Long-term outcome following placement of percutaneous endoscopic gastrostomy in younger and older patients.
Percutaneous endoscopic gastrostomy (PEG) is the method of choice in maintaining enteral nutrition in patients with swallowing and nutritional disorders of different etiology. The aim of this study was to assess the long-term outcome of patients following placement of a PEG. All patients who received a PEG between October 1999 and September 2000 were included in this prospective study. Long-term function, replacement or removal of the PEG, complications and survival of the patients were analyzed in group A (younger than 75 years) and group B (75 years or older). The indications for PEG placement in group A (54 patients, mean age 54.5 years) were neurological (66.7%) and malignant (31.5%) disorders, whereas in group B (40 patients, mean age 81 years) the indications were predominantly neurological diseases (87.5%). The majority of patients (91 of 94 patients; 96.8%) could be followed long term or until death. In group A, 46 patients (85.2%) had uncomplicated long-term function of their PEG and interventions were necessary in only 8 patients. Removal of the PEG was possible during the course in 17 patients (31.5%). In group B, uncomplicated long-term function was observed in 34 patients (85%) and interventions were required in only 6 patients. Removal of the PEG was not possible in group B. Survival rates for 1-, 2- and 5 years in group A were 73.9%, 61.8% and 43.9%, respectively, and in group B 41.4%, 31.9% and 15.9%, respectively; the difference was statistically significant (p=0.002). Excellent long-term function of PEG was seen in this study of 94 consecutive patients, and interventions were necessary only in a minority of patients. The prognosis for older patients was worse; however, the 2-year survival rate of 32% justified the PEG insertion.


[Acute interstitial nephritis associated to lamotrigine use. Report of one case].
Acute interstitial nephritis is a mononuclear and sterile inflammation of the renal interstice caused by drugs, infections or immune phenomena. The clinical presentation is characterized by the triad of rash, fever and eosinophilia. We report a 32 years old man, in treatment with lamotrigine for depression, admitted to the hospital due to fever, abdominal pain, jaundice, cutaneus rash and malaise. Due to an oliguric renal failure of acute onset, a renal biopsy was done. The pathological study showed a granulomatous acute interstitial nephritis. He was started on hemodialysis and treated with cessation of the drug and corticosteroids, with complete recovery of the renal function.


Sub-patterns of language network reorganization in pediatric localization related epilepsy: a multisite study.
To study the neural networks reorganization in pediatric epilepsy, a consortium of imaging centers was established to collect functional imaging data. Common paradigms and similar acquisition parameters were used. We studied 122 children (64 control and 58 LRE patients) across five sites using EPI BOLD fMRI and an auditory description decision task. After normalization to the MNI atlas, activation maps generated by FSL were separated into three sub-groups using a distance method in the principal component analysis (PCA)-based decisional space. Three activation patterns were identified: (1) the typical distributed network expected for task in left inferior frontal gyrus (Broca's) and along left superior temporal gyrus (Wernicke's) (60 controls, 35 patients); (2) a variant left dominant pattern with greater activation in IFG, mesial left frontal lobe, and right cerebellum (three controls, 15 patients); and (3) activation in the right counterparts of the first pattern in Broca's area (one control, eight patients). Patients were over represented in Groups 2 and 3 (P < 0.0004). There were no scanner (P = 0.4) or site effects (P = 0.6). Our data-driven method for fMRI activation pattern separation is independent of a priori notions and bias inherent in region of interest and visual analyses. In addition to the anticipated atypical right dominant activation pattern, a sub-pattern was identified that involved intensity and extent differences of activation within the distributed left hemisphere language processing network. These findings suggest a different, perhaps less efficient, cognitive strategy for LRE group to perform the task.


Pain catastrophizing is associated with dental pain in a stressful context.
Pain is associated with anxiety in a dental setting. It has remained unclear how cognitive-affective factors modulate pain and anxiety in a stressful context, such as receiving dental procedures. We hypothesized that both the situational factor (unpredictability about painful stimuli) and the trait factor (pain catastrophizing, i.e., the tendency to interpret pain in negative orientation) account for dental pain. Fifteen healthy participants were recruited to perform an associative learning task. They were asked to learn the pairing between visual cues and the intensity of incoming painful stimuli delivered at the right upper central incisor. Brain activation associated with pain was recorded by functional magnetic resonance imaging (fMRI). The participants reported increased anxiety and pain in the stressful context, where stimuli intensity was not predicted by the preceding cue. The score of the Pain Catastrophizing Scale was positively correlated with the increased pain modulated by unpredictability. Brain activation at the right posterior hippocampus, a region critically related to associative learning of aversive stimuli and context, was correlated with the individual catastrophizing level. Our findings suggest that both the situational factor (unpredictability) and the trait factor (catastrophizing) influence dental pain, highlighting the role of cognitive-affective factors in pain control of dental patients.


Observed noncompliance with implementation of vector-borne disease preventive measures among deployed forces.
Failure by individual service members and units to implement preventive measures to mitigate environmental health threats have always resulted in reduced efficiency of the Warfighter, with the attendant reduction in combat capability. This article describes observations at 2 sites in northern Iraq from July 2007 to September 2009 of deficiencies in the use of preventive and protective measures to reduce incidences of vector-borne diseases. Observations included individual service member s indifference or negative attitude toward use of personal protective equipment and unit leaders failure to provide required resources and enforce use of personal protective measures. Implications of these actions and recommendation for enhancing compliance are discussed.


Effects of tofacitinib in early arthritis-induced bone loss in an adjuvant-induced arthritis rat model.
The main goal of this work was to analyse how treatment intervention with tofacitinib prevents the early disturbances of bone structure and mechanics in the rat model of adjuvant-induced arthritis. This is the first study to access the impact of tofacitinib on the skeletal bone effects of inflammation. Fifty Wistar rats with adjuvant-induced arthritis were randomly housed in experimental groups, as follows: non-arthritic healthy group (n = 20); arthritic non-treated group (n = 20); and 10 animals undergoing tofacitinib treatment. Rats were monitored during 22 days after disease induction for the inflammatory score, ankle perimeter and body weight. Healthy non-arthritic rats were used as controls for comparison. After 22 days of disease progression, rats were killed and bone samples collected for histology, micro-CT, three-point bending and nanoindentation analysis. Blood samples were also collected for quantification of bone turnover markers and systemic cytokines. At the tissue level, measured by nanoindentation, tofacitinib increased bone cortical and trabecular hardness. However, micro-CT and three-point bending tests revealed that tofacitinib did not reverse the effects of arthritis on the cortical and trabecular bone structure and on mechanical properties. Possible reasons for these observations might be related to the mechanism of action of tofacitinib, which leads to direct interactions with bone metabolism, and/or to the kinetics of its bone effects, which might need longer exposure.


Evidence for two koi herpesvirus (KHV) genotypes in South Korea.
The geographic distribution of koi herpesvirus (KHV) has recently been analyzed by polymerase chain reaction (PCR, based on the alleles of 3 domains) and sequence analysis using 3 regions of KHV genomic DNA (SphI-5, 9/5, and the thymidine kinase gene). In this study, samples from 6 carp showing symptoms of KHV infection in 2008 were examined for the presence of KHV by using PCR and cell culture isolation methods. KHV was detected in 2 (Pyeongtaek and Buan) of the samples. Sequence analysis revealed that the genotype of the KHV PT-08 isolate was Asia genotype variant 1 (A1), and the genotype of the KHV BA-08 isolate was European genotype variant 4 (E4). In addition, PCR patterns and sequence analysis based on the alleles of 3 domains of an alternate KHV classification system confirmed that the genotype of the KHV PT-08 isolate was CyHV3-J, and the genotype of the KHV BA-08 isolate was CyHV3-third genotype. To our knowledge, this is the first study to demonstrate the presence of 2 genotypes of KHV (genotype A1/CyHV3-J; genotype E4/CyHV3-third genotype) in South Korea.


Longitudinal analysis of motor symptoms and histopathology in woozy mice, a model of cerebellar ataxia.
Woozy (wz) mice develop ataxia and carry a mutation in the Sil1 gene. Homozygous wz mice have been characterized histopathologically, but no details of their motor function have been reported. In the present study, to comprehensively understand the relationship between symptomatic progression and pathological feature, we evaluated motor function and neurodegeneration with age from presymptomatic to terminal stages. We evaluated the motor function of homozygous and heterozygous wz mice aged from 5 to 71 weeks. Motor function was evaluated using the rotarod test, the footprint test, and the parallel rod floor test. Furthermore, we carried out a histopathological analysis of the mice at several ages. Impairment of motor function in homozygous wz mice began at around 11 weeks of age and became markedly worse until around 14 weeks. Heterozygous wz mice did not show motor dysfunction until 71 weeks of age. Features of cerebellar ataxia were evaluated using the footprint test and the parallel rod floor test. In addition to the observation of ubiquitin-positive aggregates at 6 weeks of age, Purkinje cell loss at 9 weeks of age and cerebellar atrophy were confirmed by histopathology. Apart from the cerebellar changes, we detected no other pathology that could contribute toward ataxia. In heterozygous wz mice, only minimal formation of ubiquitin-positive aggregates was observed. Homozygous wz mice showed adult-onset ataxia with progressive neurodegeneration of the cerebellum. Homozygous wz mice might be useful as an animal model of diseases showing adult-onset ataxia because of cerebellar neurodegeneration.


[Myoglobin and mitochondria: kinetics of oxymyoglobin deoxygenation in mitochondria suspension].
The kinetics of whale MbO2 deoxygenation was studied spectrophotometrically in the presence of breathing rat mitochondria under conditions when mitochondria were separated from the protein solution by a semipermeable film capable to transfer only low-molecular-weight compounds and directly in the solution of MbO2 with mitochondria (incubation medium: 15-35 mM succinate, 150 mM sucrose, 100 mM KCl, 0.5 mM EGTA, 5 mM KH2PO4, 10 mM MOPS, pH 7.4). It was shown that the splitting of O2 from MbO2 at physiological pO2 is possible only if it directly contacts mitohondria. The deoxygenation rate does not depend on the protein concentration (zero order on [MbO2] as opposite to the first order reaction in the absence of mitochondria) and completely coincides with the rate of oxygen consumption by mitochondria under the same conditions, as indicated by the polarographic data. The dependence of the MbO2 deoxygenation rate on the concentration of mitochondria and the protein, and on the total charge of the MbO2 molecule was studied using horse MbO2 (pI 7.1), sperm whale MbO2 (pI 8.3), its zinc complex, Zn-MbO2 (pI > 8.3), and the sperm whale MbO2 derivative carboxymethylated at His residues, CM-MbO2 (pI 5.2). The mechanism of MbO2 deoxygenation in the cell obviously actuates its interplay with the mitochondrial membrane. As a result, the affinity of Mb to oxygen decreases several times, which corresponds to a shift of the Mb dissociation curve to higher pO2 values.


