demonstrated that type 2 diabetes can be prevented largely through moderate diet and lifestyle modifications. Excess adiposity is the most important risk factor for diabetes, and thus, maintaining a healthy body weight and avoiding weight gain during adulthood is the cornerstone of diabetes prevention. Increasing physical activity and reducing sedentary behaviors such as prolonged TV watching are important both for maintaining body weight and improving insulin sensitivity. There is increasing evidence that the quality of fat and carbohydrate plays a more important role than does the quantity, and thus, public health strategies should emphasize replacing saturated and trans fats with unsaturated fats and replacing refined grain products with whole grains. Recent studies have also suggested a potential role for coffee, dairy, nuts, magnesium, and calcium in preventing diabetes. Overall, a healthy diet, together with regular physical activity, maintenance of a healthy weight, moderate alcohol consumption, and avoidance of sedentary behaviors and smoking, could nearly eliminate type 2 diabetes. However, there is still a wide gap between what we know and what we practice in the field of public health; how to narrow that gap remains a major public health challenge.


[The feigned release of cell enzymes. Distribution and transport of cell enzymes within the extracellular space. I (author's transl)].
A sudden increase of enzyme activities in plasma is not necessarily due to a release of enzymes from damaged cells. Three experimental models were used to demonstrate that acute alterations of enzyme activities, as much as +/- 15%, can be caused by fluid-shifts between the intra- and extravascular compartments. Venous occlusion of the forearm by tourniquet produces an increase of the intravascular hydrostatic pressure and subsequently results in a decrease of the plasma volume distal to the tourniquet. Because enzyme molecules are not freely diffusible across the capillary membrane the enzymatic activity increases proportionally to the decrease of plasma volume. Changes in the body posture are accompanied by changes in plasma volume and similarly by alterations in the concentration of plasma-proteins and by alterations in intravascular enzyme activities. Increased enzyme activities in plasma during strenuous physical effort are due chiefly to a concentration of macromolecules within the intravascular space because of a decrease in plasma volume and not to a release of enzymes from hypoxic muscle cells. During recovery after termination of the exercise there is a second and longer lasting increase in enzyme activities in plasma which could be related to a release of enzymes from injured cells. It is suggested that some of these changes could be due to an increase in lymph flow and thereby an increasing transport of enzymes from the interstitial to the intravascular compartment.


Percutaneous nephrostomy with extensions of the technique: step by step.
Minimally invasive therapy in the urinary tract begins with renal access by means of percutaneous nephrostomy. Indications for percutaneous nephrostomy include urinary diversion, treatment of nephrolithiasis and complex urinary tract infections, ureteral intervention, and nephroscopy and ureteroscopy. Bleeding complications can be minimized by entering the kidney in a relatively avascular zone created by branching of the renal artery. The specific site of renal entry is dictated by the indication for access with consideration of the anatomic constraints. Successful percutaneous nephrostomy requires visualization of the collecting system for selection of an appropriate entry site. The definitive entry site is then selected; ideally, the entry site should be subcostal and lateral to the paraspinous musculature. Small-bore nephrostomy tracks can be created over a guide wire coiled in the renal pelvis. A large-diameter track may be necessary for percutaneous stone therapy, nephroscopy, or antegrade ureteroscopy. The most common extension of percutaneous nephrostomy is placement of a ureteral stent for treatment of obstruction. Transient hematuria occurs in virtually every patient after percutaneous nephrostomy, but severe bleeding that requires transfusion or intervention is uncommon. In patients with an obstructed urinary tract complicated by infection, extensive manipulations pose a risk of septic complications.


Effects of amphotericin B on Aspergillus flavus clinical isolates with variable susceptibilities to the polyene in an experimental model of systemic aspergillosis.
The aim of the present study was to evaluate the effects of amphotericin B (AMB) on clinical isolates of Aspergillus flavus. MICs of both standard AMB and liposomal AMB (L-AMB) were determined using a broth dilution method for seven isolates of A. flavus. AMB MICs were also determined using the Etest. The activity of the polyene was then investigated in a murine model of systemic aspergillosis in which animals were infected intravenously, treated intravenously with several doses of the polyene (1-10 mg/kg/day) and observed for survival. Broth dilution AMB, broth dilution L-AMB and Etest AMB MICs ranged from 0.5 to 2.0 mg/L, 0.06 to >16 mg/L and 1.0 to >32 mg/L, respectively. There were two isolates for which all doses were effective at prolonging the survival. Their AMB MICs were ≤1.0 mg/L, regardless of the method/drug formulation utilized for testing. There were four isolates for which no regimen was effective. Their broth dilution AMB, broth dilution L-AMB and Etest AMB MICs ranged from 1.0 to 2.0 mg/L, 0.06 to >16 mg/L and 2.0 to >32 mg/L, respectively. There was one isolate for which only L-AMB given at 10 mg/kg/day was effective; broth dilution MICs of AMB and L-AMB were 0.5 mg/L, while the Etest MIC of AMB was 2.0 mg/L. Our data indicate that not all isolates of A. flavus should be considered resistant to AMB. The Etest represented the in vitro method that best correlated with the experimental infection. Finally, a clinical isolate showing an MIC ≥2.0 mg/L may be reasonably considered resistant in vivo to any dose/formulation of the polyene.


