Prospective, Multicenter, Randomized, Crossover Clinical Trial Comparing the Safety and Effectiveness of Cooled Radiofrequency Ablation With Corticosteroid Injection in the Management of Knee Pain From Osteoarthritis.
Osteoarthritis (OA) of the knee affects the aging population and has an associated influence on the health care system. Rigorous studies evaluating radiofrequency ablation for OA-related knee pain are lacking. This study compared long-term clinical safety and effectiveness of cooled radiofrequency ablation (CRFA) with intra-articular steroid (IAS) injection in managing OA-related knee pain. This is a prospective, multicenter, randomized trial with 151 subjects with chronic (≥6 months) knee pain that was unresponsive to conservative modalities. Knee pain (Numeric Rating Scale [NRS]), Oxford Knee Score, overall treatment effect (Global Perceived Effect), analgesic drug use, and adverse events were compared between CRFA and IAS cohorts at 1, 3, and 6 months after intervention. There were no differences in demographics between study groups. At 6 months, the CRFA group had more favorable outcomes in NRS: pain reduction 50% or greater: 74.1% versus 16.2%, P < 0.0001 (25.9% and 83.8% of these study cohorts, respectively, were nonresponders). Mean NRS score reduction was 4.9 ± 2.4 versus 1.3 ± 2.2, P < 0.0001; mean Oxford Knee Score was 35.7 ± 8.8 vs 22.4 ± 8.5, P < 0.0001; mean improved Global Perceived Effect was 91.4% vs 23.9%, P < 0.0001; and mean change in nonopioid medication use was CRFA > IAS (P = 0.02). There were no procedure-related serious adverse events. This study demonstrates that CRFA is an effective long-term therapeutic option for managing pain and improving physical function and quality of life for patients with painful knee OA when compared with IAS injection. ClinicalTrials.gov (NCT02343003).


[Evaluation of remicade efficiency for the treatment of rheumatoid arthritis].
The treatment of patients with severe rheumatoid arthritis (RA), who have resistance to basic anti-inflammatory medications (BAIM) has not been always effective. Moreover, a prolonged use of BAIM can cause side effects. Nowadays, REMICADE biological preparation has been used in practical activity by rheumatologists as an inhibitor TNF-alpha. The use of Remicade during 52 weeks gives positive results and improves existence quality of patients with RA.


Transluminal Pillars-Their Origin and Role in the Remodelling of the Zebrafish Caudal Vein Plexus.
Intussusceptive pillars, regarded as a hallmark of intussusceptive angiogenesis, have been described in developing vasculature of many organs and organisms. The aim of this study was to resolve the question about pillar formation and their further maturation employing zebrafish caudal vein plexus (CVP). The CVP development was monitored by in vivo confocal microscopy in high spatio-temporal resolution using the transgenic zebrafish model Fli1a:eGPF//Gata1:dsRed. We tracked back the formation of pillars (diameter ≤ 4 µm) and intercapillary meshes (diameter > 4 µm) and analysed their morphology and behaviour. Transluminal pillars in the CVP arose via a combination of sprouting, lumen expansion, and/or the creation of intraluminal folds, and those mechanisms were not associated directly with blood flow. The follow-up of pillars indicated that one-third of them disappeared between 28 and 48 h post fertilisation (hpf), and of the remaining ones, only 1/17 changed their cross-section area by >50%. The majority of the bigger meshes (39/62) increased their cross-section area by >50%. Plexus simplification and the establishment of hierarchy were dominated by the dynamics of intercapillary meshes, which formed mainly via sprouting angiogenesis. These meshes were observed to grow, reshape, and merge with each other. Our observations suggested an alternative view on intussusceptive angiogenesis in the CVP.