Modeling biogeochemical dynamics in porous media: Practical considerations of pore scale variability, reaction networks, and microbial population dynamics in a sandy aquifer.
Prediction of the fate and environmental impacts of groundwater contaminants requires the identification of relevant biogeochemical processes and necessitates the macroscopic representation of microbial activity occurring at the microscale. Using a well-studied sandy aquifer environment, we evaluate the importance of pore distribution on organic matter respiration in a porous medium environment by performing spatially explicit simulations of microbial metabolism at the sub-millimeter scale. Model results using an idealized porous medium under non-biofilm forming conditions indicate that while some heterogeneity is observed for flow rates, distributions of microbes and dissolved organic substrates remain relatively homogenous at the grain scale. At the macroscale in the same environment, we assess the impact of a comprehensive reaction network description for a phenolic contaminant plume, and compare the findings to a setting describing organic matter breakdown in a coastal marine sediment. This comparison reveals the importance of reactions recycling reduced metabolites at redox interfaces, leading to a competition for oxidants. When the spatio-temporal dynamics of microbial groups are accounted for, our simulations show the importance of reaction energetics and nutrient limitations such as microbial nitrogen demands.


[Surveillance of the lab personnel exposed to HIV and other bloodborne viruses].
The results of 15 years of surveillance of the laboratory personnel with different levels of exposure to HIV and other bloodborne viruses like HCV, HBV and HTLV-1 were presented. Various biosafety measures were applied and ELISA was used as the main lab technique. 628 serum samples were analyzed for HIV whereas 354 for the rest of the viruses but no lab-acquired infection was detected. This indicates the low incidence of HIV infection in health care workers at risk and the great importance of biosafety measures in the prevention and early detection of these infections.


Construction of Highly Stable Cytotoxic Nuclear-Directed Ribonucleases.
Ribonucleases are proteins whose use is promising in anticancer therapy. We have previously constructed different human pancreatic ribonuclease variants that are selectively cytotoxic for tumor cells by introducing a nuclear localization signal into their sequence. However, these modifications produced an important decrease in their stability compromising their behavior in vivo. Here, we show that we can significantly increase the thermal stability of these cytotoxic proteins by introducing additional disulfide bonds by site-directed mutagenesis. One of these variants increases its thermal stability by around 17 °C, without affecting its catalytic activity while maintaining the cytotoxic activity against tumor cells. We also show that the most stable variant is significantly more resistant to proteolysis when incubated with proteinase K or with human sera, suggesting that its half-live could be increased in vivo once administered.


Sucrose favors Pseudomonas aeruginosa pellicle production through the extracytoplasmic function sigma factor SigX.
Pseudomonas aeruginosa biofilm formation was increased by addition of sucrose to Luria-Bertani medium, whereas addition of NaCl to a final similar osmolarity and use of maltose instead of sucrose, were ineffective. In a previous study, we showed that the extracytoplasmic sigma factor SigX is activated in the presence of sucrose. The sucrose-mediated pellicle increase was abolished in a sigX mutant strain. Sucrose addition led to an increase in pel expression and cyclic-diguanylate (c-di-GMP) pool level production. Interestingly, these two phenotypes were strongly decreased in a sigX mutant. Since pel is not known as a SigX-target, we suspect SigX to be involved in the c-di-GMP production. We found that expression of the diguanylate cyclase PA4843 gene was increased in the presence of sucrose at least partly through SigX activity. Our study shows that sucrose itself rather than osmolarity favours the biofilm mode of P. aeruginosa through the activation of SigX.


Fractured coracoid process in acromioclavicular dislocations. Report of four cases and review of the literature.
Acromioclavicular (AC) dislocation with a concomitant coracoid process fracture occurs infrequently. This fracture should be suspected with all AC dislocations occurring in the first three decades of life. An axillary lateral radiograph or tomogram often is needed to detect the fracture. Surgical treatment can produce good results, but equally satisfactory function with minimal residual cosmetic deformity may be achieved by nonsurgical measures.


CaPOW! Using Problem Sets in a Capstone Course to Improve Fourth-Year Medical Students' Confidence in Self-Directed Learning.
Despite the importance of self-directed learning (SDL) in the field of medicine, individuals are rarely taught how to perform SDL or receive feedback on it. Trainee skill in SDL is limited by difficulties with self-assessment and goal setting. Ninety-two graduating fourth-year medical students from Duke University School of Medicine completed an individualized learning plan (ILP) for a transition-to-residency Capstone course in spring 2015 to help foster their skills in SDL. Students completed the ILP after receiving a personalized report from a designated faculty coach detailing strengths and weaknesses on specific topics (e.g., pulmonary medicine) and clinical skills (e.g., generating a differential diagnosis). These were determined by their performance on 12 Capstone Problem Sets of the Week (CaPOWs) compared with their peers. Students used transitional-year milestones to self-assess their confidence in SDL. SDL was successfully implemented in a Capstone course through the development of required clinically oriented problem sets. Coaches provided guided feedback on students' performance to help them identify knowledge deficits. Students' self-assessment of their confidence in SDL increased following course completion. However, students often chose Capstone didactic sessions according to factors other than their CaPOW performance, including perceived relevance to planned specialty and session timing. Future Capstone curriculum changes may further enhance SDL skills of graduating students. Students will receive increased formative feedback on their CaPOW performance and be incentivized to attend sessions in areas of personal weakness.


TMAVA, a Metabolite of Intestinal Microbes, Is Increased in Plasma From Patients With Liver Steatosis, Inhibits γ-Butyrobetaine Hydroxylase, and Exacerbates Fatty Liver in Mice.
Nonalcoholic fatty liver disease is characterized by excessive hepatic accumulation of triglycerides. We aimed to identify metabolites that differ in plasma of patients with liver steatosis vs healthy individuals (controls) and investigate the mechanisms by which these might contribute to fatty liver in mice. We obtained blood samples from 15 patients with liver steatosis and 15 controls from a single center in China (discovery cohort). We performed untargeted liquid chromatography with mass spectrometry analysis of plasma to identify analytes associated with liver steatosis. We then performed targeted metabolomic analysis of blood samples from 2 independent cohorts of individuals who underwent annual health examinations in China (1157 subjects with or without diabetes and 767 subjects with or without liver steatosis; replication cohorts). We performed mass spectrometry analysis of plasma from C57BL/6J mice, germ-free, and mice given antibiotics. C57BL/6J mice were given 0.325% (m/v) N,N,N-trimethyl-5-aminovaleric acid (TMAVA) in their drinking water and placed on a 45% high-fat diet (HFD) for 2 months. Plasma, liver tissues, and fecal samples were collected; fecal samples were analyzed by 16S ribosomal RNA gene sequencing. C57BL/6J mice with CRISPR-mediated disruption of the gene encoding γ-butyrobetaine hydroxylase (BBOX-knockout mice) were also placed on a 45% HFD for 2 months. Hepatic fatty acid oxidation (FAO) in liver tissues was determined by measuring liberation of 3H2O from [3H] palmitic acid. Liver tissues were analyzed by electron microscopy, to view mitochondria, and proteomic analyses. We used surface plasmon resonance analysis to quantify the affinity of TMAVA for BBOX. Levels of TMAVA, believed to be a metabolite of intestinal microbes, were increased in plasma from subjects with liver steatosis compared with controls, in the discovery and replication cohorts. In 1 replication cohort, the odds ratio for fatty liver in subjects with increased liver plasma levels of TMAVA was 1.82 (95% confidence interval [CI], 1.14-2.90; P = .012). Plasma from mice given antibiotics or germ-free mice had significant reductions in TMAVA compared with control mice. We found the intestinal bacteria Enterococcus faecalis and Pseudomonas aeruginosa to metabolize trimethyllysine to TMAVA; levels of trimethyllysine were significantly higher in plasma from patients with steatosis than controls. We found TMAVA to bind and inhibit BBOX, reducing synthesis of carnitine. Mice given TMAVA had alterations in their fecal microbiomes and reduced cold tolerance; their plasma and liver tissue had significant reductions in levels of carnitine and acyl-carnitine and their hepatocytes had reduced mitochondrial FAO compared with mice given only an HFD. Mice given TMAVA on an HFD developed liver steatosis, which was reduced by carnitine supplementation. BBOX-knockout mice had carnitine deficiency and decreased FAO, increasing uptake and liver accumulation of free fatty acids and exacerbating HFD-induced fatty liver. Levels of TMAVA are increased in plasma from subjects with liver steatosis. In mice, intestinal microbes metabolize trimethyllysine to TMAVA, which reduces carnitine synthesis and FAO to promote steatosis.


Validation of the electronic cigarette attitudes survey (ECAS) for youth.
Electronic cigarette (e-cigarette) use among adolescents has rapidly increased in recent years, especially among Latinx and non-Latinx Black adolescents. Yet, limited research exists on adolescent attitudes that may contribute to the popularity of these products. This is in part due to the lack of measures focused on assessing adolescent attitudes towards e-cigarette use. The aim of this study was to develop a measure of adolescent e-cigarette use attitudes. The sample consisted mainly of Latinx and non-Latinx Black adolescents. Data were collected from 247 youth (M age = 16.0, SD = 1.2), 63.6% were girls, a majority (69.2%) were non-Latinx Black, and 27.1% were Latinx. The Electronic Cigarette Attitudes Survey (ECAS) is comprised of 12 items reflecting attitudes associated with e-cigarettes, which were derived from prior theoretical, quantitative, and qualitative work with e-cigarette users. To determine the factor structure, a parallel analysis scree plot and an exploratory factor analysis (EFA) of the ECAS was conducted using half of the sample chosen at random (n = 113). Results supported a one-factor solution. A confirmatory factory analysis (CFA) was conducted on the other randomly chosen half of participants (n = 121). Results confirm a one-factor solution. No significant differences were found on ECAS scores based on race/ethnicity or e-cigarette use status (lifetime e-cigarette use vs. no use). The ECAS represents a viable measure for assessing e-cigarette attitudes among youth.