Human platelet stimulation by acetyl glyceryl ether phosphorylcholine.
Acetyl glyceryl ether phosphorylcholine (AGEPC) induced dose-dependent platelet aggregation and release of [3H]serotonin and platelet factor 4 in citrated human platelet-rich plasma. ADP scavengers or indomethacin prevented irreversible platelet aggregation responses induced by 0.2 microM AGEPC but had no effect upon platelet secretion; prostacyclin inhibited AGEPC-induced aggregation and secretion. EDTA or EGTA inhibited AGEPC-induced aggregation but had no effect on platelet secretion.


[A rapid method for cutting arthropod tissue sections in paraffin].
Using heat and agitation as modifying agents the time of processing up to paraffin embedding was considerably decreased in a method for obtaining arthropod tissue sections. The new procedure is flexible thus enabling its use in different species as well as its adaptation to different availabilities of equipment and time for its development.


A cohort-based study of host gene expression: tumor suppressor and innate immune/inflammatory pathways associated with the HIV reservoir size.
The major barrier to an HIV cure is the HIV reservoir: latently-infected cells that persist despite effective antiretroviral therapy (ART). There have been few cohort-based studies evaluating host genomic or transcriptomic predictors of the HIV reservoir. We performed host RNA sequencing and HIV reservoir quantification (total DNA [tDNA], unspliced RNA [usRNA], intact DNA) from peripheral CD4+ T cells from 191 ART-suppressed people with HIV (PWH). After adjusting for nadir CD4+ count, timing of ART initiation, and genetic ancestry, we identified two host genes for which higher expression was significantly associated with smaller total DNA viral reservoir size, P3H3 and NBL1, both known tumor suppressor genes. We then identified 17 host genes for which lower expression was associated with higher residual transcription (HIV usRNA). These included novel associations with membrane channel (KCNJ2, GJB2), inflammasome (IL1A, CSF3, TNFAIP5, TNFAIP6, TNFAIP9, CXCL3, CXCL10), and innate immunity (TLR7) genes (FDR-adjusted q<0.05). Gene set enrichment analyses further identified significant associations of HIV usRNA with TLR4/microbial translocation (q = 0.006), IL-1/NRLP3 inflammasome (q = 0.008), and IL-10 (q = 0.037) signaling. Protein validation assays using ELISA and multiplex cytokine assays supported these observed inverse host gene correlations, with P3H3, IL-10, and TNF-α protein associations achieving statistical significance (p<0.05). Plasma IL-10 was also significantly inversely associated with HIV DNA (p = 0.016). HIV intact DNA was not associated with differential host gene expression, although this may have been due to a large number of undetectable values in our study. To our knowledge, this is the largest host transcriptomic study of the HIV reservoir. Our findings suggest that host gene expression may vary in response to the transcriptionally active reservoir and that changes in cellular proliferation genes may influence the size of the HIV reservoir. These findings add important data to the limited host genetic HIV reservoir studies to date.


Regulation of viral transcription in cells infected with iododeoxyuridine-substituted simian virus 40 as a model for the activation by iododeoxyuridine of latent viral genomes.
5-Iododeoxyuridine (IdUrd) induces the expression of viruses in a variety of cell lines that harbor latent viral genomes. Moreover, IdUrd stimulates cellular as well as viral RNA synthesis in certain cells. In order to understand better the action of IdUrd on RNA metabolism, we have examined viral RNA synthesis in monkeys cell infected with IdUrd-substituted simian virus 40 (SV40). Extensively substituted SV40, in which 18 to 35% of the thymidine residues were substituted by IdUrd, was 100-fold less viable (by plaque analysis) than was unsubstituted SV40, although the substituted virus induced 30 to 50% as much viral-specific RNA as did the unsubstituted virus. In contrast, SV40, containing only 10 to 15% IdUrd, substitution was almost as viable as unsubstituted virus, and the substituted SV40 induced 5-fold more viral-specific RNA, as well as longer viral messenger RNA transcripts, than did the unsubstituted virus. These results suggest that the lightly substituted, mutagenized SV40 genome may produce defective proteins which fall to regulate their own transcription. Cellular DNA into which halogenated pyrimidines have been incorporated may also induce the synthesis of defective regulatory proteins, including cellular repressors of transcription which normally maintain the latent state of integrated viral genomes.


Smoking May Increase Postoperative Opioid Consumption in Patients Who Underwent Distal Gastrectomy With Gastroduodenostomy for Early Stomach Cancer: A Retrospective Analysis.
Although nicotine has an analgesic effect, the incidence and severity of chronic pain is higher in smokers than nonsmokers. Acute pain is more intense in smokers during the perioperative period. This study evaluated whether smokers require higher doses of opioid to reduce pain when they undergo surgery. A retrospective review of 236 patients who had intravenous patient-controlled analgesia after distal gastrectomy with gastroduodenostomy between October 2013 and September 2014 was performed to analyze the difference in postoperative opioid requirements between smokers and nonsmokers. Total opioid consumption was observed from the day of operation to postoperative day 2. Patients were grouped into smokers (N=117) and nonsmokers (N=119) for comparison. Simple and multiple regression analyses were performed to identify predictors of postoperative opioid requirements. Opioid consumption by male smokers was higher than nonsmokers. Multiple regression analysis showed that age, smoking, and amount of intraoperative remifentanil were the only significant factors for postoperative opioid requirements. Our results suggest that smokers undergoing distal gastrectomy with gastroduodenostomy required more opioid than nonsmokers for postoperative pain. Old age, smoking status, and increment of remifentanil use seemed to be predictors of postoperative opioid consumption.