The Anti-Breast Cancer Stem Cell Potency of Copper(I)-Non-Steroidal Anti-Inflammatory Drug Complexes.
Cancer stem cells (CSCs) are thought to be partly responsible for metastasis and cancer relapse. Currently, there are no effective therapeutic options that can remove CSCs at clinically safe doses. Here, we report the synthesis, characterisation, and anti-breast CSC properties of a series of copper(I) complexes, comprising of non-steroidal anti-inflammatory drugs (NSAIDs) and triphenylphosphine ligands (1-3). The copper(I) complexes are able to reduce the viability of breast CSCs grown in two- and three-dimensional cultures at micromolar concentrations. The potency of the copper(I) complexes towards breast CSCs was similar to salinomycin (an established anti-breast CSC agent) and cisplatin (a clinically used metallopharmaceutical). Cell-based studies showed that the copper(I) complexes are readily, and similarly, internalised by breast CSCs. The copper(I) complexes significantly increase the intracellular reactive oxygen species (ROS) levels in breast CSCs, and their ROS generation profile with respect to time is dependent on the NSAID component present. The generation of intracellular ROS by the copper(I) complexes could be part of the underlying mechanism by which they evoke breast CSC death. As far as we are aware, this is the first study to explore the anti-breast CSC properties of copper(I) complexes.


No socioeconomic inequalities in ovarian cancer survival within two randomised clinical trials.
Ovarian cancer is the leading cause of death among cancers of the female genital tract, with poor outcomes despite chemotherapy. There was a persistent socioeconomic gradient in 1-year survival in England and Wales for more than 3 decades (1971-2001). Inequalities in 5-year survival persisted for more than 20 years but have been smaller for women diagnosed around 2000. We explored one possible explanation. We analysed data on 1406 women diagnosed with ovarian cancer during 1991-1998 and recruited to one of two randomised clinical trials. In the second International Collaborative Ovarian Neoplasm (ICON2) trial, women diagnosed between 1991 and 1996 were randomised to receive either the three-drug combination cyclophosphamide, doxorubicin and cisplatin (CAP) or single-agent carboplatin given at optimal dose. In the ICON3 trial, women diagnosed during 1995-1998 were randomised to receive either the same treatments as ICON2, or paclitaxel plus carboplatin.Relative survival at 1, 5 and 10 years was estimated for women in five categories of socioeconomic deprivation. The excess hazard of death over and above background mortality was estimated by fitting multivariable regression models with Poisson error structure and a dedicated link function in a generalised linear model framework, adjusting for the duration of follow-up and the confounding effects of age, Federation of Gynecology and Obstetrics (FIGO) stage and calendar period. Unlike women with ovarian cancer in the general population, no statistically significant socioeconomic gradient was seen for women with ovarian cancer treated in the two randomised controlled trials. The deprivation gap in 1-year relative survival in the general population was statistically significant at -6.7% (95% CI (-8.1, -5.3)), compared with -3.6% (95% CI (-10.4, +3.2)) in the trial population. Although ovarian cancer survival is significantly lower among poor women than rich women in England and Wales, there was no evidence of an association between socioeconomic deprivation and survival among women with ovarian cancer who were treated and followed up consistently in two well-conducted randomised controlled trials. We conclude that the persistent socioeconomic gradient in survival among women with ovarian cancer, at least for 1-year survival, may be due to differences in access to treatment and standards of care.


An integrative multi-dimensional genetic and epigenetic strategy to identify aberrant genes and pathways in cancer.
Genomics has substantially changed our approach to cancer research. Gene expression profiling, for example, has been utilized to delineate subtypes of cancer, and facilitated derivation of predictive and prognostic signatures. The emergence of technologies for the high resolution and genome-wide description of genetic and epigenetic features has enabled the identification of a multitude of causal DNA events in tumors. This has afforded the potential for large scale integration of genome and transcriptome data generated from a variety of technology platforms to acquire a better understanding of cancer. Here we show how multi-dimensional genomics data analysis would enable the deciphering of mechanisms that disrupt regulatory/signaling cascades and downstream effects. Since not all gene expression changes observed in a tumor are causal to cancer development, we demonstrate an approach based on multiple concerted disruption (MCD) analysis of genes that facilitates the rational deduction of aberrant genes and pathways, which otherwise would be overlooked in single genomic dimension investigations. Notably, this is the first comprehensive study of breast cancer cells by parallel integrative genome wide analyses of DNA copy number, LOH, and DNA methylation status to interpret changes in gene expression pattern. Our findings demonstrate the power of a multi-dimensional approach to elucidate events which would escape conventional single dimensional analysis and as such, reduce the cohort sample size for cancer gene discovery.