Antagonist properties of arylaminopyridazine GABA derivatives at the Ascaris muscle GABA receptor.
1. In a previous study, it was shown that the potency order for two arylamino-pyridazine derivatives, SR95531 and SR95103, was different in Ascaris suum when compared to vertebrate preparations. SR95531, the most potent analogue at the vertebrate GABAA receptor, was found to be very weak at antagonizing GABA responses in Ascaris, but SR95103, approximately 20 times less potent than SR95531 in vertebrate preparations, was more potent than SR95531 in Ascaris. These results suggested the existence of different accessory binding sites at the Ascaris GABA receptor. 2. To test this hypothesis, the effects of a series of arylaminopyridazine derivatives of GABA on the GABA response in Ascaris suum muscle were investigated using a two-microelectrode current-clamp technique. 3. The results showed that SR42627, a potent antagonist at the GABAA receptor, was one of the weakest analogues in Ascaris muscle. In contrast, SR95132, virtually inactive in vertebrate preparations, was equipotent to SR95103, the most potent analogue of the series in Ascaris muscle. 4. The three most potent analogues in Ascaris, SR95103, SR95132 and SR42666, displace GABA dose-response curves to the right without decreasing the maximal response. The modified Schild plots for these compounds are consistent with a competitive mechanism involving two molecules of GABA and only one molecule of antagonist interacting with the receptor. The estimated dissociation constants for SR95103, SR95132 and SR42666 are, respectively, 64, 65 and 105 mumol l-1. 5. Structure-activity relationships for this series of compounds were examined in Ascaris and compared to those in vertebrates. Substitution on the pyridazine ring in the 4-position, while detrimental for the antagonist potency at the vertebrate GABAA receptor, appears to be a prerequisite for antagonistic activity on the Ascaris muscle GABA receptor. These results are interpreted in terms of the accessory binding site theory of Ariëns, and suggest the existence of different accessory binding sites on the Ascaris GABA receptor.


Murine xenotropic type C viruses. IV. Replication and pathogenesis of ducks.
The xenotropic (X-tropic) mouse type C virus (MuLV) and its pseudotype of murine sarcoma virus (MSV) were inoculated into several fertilized developing Pekin duck eggs. The development of the duck embryos was substantially reduced in those receiving the X-tropic viruses compared to eggs inoculated only with tissue culture medium. Infections virus was isolated from some of the adult animals; in others, evidence for integrated virus sequences in the tissues was noted. No specific pathology was found in the ducks that received X-trophic MuLV alone, but one duck developed multiple fibrosarcomas when inoculated at birth with the X-tropic virus pseudotype of MSV. Two ducks receiving X-tropic MuLv had signs of haematopoietic disorders. In addition, more virus-inoculated animals had evidence of hepatitis and encephalitis than control ducks. Antibody production to X-tropic MuLv was present in several ducks inoculated with virus either in embryo or at birth. Absence of antiviral antibodies was noted in those animals whose tissue contained replicating virus. These studies confirm the observations with X-tropic virus in tissue culture. They demonstrate in vivo that avian species are susceptible to infection by the mouse X-tropic virus and that their fibroblasts can be transformed by the X-tropic MuLV pseudotype of MSV.


HDAC9 regulates ox-LDL-induced endothelial cell apoptosis by participating in inflammatory reactions.
Atherosclerosis is the most common cause of cardiovascular diseases worldwide. The endothelial cell apoptosis elicited by oxidized low-density lipoprotein (ox-LDL), which contributes to endothelial damage and inflammation, is a particularly important event in the early stage of atherosclerosis. However, the mechanism underlying ox-LDL-induced endothelial cell apoptosis remains unclear. Here we found that HDAC9 expression was increased at both the mRNA and protein levels accompanied by dose-dependent ox-LDL-induced endothelial cell apoptosis. Depletion of HDAC9 by its specific shRNA significantly antagonized ox-LDL-induced cell apoptosis and suppressed the expression of ox-LDL-induced inflammatory factors, such as TNF-alpha and MCP1. These data suggest that HDAC9 is an important epigenetic factor regulating ox-LDL-induced endothelial cell apoptosis and inflammatory factor expression. These results suggest that HDAC9 may participate in ox-LDL-induced endothelial damage and inflammation during atherosclerosis development.


[Performing an arterial or venous puncture: its meaning for the Pediatric ICU Nursing team].
A preliminary note of a qualitative research using Symbolic Interactionism as theoretical framework and Ground Theory as methodological framework, carried out with nurses, technicians and nursing assistants of a Pediatric Intensive Care Unit (PICU). The study aimed at understanding the meaning that performing an arterial or venous puncture in children hospitalized at PICU for the nursing team. Preliminary data analysis revealed that the puncture is seen by the PICU nursing team as an important procedure--stressful for the child, family and team--but if performed promptly, such procedure can be good for the personal and professional ego.


Age-related insulin resistance: is it an obligatory finding? The lesson from healthy centenarians.
It is widely known that advancing age is associated with impaired glucose handling. A unifying hypothesis explaining the relationship between aging and insulin resistance might encompass four main pathways, namely: (a) anthropometric changes (relative and absolute increase in body fat combined with a decline in fat free mass) which could be the anatomic substrate for explaining the reduction in active metabolic tissue; (b) environmental causes, mainly diet style and physical activity; (c) neuro-hormonal variations [decline in plasma dehydroepandrosterone sulphate (DHEAS) and IGF-1]; and finally (d) the rise in oxidative stress. Indeed previous studies have also investigated the occurrence and the degree of insulin resistance in healthy centenarians. Such data demonstrated that age-related insulin resistance is not an obligatory finding in the elderly and that healthy centenarians have a preserved insulin action compared to aged subjects. Why insulin action is preserved in centenarians is still not known. Nevertheless, a possible approach to the question is to outline the centenarians' anthropometric, endocrine and metabolic characteristics in order to design a clinical picture of such metabolic "successful aging". According to the remodeling theory of age, the preserved insulin action in centenarians might be the net result of the continuous adaptation of the body to the deleterious changes that occur over time. Nevertheless, only future longitudinal studies specifically designed to investigate the relationship between extreme old age and degree of insulin sensitivity will provide a conclusive answer with regard to the pathophysiology of adaptive metabolic changes occurring in the elderly.


Urease activity in the rumen of sheep and the isolation of ureolytic bacteria.
Urease activity in the sheep rumen varied with the diet of the sheep, but appeared to be largely or entirely present in the small bacterial fraction. Screening of over 1000 strains of rumen bacteria isolated on different media showed that urease activity was apparently confined to species of Staphylococcus, Lactobacillus casei var. casei and Klebsiella aerogenes. Consideration of the numbers in which these occurred and their activities suggested that the bacteria could not be responsible for the total rumen urease activity. By enrichment culture a ureolytic strain of Streptococcus faecium was isolated. This had a higher urease activity than the other bacteria and occurred in higher numbers in the rumen. It could live with other bacteria in the rumen of a gnotobiotic lamb in numbers, and with a urease activity, comparable with those in the normal sheep rumen. The other properties of the bacterium also suggested that it would grow and produce urease in the rumen, but was unlikely to retain its urease activity after isolation. It was concluded that this bacterium was the main source of rumen urease in roughage-fed, and probably other, sheep.


Optical interference coatings: introduction by the feature editors.
This introduction briefly reviews the history of the series of topical meetings on optical interference coatings and defines the scope of the features in this 15 July 1989 issue on the papers from the Fourth Topical Meeting.


Perceptions of Problems with Household Insects: Qualitative and Quantitative Findings from Peri-Urban Communities in Arequipa, Peru.
Vector-borne diseases continue to impose a major health burden on Peru and neighboring countries. The challenge of addressing vector-borne disease is compounded by changing social, economic, and climatic conditions. Peri-urban Arequipa is an important region to study insect infestations because of ongoing challenges with disease vectors such as triatomines and a variety of other insects. We conducted surveys (N = 1,182) and seven focus groups (average seven participants) in peri-urban Arequipa to explore knowledge of and perception toward various insects that infest the region. Focus group participants reported the presence of a wide variety of insects in and around the home, including disease vectors such as triatomines (also identified by 27.2% of survey households), mosquitoes, spiders, and bed bugs, as well as nuisance insects. Health concerns related to insects included vector-borne diseases, spider bites, allergies, and sequelae from bed bug bites, and hygiene concerns. A majority of participants in the quantitative surveys identified triatomines as the insect they were most worried about (69.9%) and could identify Chagas disease as a health risk associated with triatomines (54.9%). Insect infestations in peri-urban Arequipa present multiple burdens to residents, including injury and illness from triatomines and other insects, as well as potential mental and economic concerns related to insects such as bed bugs. Future initiatives should continue to address triatomine infestations through educational outreach and implement a more holistic approach to address the burden of both disease and nuisance insects.


Spatial distribution of mechanical properties in Pseudomonas aeruginosa biofilms, and their potential impacts on biofilm deformation.
The mechanical properties of biofilms can be used to predict biofilm deformation under external forces, for example, under fluid flow. We used magnetic tweezers to spatially map the compliance of Pseudomonas aeruginosa biofilms at the microscale, then applied modeling to assess its effects on biofilm deformation. Biofilms were grown in capillary flow cells with Reynolds numbers (Re) ranging from 0.28 to 13.9, bulk dissolved oxygen (DO) concentrations from 1 mg/L to 8 mg/L, and bulk calcium ion (Ca2+ ) concentrations of 0 and 100 mg CaCl2 /L. Higher Re numbers resulted in more uniform biofilm morphologies. The biofilm was stiffer at the center of the flow cell than near the walls. Lower bulk DO led to more stratified biofilms. Higher Ca2+ concentrations led to increased stiffness and more uniform mechanical properties. Using the experimental mechanical properties, fluid-structure interaction models predicted up to 64% greater deformation for heterogeneous biofilms, compared with a homogeneous biofilms with the same average properties. However, the deviation depended on the biofilm morphology and flow regime. Our results show significant spatial mechanical variability exists at the microscale, and that this variability can potentially affect biofilm deformation. The average biofilm mechanical properties, provided in many studies, should be used with caution when predicting biofilm deformation.