Ligand-receptor binding affinities from saturation transfer difference (STD) NMR spectroscopy: the binding isotherm of STD initial growth rates.
The direct evaluation of dissociation constants (K(D)) from the variation of saturation transfer difference (STD) NMR spectroscopy values with the receptor-ligand ratio is not feasible due to the complex dependence of STD intensities on the spectral properties of the observed signals. Indirect evaluation, by competition experiments, allows the determination of K(D), as long as a ligand of known affinity is available for the protein under study. Herein, we present a novel protocol based on STD NMR spectroscopy for the direct measurements of receptor-ligand dissociation constants (K(D)) from single-ligand titration experiments. The influence of several experimental factors on STD values has been studied in detail, confirming the marked impact on standard determinations of protein-ligand affinities by STD NMR spectroscopy. These factors, namely, STD saturation time, ligand residence time in the complex, and the intensity of the signal, affect the accumulation of saturation in the free ligand by processes closely related to fast protein-ligand rebinding and longitudinal relaxation of the ligand signals. The proposed method avoids the dependence of the magnitudes of ligand STD signals at a given saturation time on spurious factors by constructing the binding isotherms using the initial growth rates of the STD amplification factors, in a similar way to the use of NOE growing rates to estimate cross relaxation rates for distance evaluations. Herein, it is demonstrated that the effects of these factors are cancelled out by analyzing the protein-ligand association curve using STD values at the limit of zero saturation time, when virtually no ligand rebinding or relaxation takes place. The approach is validated for two well-studied protein-ligand systems: the binding of the saccharides GlcNAc and GlcNAcbeta1,4GlcNAc (chitobiose) to the wheat germ agglutinin (WGA) lectin, and the interaction of the amino acid L-tryptophan to bovine serum albumin (BSA). In all cases, the experimental K(D) measured under different experimental conditions converged to the thermodynamic values. The proposed protocol allows accurate determinations of protein-ligand dissociation constants, extending the applicability of the STD NMR spectroscopy for affinity measurements, which is of particular relevance for those proteins for which a ligand of known affinity is not available.


Linear Response Equations Revisited: A Simple and Efficient Iterative Algorithm.
We present an algorithm to solve the linear response equations for Hartree-Fock, Density Functional Theory, and the Multiconfigurational Self-Consistent Field method that is both simple and efficient. The algorithm makes use of the well-established symmetric and antisymmetric combinations of trial vectors but further orthogonalizes them with respect to the scalar product induced by the response matrix. This leads to a standard, symmetric block eigenvalue problem in the expansion subspace that can be solved by diagonalizing a symmetric, positive definite matrix half the size of the expansion space. Numerical tests showed that the algorithm is robust and stable.


Effects of foliar herbivory by insects on the fitness of Raphanus raphanistrum: damage can increase male fitness.
Generally, effects of herbivory on plant fitness have been measured in terms of female reproductive success (seed production). However, male plant fitness, defined as the number of seeds sired by pollen, contributes half of the genes to the next generation and is therefore crucial to the evolution of natural plant populations. This is the first study to examine effects of insect herbivory on both male and female plant reproductive success. Through controlled field and greenhouse experiments and genetic paternity analysis, we found that foliar damage by insects caused a range of responses by plants. In one environment, damaged plants had greater success as male parents than undamaged plants. Neither effects on pollen competitive ability nor pollinator visitation patterns could explain the greater siring success of these damaged plants. Success of damaged plants as male parents appeared to be due primarily to changes in allocation to flowers versus seeds after damage. Damaged plants produced more flowers early in the season, but not more seeds, than undamaged plants. Based on total seed production, male fitness measures from the first third of the season, and flower production, we estimated that damaged and undamaged plants had equal total reproductive success at the end of the season in this environment. In a second, richer environment, damaged and undamaged plants had equal male and female plant fitness, and no traits differed significantly between the treatments. Equal total reproductive success may not be ecologically or evolutionarily equivalent if it is achieved differentially through male versus female fitness. Genes from damaged plants dispersed through pollen may escape attack from herbivores, if such attack is correlated spatially from year to year.


The costs and utility of imaging in evaluating dizzy patients in the emergency room.
To determine the usefulness and the costs of computed tomography (CT) and magnetic resonance imaging (MRI) in the evaluation of patients with dizziness in the emergency department (ED). Retrospective chart review. Charts of patients with a specific health maintenance insurance plan presenting with dizziness and vertigo to a large health system's ED between January 2008 and January 2011 were reviewed. Patient demographics, signs/symptoms, and CT and MRI results were assessed. CT and MRI charges were determined based on positive versus unremarkable findings. Data analysis included stepwise logistic regressions. Of 1681 patients identified, 810 (48%) received CT brain/head scan totaling $988,200 in charges. Of these, only 0.74% yielded clinically significant pathology requiring intervention. However, 12.2% of MRI studies yielded discovery of significant abnormalities. Logistic regression analysis revealed that older patients (P = .001) were more likely to receive a CT scan. In the 3-year period studied, CT scans for ED patients with dizziness and vertigo yielded a low predictive value for significant pathology. These data reveal a great opportunity for cost savings by developing stricter guidelines for ordering CT scans for this set of ED patients. The use of MRI in all cases of dizziness was found to be neither practical nor useful. However, appropriately directed MRI of the brain is recommended in patients with dizziness and other neurological signs or symptoms.