The cII locus in the MutaMouse system.
Here, we report the first application and characterization of the cII locus as a mutational target for use with the Muta(trade mark)Mouse system for quantifying somatic mutations in vivo. This locus can be analyzed for mutations using positive selection and is identical in sequence to the cII in the Big Blue((R)) Mouse. The cII displays similar spontaneous (5.5 x 10(-5)) and induced mutation frequencies when compared to the lacZ gene in the small intestine of MutaMice treated with ENU (N-ethyl-N-nitrosourea). After acute treatment with 250 mg/kg ENU (ip) the mutant frequencies were 127 x 10(-5) at the cII and 147 x 10(-5) at the lacZ loci, reaching a maximal mutant frequency 10 days posttreatment and remaining constant thereafter. These data prove that this transgene is genetically neutral, conferring neither selective advantage nor disadvantage on the host cells. The cII dose response curve was linear (R(2) = 0.93) comparable to the lacZ after treatments with 0, 50, 150, or 250 mg/kg ENU. Use of the cII locus (0.3 kb) addresses the single most significant drawback associated with the MutaMouse system, namely the inability to obtain sequence spectra efficiently, due to the large size of the lacZ gene (3.0 kb). Moreover, a less obvious application, but nevertheless of considerable importance, is the easy identification of jackpot mutations, without sequencing. The cII, identical in both sequence and origin on the transgenic constructs used in producing the Big Blue and MutaMouse systems, provides the first transgenic locus common to the two widely used in vivo mutagenesis assays.


Early Recognition of Behaviour Problems in Shelter Dogs by Monitoring them in their Kennels after Admission to a Shelter.
Canine behaviour assessments are commonly used in shelters to identify behaviour problems in dogs prior to adoption. The aim of this study was to evaluate whether kennel monitoring of dogs could identify early signs of behaviour problems, thereby facilitating early intervention and better management of dogs displaying behaviour problems. Kennel behaviour was monitored for dogs (n = 38) in their first five days in kennels at a shelter in Brisbane, Australia. This was compared to a formal assessment of exploratory, handling, play, run/freeze, and food guarding behaviour, as well as stranger and fake toddler interactions, and behaviour when the dog was alone, conducted five days after shelter admission. Kennel behaviours associated with fear, anxiety, and arousal in dogs were significantly correlated with the same behaviours in the formal assessment. Positional correlations were also evident. With respect to outcomes, dogs that displayed more whining, tense body posture, standing leaning forward, panting, ears forward, less barking, lowered body and balanced/relaxed body posture, standing still, and standing by the wall had increased odds of failing the behaviour assessment. Over the five days in the kennel, the frequency and duration of fear-related behaviours decreased, suggesting a reduction in arousal as the dog became accustomed to the shelter environment. The study demonstrates that monitoring kennel behaviour could detect early signs of behaviour problems.


The araIc mutation in Escherichia coli B/r.
The araIc allele is a cis-acting mutation which has been used to define the araBAD promoter in Escherichia coli B/r. Nineteen araIc mutants were originally isolated by Englesberg and co-workers as Ara+ "revertants" of an araC deletion mutant (Englesberg et al. J. Mol. Biol. 43:281-298, 1969). The mutants constitutively expressed araBAD gene products in the absence of functional araC activator protein. Eight of the araIc mutations have been cloned by in vivo recombination onto pBR322-ara hybrid plasmids. Restriction and DNA sequence analysis of these araIc mutations showed that they result from a single base-pair change located at -35 in the araBAD promoter.