DC-electrical penetration graph waveforms for Dalbulus maidis (Hemiptera: Cicadellidae) and the effects of entomopathogenic fungi on its probing behavior.
The corn leafhopper Dalbulus maidis is an important transmitter of viruses and bacteria to maize plants. Data on the stylet probing and ingestion behavior of D. maidis, gathered using the DC-electrical penetration graph (DC-EPG) technique, are limited. The increasing prevalence of this pest and the diseases that it transmits in maize crops heighten the importance of studying how control tools affect the probing behavior of these insects, to reduce or prevent the chances of pathogen transmission and the damage from feeding. Our study recorded stylet activities of D. maidis, using a DC-EPG system and compared the appearances of waveforms with those from published AC and AC-DC EPG studies. All types of systems produced similar waveform appearances; therefore, we used the waveform nomenclature previously published. We also determined the effects of the entomopathogenic fungus Cordyceps javanica on the probing behavior of D. maidis at different time points after the fungus was applied by spraying. Forty-eight hours after the insects were sprayed, the effects were pronounced, with significant disruption of the stylet activities in phloem and non-phloem phases. Our study indicated that this commercial microbiological product, with the active ingredient C. javanica, can alter the probing behavior of D. maidis and may be helpful in management of the vector.


Resistive Pulse Sensing on a Capillary-Assisted Microfluidic Platform for On-Site Single-Particle Analyses.
Capillary-assisted flow is valuable for utilizing microfluidics-based electrical sensing platforms at on-site locations by simplifying microfluidic operations and system construction; however, incorporating capillary-assisted flow in platforms requires easy microfluidic modification and stability over time for capillary-assisted flow generation and sensing performance. Herein, we report a capillary-assisted microfluidics-based electrical sensing platform using a one-step modification of polydimethylsiloxane (PDMS) with polyethylene glycol (PEG). As a model of electrical sensing platforms, this work focused on resistive pulse sensing (RPS) using a micropore in a microfluidic chip for label-free electrical detection of single analytes, and filling the micropore with an electrolyte is the first step to perform this RPS. The PEG-PDMS surfaces remained hydrophilic after ambient storage for 30 d and assisted in generating an electrolyte flow for filling the micropore with the electrolyte. We demonstrated the successful detection and size analysis of micrometer particles and bacterial cells based on RPS using the microfluidic chip stored in a dry state for 30 d. Combining this capillary-assisted microfluidic platform with a portable RPS system makes on-site detection and analysis of single pathogens possible.


Semi-supervised Medical Image Segmentation with Multiscale Contrastive Learning and Cross-Supervision.
We propose a semi-supervised segmentation method based on multiscale contrastive learning to solve the problem of shortage of annotations in medical image segmentation tasks. We apply perturbations to the input image and encoded features and make the output as consistent as possible by cross-supervision, which is a way to improve the generalizability of the model. Two scales of contrastive learning, patch-level and pixel-level, are employed to enhance the intra-class compactness and inter-class separability of the features. We evaluate the proposed model using three public datasets for brain tumor,left atrial, and cellular nuclei segmentation. The experiments showed that our model outperforms state-of-the-art methods.Clinical relevance- The proposed method can be used for medical image segmentation with limited annotated data and achieve comparable performance to the fully annotated situation. Such an approach can be easily extended to other clinical applications.


Plasma homocysteine concentration is decreased by dietary intervention.
High plasma total homocysteine (tHcy) concentration is reported to be a risk factor for vascular diseases. We investigated the extent to which serum folate and plasma tHcy respond to a high intake of natural folate from food. Thirty-seven healthy females volunteered t o participate in a crossover dietary intervention. The study included a baseline period and two 5-week diet periods (low- and high-folate diets) with a 3-week washout in between. The low-folate diet contained one serving of both vegetables and fruit/d, while during the high-folate diet the subjects ate at least seven servings of vegetables, berries, and citrus fruit/d. Serum and erythrocyte (RBC) folate, serum vitamin B (12), and plasma tHcy concentrations were measured at the base-line and at the end of each diet period. The mean concentrations of serum and RBC folate were 11.0 (SD 3.0) nmol/l and 412 (SD 120) nmol/l at the end of the low-folate diet and 78 (95 % CI 62, 94) % and 14 (95 % CI 8, 20) % higher in response to the high-folate diet (P< 0.001). The serum concentration of vitamin B12 remained unchanged during the intervention. The mean plasma tHcy concentration was 8.0 pmol/ at the end of the low-folate diet and decreased by 13 (95% CI 9, 18) % in response to the high-folate diet (P<0.001). In conclusion, a diet high in fresh berries, citrus fruit, and vegetables effectively increases serum and RBC folate and decreases plasma homocysteine.


[The concentration of Tamsulosin hydrochloride in the blood and prostatic tissue of the patients in benign prostatic hyperplasia].
The penetration of Tamsulosin hydrochloride into the blood and the prostatic tissue was examined. Fifty-two patients with benign prostatic hyperplasia treated with transurethral resection of the prostate were entered in this study. This drug was administered orally in a dose of 2.0 mg once a day for 7 to 179 days preoperatively. The blood samples were taken simultaneously at the time of the prostatic tissue sampling. 1. The correlation coefficient was hardly significant between aging and concentration of the drug in the blood or in the prostatic tissue. 2. The correlation coefficient was hardly significant between the duration of the drug administration and concentration of the drug in the blood or the prostatic tissue. 3. The correlation coefficient was significant between the concentration of the drug in the blood and the prostatic tissue. 4. The fifty-two patients showed no significant adverse reactions during administration of the drug. These results suggest that the drug can be administered safely to the aged even in a long-term and can be penetrated into the blood and the prostatic tissue with a positive correlation.


A single-chain bifunctional gonadotropin analog is secreted from Chinese hamster ovary cells as two distinct bioactive species.
One of the major developments in exploring structure activity relationships of the glycoprotein hormone family was the genetic engineering of single chains comprised of the common alpha subunit and one or more of the hormone-specific beta subunits tandemly arranged. These studies indicate that there is a structural permissiveness in the quaternary relationships between the subunits and biological activity. However, the conformational relationships between the ligand and the receptor are unclear. Bifunctional triple-domain analogs represent an ideal model to address this issue. Does a single molecule possess the ability to simultaneously interact with both specific receptors or are there two functionally distinct species in the chimeric population? Here we show, using a preadsorption protocol comprised of Chinese hamster ovary cells expressing either the luteinizing hormone (LH)/chorionic gonadotropin (CG) or follicle-stimulating hormone (FSH) receptor, that at least two distinct bioactive populations of the dually active triple-domain chimera FSHbeta-CGbeta-alpha are synthesized, each corresponding to a single activity (CG or FSH). Furthermore, we show that these bioactive populations form distinct stable heterodimer-like contacts. That there is not a single biologically active species formed during synthesis of the chimera implies that in vivo the heterodimer exists in multiple conformations and is not a static rigid molecule.


Expression of mutated p53 occurs in tumor-distant epithelia of head and neck cancer patients: a possible molecular basis for the development of multiple tumors.
As in most other tumor types, expression of mutated or phenotypically altered p53 is a common occurrence in head and neck carcinogenesis. Since the prognosis for many head and neck tumor patients is severely affected by the occurrence of multiple primary and secondary tumors, we have analyzed the phenotype and genotype of p53 in squamous and respiratory epithelia either adjacent to or at significant distance from the primary tumors. Many tumor patients showed multifocal overexpression of the p53 protein in a variety of these epithelia. Overexpression of p53 correlated with increased proliferation and dedifferentiation, as demonstrated by immunohistochemistry and in situ hybridization using histone H3 and cytokeratin-specific probes. Polymerase chain reaction-single-strand conformation polymorphism analysis and sequencing of p53 DNA, amplified from these biopsies after immunostaining and microdissection, confirmed and extended these findings. We have identified different mutations in p53 in different tumor-distant epithelia from the same patients. The data indicate that mutation of p53 is an early event in head and neck carcinogenesis, preceding signs of overt neoplasia, and that different mutations in p53 in multiple foci may provide a molecular basis for the development of multiple tumors.


Male-specific DNA markers provide genetic evidence of an XY chromosome system, a recombination arrest and allow the tracing of paternal lineages in date palm.
Whether sex chromosomes are differentiated is an important aspect of our knowledge of dioecious plants, such as date palm (Phoenix dactylifera). In this crop plant, the female individuals produce dates, and are thus the more valuable sex. However, there is no way to identify the sex of date palm plants before reproductive age, and the sex-determining mechanism is still unclear. To identify sex-linked microsatellite markers, we surveyed a set of 52 male and 55 female genotypes representing the geographical diversity of the species. We found three genetically linked loci that are heterozygous only in males. Male-specific alleles allowed us to identify the gender in 100% of individuals. These results confirm the existence of an XY chromosomal system with a nonrecombining XY-like region in the date palm genome. The distribution of Y haplotypes in western and eastern haplogroups allowed us to trace two male ancestral paternal lineages that account for all known Y diversity in date palm. The very low diversity associated with Y haplotypes is consistent with clonal paternal transmission of a nonrecombining male-determining region. Our results establish the date palm as a biological model with one of the most ancient sex chromosomes in flowering plants.


[Microbiological rationale for using whey on salting salmon caviar].
The paper provides a rationale for the use of whey to salt salmon fishes instead of traditional preservatives, including those exported from low industrial potential countries, which do not undergo comprehensive sanitary and hygienic tests. On the basis of the performed studies, the authors recommend to use whey to salt salmon caviar, which ensures the ecological purity of the product containing the minimum amount of preservatives and other substances that fail to affect its organoleptic properties.