Isokinetic Training Program to Improve the Physical Function and Muscular Performance of an Individual with Partial Injury of the Medial Meniscus: A Case Report.
One of the best alternatives for the treatment of meniscal injuries in relation to surgical procedures, is exercise. This case report aimed to describe the effects of isokinetic training and a neuromuscular/proprioceptive exercise program on muscle performance and physical function in an individual after a rupture of the posterior horn of the medial meniscus. Case report. A 40-year-old man injured his right knee during a soccer match, with a partial lesion of the medial meniscus confirmed by magnetic resonance imaging. He completed an isokinetic training program in addition to exercises that targeted proprioception (22 sessions, 11 weeks) to improve physical function and performance, which were assessed before and after treatment and at a six-month follow-up. An individual with similar anthropometric characteristics was chosen to be used as a control for understanding the patient's assessment values. Muscular performance of the knee flexors and extensors was evaluated isokinetically using the Biodex System-4 in a concentric mode at angular velocities of 60, 120, and 300 °/s . The main results indicated that after 11 weeks, the peak torque normalized to body mass (PT/BM), at 60 °/s of the knee extensors remained unchanged (2.54 N.m/kg) (below the control value - 3.06 N.m/kg), and at the six-month follow-up, increased by approximately 20% (3.08 N.m/kg). For the hamstrings, at 60 °/s, an increase of 18 % occurred after intervention (1.98 N.m/kg) and by approximately 30 % at the six-month follow-up (2.12 N.m/kg) - values much higher than the control 1.55 N.m/kg). This increase in the PT/BM was also reflected in the Hamstrings:Quadriceps ratio (78 %) after treatment which improved at follow-up (68 %). The results showed that the isokinetic training and neuromuscular/proprioceptive exercises improved the muscle performance of the knee flexors and extensors, after eleven weeks of intervention, and remained (or continued to improve) at the six-month follow-up. 5, single case report.


Hypertension and psychosis.
Hypertension, a prevalent component of metabolic syndrome (MetS), is a well-known risk factor for cardiovascular diseases (CVD). Psychosis is a feature in the schizophrenia spectrum. Meta-analysis suggests that the prevalence of hypertension in schizophrenia and related disorders is 39%. This may be explained by a unidirectional association between hypertension and psychosis, in that psychosis can be a causative factor of hypertension via antipsychotic medication, inflammation and irregular autonomic nervous system activity through multiple mechanisms. Obesity is a side effect of antipsychotic medication and is a risk factor for hypertension. Obesity leads to raised blood pressure, atherosclerosis, increased triglyceride concentration and decreased high-density lipoprotein concentration. Inflammation accompanies hypertension and obesity. In recent years, the role of inflammation in the onset of psychosis has been increasingly recognised. It underlies the immune dysregulation observed in both schizophrenia and bipolar disorder. Interleukin-6, a marker and driver of inflammation, is related to obesity and plays a role in the pathogenesis of MetS and hypertension. The lack of preventive care of hypertension and other MetS risk factors for patients on antipsychotic medication is reflected in the high incidence of CVD in this population. It is important to detect and treat MetS and hypertension in patients with psychosis in order to reduce cardiovascular morbidity and mortality in this population.


[Healing of abdominal skin wounds in rats].
The studies performed on rats have shown that healing of square full-tissue skin wounds depends on their location. Thus, the healing of wounds on the belly was faster and more complete than that of dorsally located ones. Regeneration of belly skin resulted in the formation of new tissue with a typical network of fibers and skin folds. On the back epithelial connective tissue scars were formed.


[Network of integrated services : regulation and driving force of implementation of change.].
Networks of integrated services are often presented as a major path of solution to increase efficiency, relevance and coherence of health systems especially in the current context of increasing demand and budgetary restraint. In the mental health field, integation also attempts to answer the numerous needs of a targeted population and more specifically, people with serious mental disorders. This article describes the markers of the concept of network of integrated services in mental health, the major strategies favoring development and models of regulation allowing their elaboration. The article discusses difficulties and stakes of this mode of organization and more particularly the challenges linked to implementation of change and transformation of systems.


Measles resurgence in Argentina: 1997-8 outbreak.
Epidemiological and clinical findings from 1162 serologically confirmed measles cases occurring in Buenos Aires, Argentina in 1997 and 1998 were retrospectively reviewed. From 90 hospitalized children, measles virus was detected by direct RT-PCR from nasopharyngeal secretions. Patients were grouped as follows: (i) not vaccinated: infants < 12 months; (ii) regularly vaccinated: children 1-4 years not covered by the last catch-up; (iii) catch-up vaccinated: patients 5-19 years immunized during the 1993 campaign. Most cases were recorded in non-vaccinated infants (54%), and the lowest in catch-up vaccinated children (16%). Mean age of the 90 hospitalized children was 11.3 months. Pneumonia was the major hospitalization cause followed by pneumonitis. Two children required intensive care and one died. The 1993 catch-up campaign seemed to reduce the number of cases in the 5- to 19-year-old group. Lack of timely follow-up probably led to the accumulation of susceptible individuals allowing measles re-emergence. Direct viral detection by RT-PCR proved to be a sensitive tool for molecular epidemiology surveillance.


Omenn syndrome: a rare case of neonatal erythroderma.
Omenn syndrome is a severe combined immunodeficiency characterized by erythroderma, hepatosplenomegaly, lymphadenopathy and failure to thrive, with activated oligoclonal T lymphocytes and an absence of circulating B cells.A 3 day-old boy presented with a congenital erythroderma. Investigations revealed a marked neutropenia and lymphopenia and the absence of a thymus. Genetic studies showed RAG 1 mutations. He was successfully treated with an HLA identical bone marrow transplantation. Omenn syndrome is a rare severe combined immunodeficiency. Most cases are due to mutations in the RAG genes with autosomal recessive transmission. Our observation is original because of an incomplete clinical presentation. During the course of the disease, the child had no failure to thrive, no organomegaly and no recurrent infection. Immunodeficiency must be excluded in every case of neonatal erythroderma and an immunological assessment should be performed without delay.