[Effectiveness and safety of the treatment with sildenafil (Viagra) in patients with erectile dysfunction and arterial hypertension].
To evaluate the efficacy and safety of sildenafil in the treatment of erectile dysfunction in hypertensive patients taking antihypertensive drugs, and to investigate factors associated to treatment failure. Observational prospective study comparing two groups of patients suffering from erectile dysfunction with or without hypertension. Patients were evaluated by anamnesis, physical examination, blood tests, and the International Index of Erectile Function (IIEF). Blood pressure was measured before and after treatment with an automatic digital oscillometric device. Erections improved in 88.2% and 91.7% of the patients with an without hypertension respectively. On the initial visit 55.2% of all patients had severe dysfunction, which was reduced after sildenafil treatment to 4.7%. Diastolic arterial blood pressure, evaluated in random measures, was slightly reduced after starting treatment with Viagra. No significant adverse events were registered. Oral treatment with sildenafil in patients with erectile dysfunction and hypertension is effective, well-tolerated and does not produce pharmacologic interactions with antihypertensive drugs.


Accuracy and reproducibility of the AutoMicrobic System Gram-Negative General Susceptibility-Plus Card for testing selected challenge organisms.
A total of 180 selected strains of gram-negative bacilli were tested for susceptibility to nine antibiotics by the prototype General Susceptibility Card and reference broth microdilution MIC method, and 112 of 180 were tested by the modified Gram-Negative General Susceptibility-Plus Card (Vitek Systems, Inc., Hazelwood, Mo.). When category calls--susceptible, intermediate, and resistant for the prototype card and very susceptible, moderately susceptible, and resistant for the modified card--were identical or compatible (very susceptible by one method and moderately susceptible by the other), the methods were considered in qualitative or categorical agreement. The overall categorical agreement improved from 83% for the prototype card to 91.5% for the modified card, and the frequency of major and very major disagreements was reduced from 7.5 to 1%, respectively. Overall agreement between the modified card and reference method for both category calls and MICs (+/- 2 dilutions) was 90%. Of the results, 67% were identical, 22% were more susceptible with the modified card, and 11% were more resistant. Reproducibility of identical or compatible category calls and MICs obtained from three trials was 94.5%. The poorest accuracy and reproducibility were observed when testing Pseudomonas aeruginosa. The study suggests that the modified card can rapidly and efficiently perform susceptibility tests with an acceptable level of accuracy and reproducibility provided that the system is appropriately used for testing strains of the family Enterobacteriaceae with preset criteria for excluding organism-antibiotic combinations. The evaluation also indicates dramatic improvement in the technical performance of the modified card compared with its earlier prototype.


Effects of divalent cations, lanthanum, cation chelators and an ionophore on acetylcholine antinociception.
The antinociceptive effect of intracerebroventricularly administered acetylcholine as measured in the mouse tail-flick test was reduced by intracerebroventricularly injected calcium, magnesium and manganese. Maximum antagonism of acetylcholine-induced antinociception was observed with a 1-hour calcium pretreatment. Significant reduction existed at 2- but not 4-hour pretreatment. Barium and strontium were inactive. The antinociceptive effect of acetylcholine was potentiated by lanthanum and ethylene glycol tetraacetic acid but not by ethylenediamine tetraacetic acid. The ionophore A23187 was shown to increase greatly the antagonistic effect of a low dose of calcium. The ionophore alone did not significantly alter the effect of acetylcholine. Thus, it appears that calcium must penetrate cell membranes to reduce the effect of acetylcholine. In addition to acetylcholine, it was found that the antinociceptive effects of oxotremorine and physostigmine could also be reduced by calcium. These data indicate that alterations in intracellular calcium are involved in cholinergically induced antinociception.