Gray matter morphological abnormities are constrained by normal structural covariance network in OCD.
A growing body of evidences reveal that abnormal gray matter morphology is constrained by normal brain network architecture in neurodegenerative and psychiatric disorders. However, whether this finding holds true in obsessive-compulsive disorder (OCD) remains unknown. In the current study, we aimed to investigate the association between gray matter morphological abnormities and normal structural covariance network architecture in OCD. First, gray matter morphological abnormities were obtained between 98 medicine-naive and first-episode patients with OCD and 130 healthy controls (HCs). Then, putative disease epicenters whose structural connectome profiles in HCs most resembled the morphological differences pattern were identified using a backfoward stepwise regression analysis. A set of brain regions were identified as putative disease epicenters whose structural connectome architecture significantly explained 59.94% variance of morphological abnormalities. These disease epicenters comprised brain regions implicated in high-order cognitive functions and sensory/motor processing. Other brain regions with stronger structural connections to disease epicenters exhibited greater vulnerability to disease. Together, these results suggest that gray matter abnormities are constrained by structural connectome and provide new insights into the possible pathological progression in OCD.


Global theory and the nature of risk, Part I. How orthodox managed care stifles innovation.
The growing awareness that managed care is rapidly unraveling has not only produced a good deal of alarm, but also a call for prognostications regarding the future. Unfortunately, old habits die hard, and wedded ideologies die even harder. Instead of paving the way for innovation, most managed care pundits refuse to read the tea leaves properly and acknowledge that the orthodox regime is irretrievably comatose. Not understanding the fundamental flaws inherent in the old model, many persevere with rehashed predictions that only echo the very non-starters that got us in the present jam in the first place. Managed care has so far focused its energies on integrating the wrong objects, insurance and care, with all the predictably bad effects. Part 2 of this article will explore what this means and introduce the global theory of managed care as an alternative vision. Global theory lays a new foundation based on a more sound microeconomic model of risk, bifurcated markets, global fees for integrated episodes of care, and most important of all, patient/physician sovereignty.


Treatment and survival following in-hospital cardiac arrest: does patient ethnicity matter?
Previous research on racial/ethnic disparities in relation to cardiac arrest has mainly focused on black vs. white disparities in the USA. The great majority of these studies concerns out-of-hospital cardiac arrest (OHCA). The current nationwide registry study aims to explore whether there are ethnic differences in treatment and survival following in-hospital cardiac arrest (IHCA), examining possible disparities towards Middle Eastern and African minorities in a European context. In this retrospective registry study, 24 217 patients from the IHCA part of the Swedish Registry of Cardiopulmonary Resuscitation were included. Data on patient ethnicity were obtained from Statistics Sweden. Regression analysis was performed to assess the impact of ethnicity on cardiopulmonary resuscitation (CPR) delay, CPR duration, survival immediately after CPR, and the medical team's reported satisfaction with the treatment. Middle Eastern and African patients were not treated significantly different compared to Nordic patients when controlling for hospital, year, age, sex, socioeconomic status, comorbidity, aetiology, and initial heart rhythm. Interestingly, we find that Middle Eastern patients were more likely to survive than Nordic patients (odds ratio = 1.52). Overall, hospital staff do not appear to treat IHCA patients differently based on their ethnicity. Nevertheless, Middle Eastern patients are more likely to survive IHCA.


iBench: A ground truth approach for advanced validation of mass spectrometry identification method.
The discovery of many noncanonical peptides detectable with sensitive mass spectrometry inside, outside, and on cells shepherded the development of novel methods for their identification, often not supported by a systematic benchmarking with other methods. We here propose iBench, a bioinformatic tool that can construct ground truth proteomics datasets and cognate databases, thereby generating a training court wherein methods, search engines, and proteomics strategies can be tested, and their performances estimated by the same tool. iBench can be coupled to the main database search engines, allows the selection of customized features of mass spectrometry spectra and peptides, provides standard benchmarking outputs, and is open source. The proof-of-concept application to tryptic proteome digestions, immunopeptidomes, and synthetic peptide libraries dissected the impact that noncanonical peptides could have on the identification of canonical peptides by Mascot search with rescoring via Percolator (Mascot+Percolator).


Natural and forced neurogenesis in the adult brain: Mechanisms and their possible application to treat neurological disorders.
Neural stem cells (NSCs) in the adult hippocampus generate new neurons via a process referred to as neurogenesis, supporting cognitive functions. Since altered neurogenesis has been reportedly associated with several diseases such as epilepsy, the molecular basis of NSC activity is an important focus in the study of neurogenesis. Furthermore, facilitation of neurogenesis in the injured brain would be an ideal approach to replenish lost neurons for damage recovery. However, natural neurogenesis by endogenous NSCs in the adult brain is insufficient for complete recovery after severe injury. Recent advances in understanding forced neurogenesis from brain-resident non-neuronal cells by direct reprogramming and clearing hurdles to achieve it have improved the ability to replace damaged neurons in the brain. In this review, we describe molecular mechanisms underlying natural and forced neurogenesis, and discuss future directions for treatments of diseases in the central nervous system.


Impact of dietary macronutrient distribution on BMI and cardiometabolic outcomes in overweight and obese children and adolescents: a systematic review.
The present systematic review examined the effectiveness of weight management interventions comparing diets with varying macronutrient distributions on BMI and cardiometabolic risk factors in overweight or obese children and adolescents. A systematic search of seven databases for the period 1975-2013 identified 14 eligible randomized or quasi-randomized controlled trials conducted with 6-18-year-old subjects. Seven trials compared a low-fat (≤ 33% energy or < 40 g/day) to an isocaloric (n = 2) or ad libitum (n = 5) low-carbohydrate diet (< 20% energy or < 60 g/day). Meta-analysis indicated a greater reduction in BMI in the low-carbohydrate group immediately after dietary intervention; however, the quality of the studies was limited and cardiometabolic benefits were inconsistent. Six trials compared increased-protein diets (19-30% energy) to isocaloric standard-protein diets (15-20% energy) and one compared an increased-fat diet (40% energy) to an isocaloric standard-fat diet (27% energy); there were no differences in outcomes in these studies. Current evidence suggests that improved weight status can be achieved in overweight or obese children and adolescents irrespective of the macronutrient distribution of a reduced-energy diet. Tailoring the macronutrient content to target specific cardiometabolic risk factors, such as a low-carbohydrate diet to treat insulin resistance, may be possible, but further research is needed before specific recommendations can be made.


Direct Access to Functional (Meth)acrylate Copolymers through Transesterification with Lithium Alkoxides.
A straightforward and efficient synthetic method that transforms poly(methyl methacrylate) (PMMA) into value-added materials is presented. Specifically, PMMA is modified by transesterification to produce a variety of functional copolymers from a single starting material. Key to the reaction is the use of lithium alkoxides, prepared by treatment of primary alcohols with LDA, to displace the methyl esters. Under optimized conditions, up to 65% functionalization was achieved and copolymers containing alkyl, alkene, alkyne, benzyl, and (poly)ether side groups could be prepared. The versatility of this protocol was further demonstrated through the functionalization of both PMMA homo and block copolymers obtained through either radical polymerization (traditional and controlled) or anionic procedures. The scope of this strategy was illustrated by extension to a range of architectures and polymer backbones.


Septal wall motion. Its significance on outcome of left ventricular scar resection.
To assess the importance of septal wall motion on patient outcome after resection of large akinetic and dyskinetic segments of left ventricle, the records of 70 patients undergoing left ventricular scar excision alone or in combination with myocardial revascularization procedures between January 1970 and January 1977 were reviewed. Patients requiring simultaneous prosthetic valve replacement were excluded. Preoperative left anterior oblique ventriculograms categorized this series of patients into two distinct groups, group A (36 patients) having normal septal wall motion and group B (34 patients) having akinetic or dyskinetic septal walls. Indications for operation and preoperative ejection fractions were similar in both groups. Analysis of these patients subjected to surgery with and without preoperative evidence of septal wall motion demonstrated no significant difference in either functional clinical capacity or in mortality. Mortality for both groups was 11%. Absence of ventricular septal wall motion has no significant effect on outcome of left ventricular scar resection and should not be used as a contraindication to surgery.


New staging system for sinonasal inverted papilloma in the endoscopic era.
Advanced endoscopic techniques have emerged as the preferred treatment modality for sinonasal inverted papilloma (IP); however, a staging system that provides prognostic information has not yet been developed. This study aims to develop a clinically relevant staging system for IP managed with the endoscopic approach as the primary surgical modality. A systematic review of the English-language literature (1985-2006) and a single institution's experience. From the literature, 445 patients with IP treated by endoscopic resection were identified in 14 reports. Only patients with known IP sites and outcomes were included. Patients were categorized into three groups on the basis of recurrence rates (RR): group A (IP confined to the nasal cavity, ethmoid sinus, and medial maxillary sinus), 3.0% RR (n = 234); group B (IP with lateral maxillary sinus, sphenoid sinus, or frontal sinus involvement), 19.8% RR (n = 177); and group C (IP with extrasinus extension), 35.3% RR (n = 34). Pearson's chi-square test showed statistically significant differences for all pair-wise comparisons between groups (P < .05). Mean follow-up was 39.8 months. This new staging system for IP provides information about prognosis (as operationally defined by RR) for IP managed by advanced endoscopic techniques. In contrast, other staging systems for IP reflect surgeon's judgment rather than outcomes data. This new classification for IP provides important objective data for preoperative planning and patient counseling.


Molecular dynamics simulations of phospholipid bilayers with cholesterol.
To investigate the microscopic interactions between cholesterol and lipids in biological membranes, we have performed a series of molecular dynamics simulations of large membranes with different levels of cholesterol content. The simulations extend to 10 ns, and were performed with hydrated dipalmitoylphosphatidylcholine (DPPC) bilayers. The bilayers contain 1024 lipids of which 0-40% were cholesterol and the rest DPPC. The effects of cholesterol on the structure and mesoscopic dynamics of the bilayer were monitored as a function of cholesterol concentration. The main effects observed are a significant ordering of the DPPC chains (as monitored by NMR type order parameters), a reduced fraction of gauche bonds, a reduced surface area per lipid, less undulations--corresponding to an increased bending modulus for the membrane, smaller area fluctuations, and a reduced lateral diffusion of DPPC-lipids as well as cholesterols.