[Patent ductus arteriosus and pulmonary artery endarteritis].
We describe a seven year old girl with echocardiographic diagnosis of pulmonary artery endarteritis as a complication of a patent ductus arteriosus, confirmed at surgery. This case illustrates the necessity of complete surgical resection of the infectious source as a way to avoid other complications such as pulmonary embolism.


Theoretical and Experimental Investigation of the Translational Diffusion of Proteins in the Vicinity of Temperature-Induced Unfolding Transition.
Translational diffusion is the most fundamental form of transport in chemical and biological systems. The diffusion coefficient is highly sensitive to changes in the size of the diffusing species; hence, it provides important information on the variety of macromolecular processes, such as self-assembly or folding-unfolding. Here, we investigate the behavior of the diffusion coefficient of a macromolecule in the vicinity of heat-induced transition from folded to unfolded state. We derive the equation that describes the diffusion coefficient of the macromolecule in the vicinity of the transition and use it to fit the experimental data from pulsed-field-gradient nuclear magnetic resonance (PFG NMR) experiments acquired for two globular proteins, lysozyme and RNase A, undergoing temperature-induced unfolding. A very good qualitative agreement between the theoretically derived diffusion coefficient and experimental data is observed.


Cardiac effects of amiloride and of enalapril in the spontaneously hypertensive rat.
To compare the effects of the sodium-hydrogen exchange blocker, amiloride, with those of the angiotensin-converting enzyme inhibitor, enalapril, on cardiac structure and function and intracardiomyocyte calcium concentration ([Ca2+]i) and pH (pHi), in spontaneously hypertensive rats (SHRs). Experiments were performed in SHRs treated for 4 weeks with amiloride 7.5 mg/kg per day, enalapril 6.0 mg/kg per day or vehicle, and in Sprague-Dawley rats (SDRs). After haemodynamic measurements were taken, the heart was removed and weighed and hydroxyproline (a marker of collagen content) was assayed. In separate rats, ventricular myocytes were isolated, their size determined, and [Ca2+]i and pHi examined using fluo-3 acetoxymethyl ester and 2',7'-bis(2-carboxyethyl)-5(6)-carboxyfluorescein tetrakis acetoxymethyl ester fluorescence, respectively. Left ventricular end-diastolic pressure was increased, and the maximal rates of increase and of decrease in pressure with time in the left ventricle were decreased in SHRs compared with SDRs. Myocytes were larger and hydroxyproline was increased in the left ventricle, but not in the right ventricle of SHRs compared with SDRs. Amiloride and enalapril decreased systolic blood pressure in SHRs similarly, and improved diastolic function in these rats, enalapril more than amiloride. Both agents decreased left ventricular myocyte size to similar extents; however, whereas enalapril decreased the left ventricular hydroxyproline content, amiloride did not. Left ventricular myocytes from SHRs exhibited greater [Ca2+]i and pHi than those from SDRs; enalapril decreased [Ca2+]i more than amiloride, but amiloride decreased pHi more than enalapril. In SHRs, enalapril prevents left ventricular hypertrophy, collagen deposition, diastolic dysfunction, and increases in [Ca2+]i more effectively than does amiloride. In contrast, the latter prevents the increase in pHi more effectively than enalapril, despite similar reductions in blood pressure. These findings suggest that their effects do not depend solely on blood pressure reduction.


What are we missing in the clinical trials of focal segmental glomerulosclerosis?
Focal segmental glomerulosclerosis (FSGS) is a lesion and not a disease. This conundrum is the crux of controversies regarding interventions to alter its natural history. In the broadest sense, the lesion can be primary (idiopathic), or secondary to a process originating outside the kidneys or to a genetic mutation. The organ-based target is the podocyte, and the mechanisms responsible for the podocytopathy are numerous and diverse. Recurrence of primary FSGS in renal allografts provides the best evidence for the existence of a circulating factor or factors, the nature of which remains uncertain. The separation of primary from secondary FSGS clinically and pathologically is challenging, but full-blown nephrotic syndrome and diffuse (universal) foot process effacement are strong signals for a primary form of FSGS. It is imperative that clinical trials designed to investigate therapeutic strategies for patients with a lesion of FSGS pay careful attention to the separation of primary from secondary forms of FSGS. This critical review provides a rationale and a process for helping to ensure that this is accomplished, such that clinical trials provide useful information and treatment responsiveness applicable to the primary forms of FSGS.


Tropospheric Emissions: Monitoring of Pollution (TEMPO).
TEMPO was selected in 2012 by NASA as the first Earth Venture Instrument, for launch between 2018 and 2021. It will measure atmospheric pollution for greater North America from space using ultraviolet and visible spectroscopy. TEMPO observes from Mexico City, Cuba, and the Bahamas to the Canadian oil sands, and from the Atlantic to the Pacific, hourly and at high spatial resolution (~2.1 km N/S×4.4 km E/W at 36.5°N, 100°W). TEMPO provides a tropospheric measurement suite that includes the key elements of tropospheric air pollution chemistry, as well as contributing to carbon cycle knowledge. Measurements are made hourly from geostationary (GEO) orbit, to capture the high variability present in the diurnal cycle of emissions and chemistry that are unobservable from current low-Earth orbit (LEO) satellites that measure once per day. The small product spatial footprint resolves pollution sources at sub-urban scale. Together, this temporal and spatial resolution improves emission inventories, monitors population exposure, and enables effective emission-control strategies. TEMPO takes advantage of a commercial GEO host spacecraft to provide a modest cost mission that measures the spectra required to retrieve ozone (O3), nitrogen dioxide (NO2), sulfur dioxide (SO2), formaldehyde (H2CO), glyoxal (C2H2O2), bromine monoxide (BrO), IO (iodine monoxide),water vapor, aerosols, cloud parameters, ultraviolet radiation, and foliage properties. TEMPO thus measures the major elements, directly or by proxy, in the tropospheric O3 chemistry cycle. Multi-spectral observations provide sensitivity to O3 in the lowermost troposphere, substantially reducing uncertainty in air quality predictions. TEMPO quantifies and tracks the evolution of aerosol loading. It provides these near-real-time air quality products that will be made publicly available. TEMPO will launch at a prime time to be the North American component of the global geostationary constellation of pollution monitoring together with the European Sentinel-4 (S4) and Korean Geostationary Environment Monitoring Spectrometer (GEMS) instruments.