Concentration and detection of caliciviruses from food contact surfaces.
Outbreaks of human Norwalk virus (NV) and Norwalk-like viruses often originate in food service establishments. No reliable method is available for the detection of these human caliciviruses on food contact surfaces. We describe a simple method for the detection of NV from stainless steel work surfaces using cultivable feline calicivirus (FCV) as a model. Stainless steel surfaces were artificially contaminated with known amounts of FCV, followed by its elution in a buffer solution. Three methods of virus elution were compared. In the first method, moistened cotton swabs or pieces of nylon filter (1MDS) were used to elute the contaminating virus. The second method consisted of flooding the contaminated surface with eluting buffer, allowing it to stay in contact for 15 min, followed by aspiration of the buffer (aspiration method) after a contact period of 15 min. The third method, the scraping-aspiration method, was similar to the aspiration method, except that the surfaces were scraped with a cell scraper before buffer aspiration. Maximum virus recovery (32 to 71%) was obtained with the scraping-aspiration method using 0.05 M glycine buffer at pH 6.5. Two methods (organic flocculation and filter adsorption elution) were compared to reduce the volume of the eluate recovered from larger surfaces. The organic flocculation method gave an average overall recovery of 55% compared to the filter-adsorption-elution method, which yielded an average recovery of only 8%. The newly developed method was validated for the detection of NV by artificial contamination of 929-cm2 stainless steel sheets with NV-positive stool samples and for the detection of the recovered virus by reverse transcription-polymerase chain reaction.


Loss of Elongation-Like Factor 1 Spontaneously Induces Diverse, RNase H-Related Suppressor Mutations in Schizosaccharomyces pombe.
A healthy individual may carry a detrimental genetic trait that is masked by another genetic mutation. Such suppressive genetic interactions, in which a mutant allele either partially or completely restores the fitness defect of a particular mutant, tend to occur between genes that have a confined functional connection. Here we investigate a self-recovery phenotype in Schizosaccharomyces pombe, mediated by suppressive genetic interactions that can be amplified during cell culture. Cells without Elf1, an AAA+ family ATPase, have severe growth defects initially, but quickly recover growth rates near to those of wild-type strains by acquiring suppressor mutations. elf1Δ cells accumulate RNAs within the nucleus and display effects of genome instability such as sensitivity to DNA damage, increased incidence of lagging chromosomes, and mini-chromosome loss. Notably, the rate of phenotypic recovery was further enhanced in elf1Δ cells when RNase H activities were abolished and significantly reduced upon overexpression of RNase H1, suggesting that loss of Elf1-related genome instability can be resolved by RNase H activities, likely through eliminating the potentially mutagenic DNA-RNA hybrids caused by RNA nuclear accumulation. Using whole genome sequencing, we mapped a few consistent suppressors of elf1Δ including mutated Cue2, Rpl2702, and SPBPJ4664.02, suggesting previously unknown functional connections between Elf1 and these proteins. Our findings describe a mechanism by which cells bearing mutations that cause fitness defects and genome instability may accelerate the fitness recovery of their population through quickly acquiring suppressors. We propose that this mechanism may be universally applicable to all microorganisms in large-population cultures.


Needs Assessment Lessons Learned in Qatar: A Flipped Classroom Approach.
This article was migrated. The article was marked as recommended. Continuing professional development (CPD) activities are expected to be purposeful and effective; the essential first step is a curriculum based on actual training needs. The Qatar Council for Healthcare Practitioners (QCHP) provides the oversight for accredited CPD programs for all groups of healthcare practitioners in Qatar this includes physicians, pharmacists, nurses and allied health professionals. In December 2017 several professionals created a local, collaborative and supportive network to share their expertise and to collaborate on accredited professional development initiatives. Network members included accredited CPD providers from two hospitals, Sidra Medicine and Aspetar, and from the College of the North Atlantic Qatar (CNA-Q). The implementation of a needs analysis is key to continuous service improvements. Network members conducted an audit of 43 educational programs in 2018 and found that this step is frequently missed or misinterpreted by curriculum planners. A workshop on needs assessments was seen as the most germane intervention to upskill program planners. An evidence-based approach was suggested in the development of a needs assessment teaching module. A review of the literature influenced the curriculum design as did a re-examination of adult learning principles and validated new methods to teaching in the health professions. The flipped classroom was identified as the most appropriate approach regarding design and content delivery. It requires skilled facilitators and content matter experts that are familiar with diverse teaching formats to ensure that learning outcomes are integrated across the formats. It has been documented that 'flipping' the classroom from a teacher-centered to a learner-centered approach encourages participants' higher order learning and fosters engagement, exploration, evaluation and reflection.