Synthesis and characterization of the ultramarine-type analog Na(8-x)[Si6Al6O24] x (S2,S3,CO3)(1-2).
The use of nitrite sodalite as a precursor to prepare new blue ultramarine analogs has been investigated. The encapsulation of the chromophores inside of beta cages was achieved by heating the nitrite sodalite precursor with a mixture of sodium carbonate, sulfur, and a reducing agent at about 1000 K under airtight conditions. The obtained new blue ultramarine-type material was characterized by means of X-ray and neutron powder diffraction, transmission electron microscopy, 29Si magic-angle-spinning NMR, IR, Raman, and diffuse reflectance spectroscopies. Thermogravimetric analysis and magnetic measurements were performed in order to determine water and chromophore contents, respectively. On the basis of the spectroscopic results and Rietveld analysis of neutron powder data, the beta cage filling was found to be yellow S2(-) and blue S3(-) chromophores along with carbonate anions. The determined chromophore concentration, about 0.31 mol per formula unit, is enough to have greenish-blue ultramarines, which proves that ultramarine analogs can be obtained from nitrite sodalite.


Role of human hypoxanthine guanine phosphoribosyltransferase in activation of the antiviral agent T-705 (favipiravir).
6-Fluoro-3-hydroxy-2-pyrazinecarboxamide (T-705) is a novel antiviral compound with broad activity against influenza virus and diverse RNA viruses. Its active metabolite, T-705-ribose-5'-triphosphate (T-705-RTP), is recognized by influenza virus RNA polymerase as a substrate competing with GTP, giving inhibition of viral RNA synthesis and lethal virus mutagenesis. Which enzymes perform the activation of T-705 is unknown. We here demonstrate that human hypoxanthine guanine phosphoribosyltransferase (HGPRT) converts T-705 into its ribose-5'-monophosphate (RMP) prior to formation of T-705-RTP. The anti-influenza virus activity of T-705 and T-1105 (3-hydroxy-2-pyrazinecarboxamide; the analog lacking the 6-fluoro atom) was lost in HGPRT-deficient Madin-Darby canine kidney cells. This HGPRT dependency was confirmed in human embryonic kidney 293T cells undergoing HGPRT-specific gene knockdown followed by influenza virus ribonucleoprotein reconstitution. Knockdown for adenine phosphoribosyltransferase (APRT) or nicotinamide phosphoribosyltransferase did not change the antiviral activity of T-705 and T-1105. Enzymatic assays showed that T-705 and T-1105 are poor substrates for human HGPRT having Km(app) values of 6.4 and 4.1 mM, respectively. Formation of the RMP metabolites by APRT was negligible, and so was the formation of the ribosylated metabolites by human purine nucleoside phosphorylase. Phosphoribosylation and antiviral activity of the 2-pyrazinecarboxamide derivatives was shown to require the presence of the 3-hydroxyl but not the 6-fluoro substituent. The crystal structure of T-705-RMP in complex with human HGPRT showed how this compound binds in the active site. Since conversion of T-705 by HGPRT appears to be inefficient, T-705-RMP prodrugs may be designed to increase the antiviral potency of this new antiviral agent.


[Fetal hydronephrosis. Case report and literature review].
Fetal hydronephrosis is the most common congenital anomaly detected by routine prenatal ultrasound. It is the abnormal dilatation of the urinary canal, and its most frequent causes are physiologic and transitory hydronephrosis, with spontaneous resolution. Pelvi-ureteric junction obstruction represents its first pathological cause. Renal function worsening is its major complication. During pre and post-natal periods ultrasound is the election diagnostic method for this entity. The two most accepted criteria to defining hydronephrosis are Society for Fetal Urology grade and anterior-posterior diameter of renal pelvis. Here we present a case of unilateral fetal hydronephrosis detected at 31" gestational week, its pre and postnatal ultrasound control, and obstetric and neonatal treatment. Prenatal opportune diagnosis and adequate postnatal treatment (medical or surgical) are very important to preserve renal function.


A robust cage-based framework for the highly selective purification of natural gas.
A robust microporous material (FJI-H19), which is constructed from distorted cuboctahedral cages and distorted octahedral cages, has been successfully synthesized. FJI-H19 possesses good thermal and water stability as well as highly selective adsorption of C3 and C4 hydrocarbons over CH4 under ambient conditions. More importantly, the high selectivities for the separation of CH4/C3 or C4 mixtures (85/15) have not only been estimated by ideal adsorbed solution theory (IAST) but also definitely confirmed by breakthrough experiments.


Immune response and possible therapeutics in COVID-19.
COVID-19 has emerged as a pandemic affecting about 213 countries in all the continents of the globe, resulting in more than 37.8 million individuals getting infected and over 1.08 million deaths worldwide, jeopardizing global human health and the economy. This presents an urgent need to develop therapies that target the SARS-CoV2 virus specifically. This review aims at presenting the available information on the coronavirus disease 2019 along with various drugs that are having widespread use until a vaccine candidate is available to aid in the development of therapeutic strategies against COVID-19.


Imitating by Generating: Deep Generative Models for Imitation of Interactive Tasks.
To coordinate actions with an interaction partner requires a constant exchange of sensorimotor signals. Humans acquire these skills in infancy and early childhood mostly by imitation learning and active engagement with a skilled partner. They require the ability to predict and adapt to one's partner during an interaction. In this work we want to explore these ideas in a human-robot interaction setting in which a robot is required to learn interactive tasks from a combination of observational and kinesthetic learning. To this end, we propose a deep learning framework consisting of a number of components for (1) human and robot motion embedding, (2) motion prediction of the human partner, and (3) generation of robot joint trajectories matching the human motion. As long-term motion prediction methods often suffer from the problem of regression to the mean, our technical contribution here is a novel probabilistic latent variable model which does not predict in joint space but in latent space. To test the proposed method, we collect human-human interaction data and human-robot interaction data of four interactive tasks "hand-shake," "hand-wave," "parachute fist-bump," and "rocket fist-bump." We demonstrate experimentally the importance of predictive and adaptive components as well as low-level abstractions to successfully learn to imitate human behavior in interactive social tasks.


Predictors of falls among postmenopausal women: results from the National Osteoporosis Risk Assessment (NORA).
Using data from 66,134 postmenopausal women enrolled in the National Osteoporosis Risk Assessment (NORA) study, more than half of whom were less than age 65, we identified 18 risk factors that independently predicted a significantly increased risk of falling and observed a graded increase in risk with an increasing number of risk factors. This study was designed to identify predictors of falls in a large prospective study of community-dwelling, postmenopausal women, 58% of whom were less than 65 years old at baseline. We exclusively used survey data from 66,134 NORA participants who completed the baseline survey and three follow-up surveys over 6 years. Stepwise logistic regression was used to select potential fall predictors. A simple fall risk index was created by giving one point to each significant independent risk factor. More than one third (38.2%) of participants reported at least one fall since baseline. The largest predictor of fall risk was history of falls (odds ratio [OR] = 2.7). In the multivariate analysis, 17 additional risk factors were significantly associated with incident falls (but with smaller OR), including age, college education, poor hearing, diabetes, personal or family history of fracture, hypothyroidism, and height loss. Of the 3,346 women with zero fall risk factors, 22.6% reported falling compared to 84.3% of the 51 women with >or=11 risk factors. This large cohort had sufficient power to identify 18 risk factors that independently predicted a significantly increased risk of falling with a graded increase in risk with increasing number of risk factors.


Spatial distributions of ozonolysis products from human surfaces in ventilated rooms.
Ozone has adverse effects on human health. Skin oil on the human surface acts as an ozone sink indoors, producing oxidation products that can cause skin and respiratory irritations. Concentrations of ozone and oxidation products near human surfaces, including the breathing zone, can be modulated by indoor ventilation modes and human surface conditions. The objective of this study is to examine concentrations and spatial heterogeneity of ozone and ozonolysis products under representative ranges of indoor ventilation, clothing, and breathing conditions. Using computational fluid dynamics (CFD) simulation in conjunction with a chemical kinetic model, details of ozone reactions with the human surface and subsequent chemical reactions are examined. The results show that primary ozonolysis products are concentrated near the soiled clothing, while the secondary products are relatively well distributed throughout the room. Increasing indoor air mixing enhances the ozone deposition to the human surface, thereby resulting in higher emission rates of oxidation products in the room. Soiled clothing consumes more ozone than clean clothing and accordingly produces ~ 65% more primary products and ~15% more secondary products. The results also reveal that unsaturated hydrocarbons from the human breath, such as isoprene, contribute to only ~0.5% of ozone removal compared to ozone deposition to the human surface.


Localization of antibody-binding sites by sequence analysis of cloned pilin genes from Neisseria gonorrhoeae.
Immunological analysis of gonococcal pilin (the protein structural subunit of pili) has demonstrated the existence of cross-reacting and type-specific epitopes. The role in adhesion of the domains represented by these epitopes remains unclear. DNA sequencing of a series of pilin-expressing (pilE) genes from a number of otherwise isogenic pilus antigenic variants combined with previous immunological analysis of the corresponding encoded pilins has allowed us to correlate certain predicted amino acid sequences with monoclonal antibody reactivities. The putative epitopes for type-specific antibodies lie predominantly in hydrophilic domains that also contain beta turns. The epitopes for type-specific monoclonal antibodies were shown to depend on amino acid changes either in three separated blocks of amino acid sequence in the semi-variable (SV) region of pilin, or in discrete regions that lie in the disulphide loop in the hypervariable (HV) region of the polypeptide. In contrast, antibody SM1, which reacts with all gonococcal pili, recognizes a poorly immunogenic region of moderate hydrophilicity but low turn potential lying in a conserved portion of the pilin molecule. Our results confirm that antibodies directed against epitopes in both the SV and HV regions are able to inhibit adhesion.