Human parainfluenza virus type 3 (PIV3) expressing the hemagglutinin protein of measles virus provides a potential method for immunization against measles virus and PIV3 in early infancy.
Recombinant human parainfluenza virus type 3 (PIV3) was used as a vector to express the major protective antigen of measles virus, the hemagglutinin (HA) glycoprotein, in order to create a bivalent PIV3-measles virus that can be administered intranasally. The measles virus HA open reading frame (ORF) was inserted as an additional transcriptional unit into the N-P, P-M, or HA-neuraminidase (HN)-L gene junction of wild-type PIV3 or into the N-P or P-M gene junction of an attenuated derivative of PIV3, termed rcp45L. The recombinant PIV3 (rPIV3) viruses bearing the HA inserts replicated more slowly in vitro than their parental viruses but reached comparable peak titers of >/=10(7.5) 50% tissue culture infective doses per ml. Each of the wild-type or cold-passaged 45L (cp45L) PIV3(HA) chimeric viruses replicated 5- to 10-fold less well than its respective parent virus in the upper respiratory tract of hamsters. Thus, insertion of the approximately 2-kb ORF itself conferred attenuation, and this attenuation was additive to that conferred by the cp45L mutations. The attenuated cp45L PIV3(HA) recombinants induced a high level of resistance to replication of PIV3 challenge virus in hamsters and induced very high levels of measles virus neutralizing antibodies (>1:8,000) that are well in excess of those known to be protective in humans. rPIV3s expressing the HA gene in the N-P or P-M junction induced about 400-fold more measles virus-neutralizing antibody than did the rPIV3 with the HA gene in the HN-L junction, indicating that the N-P or P-M junction appears to be the preferred insertion site. Previous studies indicated that the PIV3 cp45 virus, a more attenuated version of rcp45L, replicates efficiently in the respiratory tract of monkeys and is immunogenic and protective even when administered in the presence of very high titers of passively transferred PIV3 antibodies (A. P. Durbin, C. J. Cho, W. R. Elkins, L. S. Wyatt, B. Moss, and B. R. Murphy, J. Infect. Dis. 179:1345-1351, 1999). This suggests that this intranasally administered PIV3(HA) chimeric virus can be used to immunize infants with maternally acquired measles virus antibodies in whom the current parenterally administered live measles virus vaccine is ineffective.


[The son of man. Freud's Oedipus myth].
In formulating his psychology of the unconscious, Freud makes constant reference to Sophocles' version of the Oedipus myth. The author provides detailed proof of the fundamental differences between the two versions, demonstrating that Freud's interpretation does violence to the source. Bollack marshals impressive evidence to substantiate his contention that from the early letters to Fliess all the way up to Moses and Monotheism Freud's sole concern was to point up the ubiquitous power of the unconscious (incestual desire, patricide) within the "holy" (nuclear) family, whereas Sophocles was preoccupied with an entirely different problem. In Bollack's view, Oedipus rex is the drama of the self-destruction of a royal family, a drama in which incest and murder have no very essential significance. Freud, by contrast, set out to de-mystify the fate that dogs the royal family from one generation to the next and to naturalise it into a form of unconscious behaviour--a tendency which Bollack sees as deriving from the tradition of the "drama of destiny", a genre prevalent in the 19th century.


Autophagy-associated proteins BAG3 and p62 in testicular cancer.
Testicular germ cell tumors (TGCT) represent the most common malignant tumor group in the age group of 20 to 40-years old men. The potentially curable effect of cytotoxic therapy in TGCT is mediated mainly by the induction of apoptosis. Autophagy has been discussed as an alternative mechanism of cell death but also of treatment resistance in various types of tumors. However, in TGCT the expression and role of core autophagy-associated factors is hitherto unknown. We designed the study in order to evaluate the potential role of autophagy-associated factors in the development and progression of testicular cancers. Eighty-four patients were assessed for autophagy (BAG3, p62) and apoptosis (cleaved caspase 3) markers using immunohistochemistry (IHC) on tissue micro- arrays. In addition, western blot analyses of frozen tissue of seminoma and non-seminoma were performed. Our findings show that BAG3 was significantly upregulated in seminoma as compared to non-seminoma but not to normal testicular tissue. No significant difference of p62 expression was detected between neoplastic and normal tissue or between seminoma and non-seminoma. BAG3 and p62 showed distinct loco‑regional expression patterns in normal and neoplastic human testicular tissues. In contrast to the autophagic markers, apoptosis rate was significantly higher in testicular tumors as compared to normal testicular tissue, but not between different TGCT subtypes. The present study, for the first time, examined the expression of central autophagy proteins BAG3 and p62 in testicular cancer. Our findings imply that in general apoptosis but not autophagy induction differs between normal and neoplastic testis tissue.