Ageing and neurotrophic signalling effects on diaphragm neuromuscular function.
The age-related mechanisms underlying sarcopenia are largely unknown. We hypothesize that age-related neuromuscular changes depend on brain-derived neurotrophic factor (BDNF) acting through the tropomyosin-related kinase receptor B (TrkB). Maximal specific force and neuromuscular transmission failure were assessed at 6, 18 and 24 months following control, BDNF or phosphoprotein phosphatase 1 derivative (1NMPP1) treatment in male TrkB(F616A) mice. Phosphoprotein phosphatase-1 derivatives such as 1NMPP1 inhibit TrkB kinase activity as a result of this single amino acid mutation in the ATP binding domain. Maximal twitch and isometric tetanic force were reduced at 24 months compared to 6 and 18 months (P < 0.001). Neuromuscular transmission failure significantly increased at 18 and 24 months compared to 6 months (age × treatment interaction: P < 0.001). Neuromuscular transmission was improved following BDNF at 6 and 18 months and was impaired only at 6 months following 1NMPP1 treatment. Age and inhibition of TrkB kinase activity had similar effects on neuromuscular transmission failure, supporting a critical role for BDNF/TrkB signalling on neuromuscular changes in ageing. These results suggest that an age-related loss of endogenous BDNF precedes reductions in TrkB kinase activity in the diaphragm muscle.


4,8-Dicarboxyl-8,9-iridoid-1-glycoside inhibits apoptosis in human osteoarthritis chondrocytes via enhanced c-MYC-mediated cholesterol metabolism in vitro.
Osteoarthritis (OA) is a degenerative disease related to cholesterol metabolism disorders. However, current therapies for OA are insufficient and no convincing disease-modifying OA drugs exist. Therefore, we aimed to elucidate the mechanism by which borojoa iridoid glycoside (BIG) inhibits chondrocyte apoptosis in OA. Borojoa pulp was heated to 70 °C, and the main active substance in borojoa, BIG, was extracted by fractionation at an ultraviolet 254-nm absorption peak. Chondrocytes were identified by immunohistochemistry and visualized by immunofluorescence confocal microscopy. The proliferation of chondrocytes cultured with BIG was determined by MTS assay. The apoptosis of chondrocytes cultured with BIG was tested by Annexin V-FITC/PI, and the cytokine, protein, and cholesterol levels in chondrocytes were detected by ELISA, RT‒qPCR, Western blot, and biochemistry analyses. Protein‒protein interactions were verified by a coimmunoprecipitation (Co-IP) assay. BIG promoted chondrocyte proliferation and reduced apoptosis in vitro. BIG induced an alteration of the total RNA profiles in chondrocytes, and bioinformatic analysis showed that BIG inhibited chondrocyte apoptosis by promoting c-MYC expression; KEGG analysis confirmed that BIG-inhibited apoptosis was enriched in the cell cycle pathway. Flow cell cycle experiments confirmed that BIG promoted chondrocyte proliferation by significantly increasing the S phase cell number. The c-MYC inhibitor 10058-F4 stimulated the increased expression of IL-1β, IL-6, TNF-α, and AGEs and suppressed the cholesterol metabolism, which promoted chondrocyte apoptosis and autophagy. Co-IP analysis showed that BIG promoted the interaction of c-MYC and CH25H, Bcl-2, which suggests that BIG could inhibit chondrocyte apoptosis in part by enhancing c-MYC-mediated cholesterol metabolism. This study confirmed that BIG promotes chondrocyte proliferation and inhibits apoptosis and autophagy, and BIG improving OA is associated with cholesterol metabolism. The results identify a potential mechanism by which BIG enhances c-MYC-mediated CH25H regulation of cholesterol metabolism in vitro and suggest that BIG might be a promising new drug against OA.