[A sonde-free method of studying the acid-forming and evacuatory functions of the stomach].
The authors have developed and validated the use of a tube-free method for examining gastric function, with acidotest dragees (2,4-diamino-4-ethoxyazobenzene) manufactured by Hinoin, Hungary, used as the acidity indicator. Parallel studies by intragastric pH-metry and x-ray examination of the stomach were carried out in 630 normal subjects and patients with gastroduodenal diseases. The findings evidence that the tube-free method permits assessing the acid-producing, evacuatory, and acid-neutralizing functions of the stomach during and between digestion secretion periods. Criteria for the assessment and normal values were defined as were the diagnostic potentialities of the method. This technique may be widely used in practical medicine, particularly in mass screenings of adults and children, in diagnostic examinations, and in assessment of the treatment efficacy.


[Assessment of a carcinogenic risk to the population of Bratsk].
The paper provides data on the assessment of a carcinogenic risk to the population of Bratsk, a large industrial center. Long-term ambient air pollution with 3,4-benz(a)pyrene, formaldehyde, chromium, and other impurities causes the inadmissible level of a risk that has some differences for dwellers in some districts of the town. Clinical and immunological studies of an apparently healthy population revealed the tension of defensive immune mechanisms in the residents who were more exposed to pollution. Comparison of the level of breast cancer oncomarkers, neurospecific enolase in the sera of populations in the differently carcinogenic areas enables the level of man-made exposure to be considered as a significant risk factor.


Hospital and medical staff strategic planning: developing an integrated approach.
The physician as the principal customer of the hospital is a relatively new concept, indicative of the shift to a more complete market orientation in strategic planning. Although medical staff and medical community dynamics receive increasing attention in strategic planning, much more sophistication is now needed to involve physicians constructively in strategic planning for the hospital and medical staff. While full consonance of physician and hospital plans may be achievable only in a completely integrated delivery system, there is considerable room for improvement in current organizational models.


Experimental induction of cutaneous streptococcal abscesses in swine as a sequela to swinepox.
Streptococcal abscesses were experimentally induced in skin of swine as a sequela to swinepox. Swinepox lesions were more uniform in distribution when infection was induced by IV injection of swinepox virus than when induced by lice (Haematopinus suis) or scarification of skin. The incubation period for swinepox was between 10 and 14 days when virus was administered IV. Cutaneous abscesses developed in swine given IV injection of streptococci 10 and 14 days after they were injected with swinepox virus, but not when they were given the streptococci 7 days after virus injection or simultaneously with virus injection. Abscesses did not develop when streptococci were applied topically to swinepox lesions.


Academic detailing to increase colorectal cancer screening by primary care practices in Appalachian Pennsylvania.
In the United States, colorectal cancer (CRC) is the third most frequently diagnosed cancer and second leading cause of cancer death. Screening is a primary method to prevent CRC, yet screening remains low in the U.S. and particularly in Appalachian Pennsylvania, a largely rural area with high rates of poverty, limited health care access, and increased CRC incidence and mortality rates. Receiving a physician recommendation for CRC screening is a primary predictor for patient adherence with screening guidelines. One strategy to disseminate practice-oriented interventions is academic detailing (AD), a method that transfers knowledge or methods to physicians, nurses or office staff through the visit(s) of a trained educator. The objective of this study was to determine acceptability and feasibility of AD among primary care practices in rural Appalachian Pennsylvania to increase CRC screening. A multi-site, practice-based, intervention study with pre- and 6-month post-intervention review of randomly selected medical records, pre- and post-intervention surveys, as well as a post-intervention key informant interview was conducted. The primary outcome was the proportion of patients current with CRC screening recommendations and having received a CRC screening within the past year. Four practices received three separate AD visits to review four different learning modules. We reviewed 323 records pre-intervention and 301 post-intervention. The prevalence of being current with screening recommendation was 56% in the pre-intervention, and 60% in the post-intervention (p=0.29), while the prevalence of having been screened in the past year increased from 17% to 35% (p<0.001). Colonoscopies were the most frequently performed screening test. Provider knowledge was improved and AD was reported to be an acceptable intervention for CRC performance improvement by the practices. AD appears to be acceptable and feasible for primary care providers in rural Appalachia. A ceiling effect for CRC screening may have been a factor in no change in overall screening rates. While the study was not designed to test the efficacy of AD on CRC screening rates, our evidence suggests that AD is acceptable and may be efficacious in increasing recent CRC screening rates in Appalachian practices which could be tested through a randomized controlled study.


A repetition suppression effect lasting several days within the semantic network.
Performance in a semantic task is speeded up for repeated stimuli compared to novel stimuli. This conceptual priming effect is related to a decrease in functional activation within the left inferior prefrontal cortex for repeated stimulus exposure (repetition suppression). However, in contrast to perceptual priming which is known to be very robust over long periods of time, previous studies on semantic priming focused on short-term effects. The present study combined a behavioral and functional imaging experiment to investigate long-term conceptual repetition priming (retention interval 3 days). We found a highly significant decrease of reaction time for word stimuli which were presented repeatedly after 3 days both compared to initial presentation and to a matched word list. The functional magnetic resonance imaging data showed a repetition suppression within the left inferior (BA45, BA47) and middle (BA9) frontal gyrus for the comparison of known with unknown words. These data demonstrate that even over a period as long as 3 days, a repetition suppression within the left frontal network involved in semantic decision can be found. Thus, priming-related mechanisms in the semantic network may be robust over several days.


White Blood Cell Subtypes Are Associated with a Greater Long-Term Risk of Death after Acute Myocardial Infarction.
We evaluated the association between white blood cell counts and long-term mortality rates in 2,129 patients (mean age, 65.3 ± 13.5 yr; 69% men) who had survived acute myocardial infarction. We obtained white blood cell counts and differential counts of white blood cell subtypes within the first 72 hours of hospital admission. The primary outcome was all-cause death at 1, 5, and 10 years after acute myocardial infarction. In regard to death in the long term, we found significant negative linear associations (lymphocytes), positive linear associations (neutrophils and the neutrophil-to-lymphocyte ratio), and nonlinear U-shaped associations (basophils, eosinophils, monocytes, and total white blood cell count). After multivariate adjustment for the Soroka Acute Myocardial Infarction risk score, lymphocytes (strongest association), neutrophil-to-lymphocyte ratio, and eosinophils were independently associated with death for up to 10 years after hospital discharge. The independent associations weakened over time. We conclude that lymphocyte count, neutrophil-to-lymphocyte ratio, and eosinophil count are independently and incrementally associated with death in the long term after acute myocardial infarction.


Response to the COVID-19 Outbreak in Urban Settings in China.
The COVID-19 outbreak in China was devastating and spread throughout the country before being contained. Stringent physical distancing recommendations and shelter-in-place were first introduced in the hardest-hit provinces, and by March, these recommendations were uniform throughout the country. In the presence of an evolving and deadly pandemic, we sought to investigate the impact of this pandemic on individual well-being and prevention practices among Chinese urban residents. From March 2-11, 2020, 4607 individuals were recruited from 11 provinces with varying numbers of COVID-19 cases using the social networking app WeChat to complete a brief, anonymous, online survey. The analytical sample was restricted to 2551 urban residents. Standardized scales measured generalized anxiety disorder (GAD), the primary outcome. Multiple logistic regression was conducted to identify correlates of GAD alongside assessment of community practices in response to the COVID-19 pandemic. We found that during the COVID-19 pandemic, the recommended public health practices significantly (p < 0.001) increased, including wearing facial mask, practicing physical distancing, handwashing, decreased public spitting, and going outside in urban communities. Overall, 40.3% of participants met screening criteria for GAD and 49.3%, 62.6%, and 55.4% reported that their work, social life, and family life were interrupted by anxious feelings, respectively. Independent correlates of having anxiety symptoms included being a healthcare provider (aOR = 1.58, p < 0.01), living in regions with a higher density of COVID-19 cases (aOR = 2.13, p < 0.01), having completed college (aOR = 1.38, p = 0.03), meeting screening criteria for depression (aOR = 6.03, p < 0.01), and poorer perceived health status (aOR = 1.54, p < 0.01). COVID-19 had a profound impact on the health of urban dwellers throughout China. Not only did they markedly increase their self- and community-protective behaviors, but they also experienced high levels of anxiety associated with a heightened vulnerability like depression, having poor perceived health, and the potential of increased exposure to COVID-19 such as living closer to the epicenter of the pandemic.


Spatio-temporal dynamics of protein kinase B/Akt signaling revealed by a genetically encoded fluorescent reporter.
The serine/threonine kinase protein kinase B (PKB)/Akt is a critical regulator of insulin signaling, cell survival, and oncogenesis. The activation mechanisms of this key kinase are well characterized. In contrast, inactivation of PKB signaling by phosphatases is less well understood. To study the dynamics of PKB signaling in live cells, we generated a genetically encoded fluorescent reporter for PKB activity that reversibly responds to stimuli activating phosphatidylinositol 3-kinase. Specifically, phosphorylation of the reporter expressed in mammalian cells causes changes in fluorescence resonance energy transfer, allowing real-time imaging of phosphorylation catalyzed by PKB. Because of its reversibility, the reporter also allows termination of PKB signaling by phosphatases to be monitored. We found that PKB signaling in the cytosol was more rapid and more transient compared with that in the nucleus, suggesting the presence of differentially regulated phosphatase activity in these two compartments. Furthermore, targeting of the reporter to the plasma membrane, where PKB is activated, resulted in accelerated and prolonged response compared with the response in the cytosol, suggesting that release of PKB or its substrates from the membrane is required for desensitization of PKB signaling. These data reveal spatio-temporal gradients of both signal propagation and signal termination in PKB signaling.


Serum creatinine is a poor marker of glomerular filtration rate in patients with spina bifida.
Serum creatinine is used to estimate the glomerular filtration rate (GFR). The serum creatinine, however, may not accurately reflect the GFR in spina bifida patients, who often have decreased overall muscle mass resulting from spinal cord abnormalities. The relationship between the serum creatinine and GFR (obtained by [(125)I]iothalamate clearance) was examined in a population of spina bifida patients. Age-matched patients without spina bifida were used as controls. Results demonstrate that, for serum creatinines above 0.5 mg/dL, serum creatinine is a very poor predictor of GFR. Two patients with serum creatinines of 2.2 mg/dL are near end-stage renal disease with GFRs of 12.5 and 13 mL/minute per 1.73m2 and two patients were initiated on dialysis at the conclusion of the study. It is concluded that obtaining a GFR from a clearance study and not serum creatinine is the only reliable method to assess renal function in spina bifida patients once the serum creatinine is greater than 0.5 mg/dL.