[Application progress of on-line sample preparation techniques coupled with liquid chromatography-mass spectrometry system in the detection of food hazards].
Food safety has received increased attention, and food detection is of great significance. The food matrix is complex, and diverse food hazards have been identified. Thus, the detection methods and sample preparation techniques for food matrices must be continuously optimized and updated. Several steps are usually required when a chromatographic system is used to determine food hazards: sample preparation, that is, the separation of targets from different substrates using a suitable preprocessing method and target-substance separation and purification, which is usually achieved using chromatographic separation. The selection of an appropriate detector for qualitative and quantitative analyses is usually based on the properties of the target compound. The sample preparation procedure is considered the most time-consuming aspect of the entire food-analysis process. It is also prone to analytical errors. Therefore, optimization of the sample preparation process is a key issue in the field of chemical analysis. Researchers have developed a series of new, efficient, and accurate sample preprocessing methods, and an on-line sample-preparation system has been found to be a feasible approach. On-line sample preparation coupled with liquid chromatography-mass spectrometry (LC-MS) presents many advantages. First, manual operation could reduce analytical errors to ensure good accuracy and repeatability. It could also reduce the consumption of chemical reagents and avoid cross-contamination between samples. Furthermore, an on-line sample-preparation system could shorten the sample-preparation time and improve the detection efficiency. On-line sample preparation coupled with LC-MS has been widely applied in the fields of environment, biology, and food. On-line sample preparation systems coupled with LC-MS are divided into two modules: the first modules involves sample preparation and the second module involves the LC system. The first module remove impurities and isolates the target compounds in preparation for their qualitative and quantitative detection. The coupling of these two modules depends mainly on valve switching. In this paper, we introduce the most frequently used on-line sample-preparation techniques, including on-line solid phase extraction (on-line SPE), in-tube solid phase microextraction (in-tube SPME), and turbulent chromatography (TFC). We then describe the basic principles and coupling equipment of these three on-line analytical technologies in detail. The coupling equipment establishes a physical connection between the two modules. Next, we discuss the properties of different purification fillers in an on-line sample-preparation column. The applications and research progress of on-line systems for pesticide residues, veterinary drug residues, and biotoxins are also discussed. Compared with offline sample preparation, on-line analytical systems present several advantages. On-line analytical systems can not only greatly reduce the analysis time and solvent consumption but also improve the detection sensitivity and accuracy. Such systems can be used to determine food hazards to ensure food safety. Finally, the existing problems and development trends of on-line analytical systems are discussed and prospected. To promote the applications of on-line analytical technology in food-safety detection, we suggest that the following three aspects be considered. First, more on-line purification columns with novel fillers, in addition to C18 or polymer fillers, should be developed. Second, compared with ordinary detectors, high-resolution MS detectors have better precision and accuracy. Coupling on-line analytical technologies with a high-resolution mass spectrometer may be beneficial for the further development of on-line analyses. Third, different food matrices should be compared and evaluated to continuously optimize the detection process and improve the efficiency of on-line analytical systems. As concerns regarding food safety issues have increased, the applications of on-line analytical technologies for food detection can be expected to become increasingly important.


Baseline characteristics and Latino versus non-Latino contrasts among Bronx A1C study participants.
We describe baseline demographic and psychosocial characteristics of low-income, diverse diabetes adults enrolled in a telephonic intervention trial. Environment for the study was New York City (NYC) A1C Registry program. Baseline data were analyzed from 941 participants randomized to either telephonic/print or print-only intervention to improve glycemic control. Summary statistics for key variables were calculated; we highlight baseline contrasts between Latino and non-Latino participants. There were high proportions of Latino (67.7%) and non-Latino Black (28.0%) participants from South Bronx. Mean age was 56.3 years, almost 70.0% were foreign born, and 55.8% preferred Spanish language. Mean A1C was 9.2% and mean body mass index (BMI) 32.1 kg/m(2). There were significant contrasts between Latino and non-Latino participants for behavioral and psychosocial variables. This telephonic intervention study succeeded in randomizing a large number of low-income, diverse participants with poor diabetes control who are under-represented in studies. Latino versus non-Latino differences at baseline were striking.


[Arterial hypertension: current principles of therapy].
The paper outlines basic pathogenetic mechanisms of arterial hypertension (AH) including endothelial dysfunction, influence of risk factors and associated clinical conditions on AH prognosis; presents conception of AH risk stratification, aim and policy of antihypertensive drugs administration depending on the risk degree, the treatment algorithm; considers the problem of inadequate control of arterial pressure; provides criteria of assessing effectiveness of antihypertensive therapy.


Refining the pole-and-collar method of restraint: emphasizing the use of positive training techniques with rhesus macaques (Macaca mulatta).
The pole-and-collar method is one of several techniques that enable the safe transfer of a nonhuman primate from its home environment into a restraint chair without the need for sedation. It has been used within the scientific community for decades. Traditional methods to train animals for pole-and-collar use rely primarily on aspects of negative reinforcement, with very little incorporation of positive-reinforcement techniques. With increasing emphasis on animal training and welfare, research facilities are incorporating positive-reinforcement training into husbandry and experimental procedures. Here we demonstrate the feasibility of training rhesus macaques (Macaca mulatta; n = 8) to cooperate for pole-and-collar transfer to a primate restraint chair. By using predominantly positive-reinforcement techniques, with supplemental elements of negative reinforcement, macaques were trained in a mean of 85 training sessions (a mean of 1085 min of training time). We also provide tools for investigators using the pole-and-collar method to help them successfully incorporate positive-reinforcement training into their procedures. This refinement has the potential to improve animal welfare and enhance the value of nonhuman primate models in research.