Brain oxytocin: a key regulator of emotional and social behaviours in both females and males.
In addition to various reproductive stimuli, the neuropeptide oxytocin (OXT) is released both from the neurohypophysial terminal into the blood stream and within distinct brain regions in response to stressful or social stimuli. Brain OXT receptor-mediated actions were shown to be significantly involved in the regulation of a variety of behaviours. Here, complementary methodological approaches are discussed which were utilised to reveal, for example, anxiolytic and anti-stress effects of OXT, both in females and in males, effects that were localised within the central amygdala and the hypothalamic paraventricular nucleus. Also, in male rats, activation of the brain OXT system is essential for the regulation of sexual behaviour, and increased OXT system activity during mating is directly linked to an attenuated anxiety-related behaviour. Moreover, in late pregnancy and during lactation, central OXT is involved in the establishment and fine-tuned maintenance of maternal care and maternal aggression. In monogamous prairie voles, brain OXT is important for mating-induced pair bonding, especially in females. Another example of behavioural actions of intracerebral OXT is the promotion of social memory processes and recognition of con-specifics, as revealed in rats, mice, sheep and voles. Experimental evidence suggests that, in humans, brain OXT exerts similar behavioural effects. Thus, the brain OXT system seems to be a potential target for the development of therapeutics to treat anxiety- and depression-related diseases or abnormal social behaviours including autism.


Experiences of Tourette Syndrome Caregivers With Supportive Communication.
The experiences of Tourette syndrome (TS) caregivers with supportive communication are examined in this qualitative investigation. TS is a childhood-onset neurodevelopmental disorder marked by a combination of involuntary verbal and motor tics lasting for more than 1 year. Although individuals are impacted the most by TS, the stress for caring for a child with TS takes an emotional and physical toll on the caregiver. Eleven participants shared their experiences with receiving supportive communication by taking part in semi-structured interviews. Data analysis yielded three themes: (a) TS caregivers describe their experiences as a struggle; (b) they seek out specific social support from friends and families; and (c) they frequently receive social support that increases instead of reducing stress.


The core histone N-terminal tail domains function independently and additively during salt-dependent oligomerization of nucleosomal arrays.
Salt-dependent oligomerization of nucleosomal arrays is related to fiber-fiber interactions and global chromosome structure. Previous studies have shown that the H2A/H2B and H3/H4 N-terminal domain (NTD) pairs are able to mediate array oligomerization. However, because of technical barriers, the function(s) of the individual core histone NTDs have not been investigated. To address this question, all possible combinations of "tailless" nucleosomal arrays were assembled from native and NTD-deleted recombinant Xenopus core histones and tandemly repeated 5 S rDNA. The recombinant arrays were characterized by differential centrifugation over the range of 0-50 mm MgCl2 to determine how each NTD affects salt-dependent oligomerization. Results indicate that all core histone NTDs participate in the oligomerization process and that the NTDs function additively and independently. These observations provide direct biochemical evidence linking all four core histone NTDs to the assembly and maintenance of global chromatin structures.


A Case of Varicella Combined with Hand-foot-mouth Disease in a Healthy Child.
We report here on an 11-year-old child with a pustulovesicular eruption on her whole body, including her palms, soles and oral mucosa, and this was accompanied with fever. A serologic test was positive for IgM varicella zoster antibody and coxsackievirus A16 antibody. The histopathologic examination from the palm revealed intraepidermal pustules that showed neither inclusion bodies nor multinucleated giant cells. We made the final diagnosis, according to the serologic tests and histopathologic findings, as varicella combined with hand-foot-mouth disease caused by coxsackievirus A16 in a previously healthy child.


Measuring local conformations and conformational disorder of (Cy3)2 dimer labeled DNA fork junctions using absorbance, circular dichroism and two-dimensional fluorescence spectroscopy.
The sugar-phosphate backbone of DNA near single-stranded (ss)-double-stranded (ds) junctions likely fluctuates within a broad distribution of conformations to permit the proper binding of genome regulatory proteins that function at these sites. In this work we use absorbance, circular dichroism (CD), and two-dimensional fluorescence spectroscopy (2DFS) to study the local conformations and conformational disorder within chromophore-labeled DNA constructs. These constructs employ dimers of the fluorescent chromophore Cy3 that are site-specifically incorporated into the sugar-phosphate backbones of DNA strands at ss-ds DNA fork junctions. We show that these data can be analyzed to determine the local conformations of the (Cy3)2 dimer, and the degree of conformational disorder. Our analysis employs an essential-state Holstein-Frenkel Hamiltonian model, which takes into account the internal electronic-vibrational motions within each Cy3 chromophore, and the resonant electronic interaction that couples the two chromophores together. Our results suggest that this approach may be applied generally to understand local backbone conformation and conformational disorder at ss-ds DNA fork junctions.


Rheumatoid arthritis: an overview of new and emerging therapies.
Rheumatoid arthritis (RA) is a chronic, inflammatory, systemic autoimmune disorder characterized by symmetric inflammation of synovial joints leading to progressive erosion of cartilage and bone. The aim of treatment is to mitigate joint destruction, preserve function, and prevent disability. The American College of Rheumatology guidelines for the treatment of RA recommend that newly diagnosed patients with RA begin treatment with disease-modifying antirheumatic drugs (DMARDs) within 3 months of diagnosis. Methotrexate remains the most commonly prescribed DMARD and is the standard by which recent new and emerging therapies are measured. Increasing knowledge regarding the immunologic basis of RA and advances in biotechnology have resulted in new, targeted biological therapies against proinflammatory cytokines that have dramatically changed the treatment paradigm and outcomes of patients with RA. This article reviews the pharmacological rationale underlying RA therapy, with a focus on currently available biological therapies and new therapies in development.


Polymorphisms past and present.
Polymorphisms, particularly genetic variants of the red blood cell, have served as a major focus for the research of Frank B. Livingstone over the course of a long and productive career. Recent investigations confirm the value of key insights that he contributed to this area more than four decades ago. As Livingstone recognized, the same underlying evolutionary model that guides genetic studies in present populations also provides a productive framework for interpreting patterns of variation in the skeleton and dentition throughout past human evolution. Examples explored in detail here include polymorphisms in hominoid nasal bone shapes and fourth lower premolar roots. This work provides both empirical and theoretical contexts for investigating patterns of human variation over the last 6 to 8 million years.


Methods to analyze bone regenerative response to different rhBMP-2 doses in rabbit craniofacial defects.
Multiple assessment methods are available to evaluate the performance of engineered scaffolds in accepted bone healing animal models. Evaluation and comparison of these methods can aid in the planning of future animal studies, as well as, inform clinical assessments as the engineered scaffolds translate into clinical studies and applications. To evaluate multiple bone assessment techniques, bone regrowth potential of tyrosine-derived polycarbonate (TyrPC) scaffolds loaded with various dosages of recombinant human bone morphogenetic protein-2 (rhBMP-2) (0, 10, 25, and 50 μg) was assessed after 16 weeks in vivo in a rabbit calvarial model. Traditional X-ray radiography and micro-computed tomography (micro-CT) analyses were used to quantify the volume and density of regenerated bone. Histomorphometric analysis was performed as the traditional gold standard of evaluation. While these techniques are fairly standard in bone tissue engineering, we also investigated 64-slice CT, a tool more commonly used clinically, for comparison and to guide translational efforts. The 64-slice CT scans were carried out at 4 and 16 weeks to monitor temporal bone healing patterns. Study results indicated a clear dose-dependent response of increasing regenerated bone volume with rhBMP-2 loaded on the TyrPC scaffolds after 16 weeks of implantation. Significantly more bone formation was observed at the highest dose of rhBMP-2 (50 μg), which is 25-50% of the previously recommended dose (100-200 μg) for this defect. A significant difference was observed between the lowest and highest doses using radiographs (p<0.001), micro-CT (p=0.002), and CT (p<0.001) and a high correlation was found between techniques (R(2) values between 0.446 and 0.911). It was found that the number of animals required per group to detect significant dose effects ranged between 6 and 8 for the imaging methods while histomorphometric analysis would require 25 animals per group to detect similar differences (desired power=0.9, α=0.05). Radiographic analysis provided quantifiable % defect coverage and radio-opacity, micro-CT provided spatial volumetric and bone density measures, histomorphometry provided biological confirmation, and 64-slice CT allowed for establishing of clinically relevant translational guidelines. These methodologies allow for a standardized and comprehensive description of bone regeneration and provide guidelines for the planning of future preclinical and clinical studies.


Analysis of the Factors That Could Predict Segmental Range of Motion After Cervical Artificial Disk Replacement: A 7-Year Follow-up Study.
A retrospective cohort study. To identify the potential preoperative factors and surgical technique factors that are associated with long-term range of motion (ROM) after surgery. Further, this article aimed to guide selection of patients with cervical artificial disk replacement and a fine surgical technique. Segmental ROM is the most important parameter concerning cervical kinematics after a cervical artificial disk replacement. There are few researches regarding the influencing factors on postoperative ROM, and consistent results have not yet been reported. The cohort comprised a total of 68 disks implanted into 57 patients who were retrospectively analyzed. The mean follow-up period was 84.1 months. Segmental ROM and other useful parameters were measured using lateral neutral, extension, and flexion radiographs, which were obtained preoperatively, 3 months after surgery, and at last follow-up. Preoperative CT and clinical assessment were also used. To find out associated factors, the patients were divided into 2 groups according to the segmental ROM at last follow-up. After surgery, the clinical outcomes were satisfactory. The segmental ROM at last follow-up (7.8±4.3 degrees) was preserved without significant change from preoperative ROM (8.8±3.8 degrees). The patients who had a better segmental ROM after surgery were found to have a higher preoperative segmental ROM, a younger age, a better disk insertion angle, and disk insertion depth. These 4 factors were identified as independent risk factors (P=0.027, 0.017, 0.036, and 0.046, respectively) for long-term ROM. The postoperative long-term, segmental ROM was well preserved and found to be affected by the preoperative segmental ROM, patient's age, disk insertion angle, and disk insertion depth.