Cross-tolerance to metkephamid (LY127623) produced by morphine solution ingestion by mice.
The effects of morphine and metkephamid were determined on the writhing test in drug-naive mice and mice that had been exposed to morphine solutions as their sole fluid source for a 5- or 7-day period. The average dose of morphine consumed was 435 mg/kg, using either 0.5 mg/ml solution for 7 days or a 1 mg/ml solution for 5 days. The ingestion of these morphine solutions produced a marked tolerance to the analgesic effects of morphine and cross-tolerance to the analgesic effects of metkephamid.


[Specifics of Hodgkin's disease in children younger than 10 years].
The study group of patients under 10 years of age formed on the basis of certain clinico-epidemiological criteria proved to differ in some respects substantially from those under 15 years, including the end-results. The latter findings cannot be accounted for by insignificant differences in prognostic factor frequency alone. It is suggested that the significantly worse end-results recorded for the older patients be attributed to factors like pubescence and age-related changes in the body.


An attenuated philosophical gentleman.
Dr. Joseph Black had at one time, a house near us to the west. He was a striking and beautiful person; tall, very thin, and cadaverously pale; his hair carefully powdered, though there was little of it except what was collected in a long thin queue; his eyes dark, clear and large, like deep pools of pure water. He wore black speckless clothes, silk stockings, silver buckles, and either a slim green umbrella, or a genteel brown cane. The general frame and air were feeble and slender. The wildest boy respected Black. No lad could be irreverent toward a man so pale, so gentle, so elegant and so illustrious. So he glided, like a spirit, through our rather mischievous sportiveness, unharmed. He died seated, with a bowl of milk upon his knee, of which his ceasing to be did not spill a drop; a departure which it seemed, after the event, might have been foretold of this attenuated philosophical gentleman.


Prevention and management of allergic reactions to food in child care centers and schools: Practice guidelines.
Food allergy management in child care centers and schools is a controversial topic, for which evidence-based guidance is needed. Following the Grading of Recommendations Assessment, Development, and Evaluation approach, we conducted systematic literature reviews of the anticipated health effects of selected interventions for managing food allergy in child care centers and schools; we compiled data about the costs, feasibility, acceptability, and effects on health equity of the selected interventions; and we developed the following conditional recommendations: we suggest that child care centers and schools implement allergy training and action plans; we suggest that they use epinephrine (adrenaline) to treat suspected anaphylaxis; we suggest that they stock unassigned epinephrine autoinjectors, instead of requiring students to supply their own personal autoinjectors to be stored on site for designated at-school use; and we suggest that they do not implement site-wide food prohibitions (eg, "nut-free" schools) or allergen-restricted zones (eg, "milk-free" tables), except in the special circumstances identified in this document. The recommendations are labeled "conditional" due to the low quality of available evidence. More research is needed to determine with greater certainty which interventions are likely to be the most beneficial. Policymakers might need to adapt the recommendations to fit local circumstances.


Neuronal Loss of the Glutamate Transporter GLT-1 Promotes Excitotoxic Injury in the Hippocampus.
GLT-1, the major glutamate transporter in the mammalian central nervous system, is expressed in presynaptic terminals that use glutamate as a neurotransmitter, in addition to astrocytes. It is widely assumed that glutamate homeostasis is regulated primarily by glutamate transporters expressed in astrocytes, leaving the function of GLT-1 in neurons relatively unexplored. We generated conditional GLT-1 knockout (KO) mouse lines to understand the cell-specific functions of GLT-1. We found that stimulus-evoked field extracellular postsynaptic potentials (fEPSPs) recorded in the CA1 region of the hippocampus were normal in the astrocytic GLT-1 KO but were reduced and often absent in the neuronal GLT-1 KO at 40 weeks. The failure of fEPSP generation in the neuronal GLT-1 KO was also observed in slices from 20 weeks old mice but not consistently from 10 weeks old mice. Using an extracellular FRET-based glutamate sensor, we found no difference in stimulus-evoked glutamate accumulation in the neuronal GLT-1 KO, suggesting a postsynaptic cause of the transmission failure. We hypothesized that excitotoxicity underlies the failure of functional recovery of slices from the neuronal GLT-1 KO. Consistent with this hypothesis, the non-competitive NMDA receptor antagonist MK801, when present in the ACSF during the recovery period following cutting of slices, promoted full restoration of fEPSP generation. The inclusion of an enzymatic glutamate scavenging system in the ACSF conferred partial protection. Excitotoxicity might be due to excess release or accumulation of excitatory amino acids, or to metabolic perturbation resulting in increased vulnerability to NMDA receptor activation. Previous studies have demonstrated a defect in the utilization of glutamate by synaptic mitochondria and aspartate production in the synGLT-1 KO in vivo, and we found evidence for similar metabolic perturbations in the slice preparation. In addition, mitochondrial cristae density was higher in synaptic mitochondria in the CA1 region in 20-25 weeks old synGLT-1 KO mice in the CA1 region, suggesting compensation for loss of axon terminal GLT-1 by increased mitochondrial efficiency. These data suggest that GLT-1 expressed in presynaptic terminals serves an important role in the regulation of vulnerability to excitotoxicity, and this regulation may be related to the metabolic role of GLT-1 expressed in glutamatergic axon terminals.