Mesencephalic clefts with associated eye movement disorders.
To describe two patients with mesencephalic midline clefts and associated eye movement disorders. Case reports. The first patient developed bilateral internuclear ophthalmoplegia with exotropia, reduced convergence, right ptosis, right fourth-nerve palsy, and right elevator palsy several years after meningitis with hydrocephalus. The second patient had bilateral internuclear ophthalmoplegia with exotropia, reduced convergence, bilateral ptosis, limited upward gaze, and right hypertropia since childhood. In both patients, magnetic resonance imaging showed a midline cleft extending from the cerebral aqueduct into the midbrain. It is likely that the clefts affected the oculomotor nuclei and medial longitudinal fasciculi, accounting for the eye movement disorders.


Culture and Food Practices of African American Women With Type 2 Diabetes.
Purpose The goals of this descriptive ethnographic study were to (1) describe the day-to-day selection, preparation, and consumption of food among African American women (AAW) with type 2 diabetes mellitus (T2DM); (2) identify their typical food selections and consumption practices when dining out at restaurants and at social gatherings (ie, church functions, holidays); (3) highlight the valued behaviors and beliefs that influence these women's food practices; and (4) determine how social interactions influence those food practices. Methods Symbolic interactionism, a sensitizing framework, guided this study. Purposeful sampling was used to recruit 20 AAW from 35 to 70 years of age diagnosed with T2DM who shopped and prepared meals for their families and attended church functions where food was served. Data collection consisted of one-on-one interviews and observations of participants during church fellowship dinners, grocery shopping, and food preparation. A social anthropological approach to content analysis was used to describe behavioral regularities in food practices. Results Informants exhibited a constant struggle in food practices, particularly within the home setting. Difficulties in making dietary modifications resulted from conflicts between the need to change dietary practices to control diabetes and personal food preferences, food preferences of family members, and AAW's emotional dedication to the symbolism of food derived from traditional cultural food practices passed down from generation to generation. Conclusions African American women are the gatekeepers for family food practices, holding the keys to healthy dietary practices. This study helps to fill the research gap regarding cultural dietary food practices within this population.


CNK and HYP form a discrete dimer by their SAM domains to mediate RAF kinase signaling.
RAF kinase functions in the mitogen-activated protein kinase (MAPK) pathway to transmit growth signals to the downstream kinases MEK and ERK. Activation of RAF catalytic activity is facilitated by a regulatory complex comprising the proteins CNK (Connector enhancer of KSR), HYP (Hyphen), and KSR (Kinase Suppressor of Ras). The sterile alpha-motif (SAM) domain found in both CNK and HYP plays an essential role in complex formation. Here, we have determined the x-ray crystal structure of the SAM domain of CNK in complex with the SAM domain of HYP. The structure reveals a single-junction SAM domain dimer of 1:1 stoichiometry in which the binding mode is a variation of polymeric SAM domain interactions. Through in vitro and in vivo mutational analyses, we show that the specific mode of dimerization revealed by the crystal structure is essential for RAF signaling and facilitates the recruitment of KSR to form the CNK/HYP/KSR regulatory complex. We present two docking-site models to account for how SAM domain dimerization might influence the formation of a higher-order CNK/HYP/KSR complex.


Non-communicable diseases and the social determinants of health in the Nordic countries: Findings from the European Social Survey (2014) special module on the social determinants of health.
Comparative studies examining non-communicable diseases (NCDs) and determinants of health in the Nordic countries are scarce, outdated and focus only on a limited range of NCDs and health determinants. This study is the first to present a comprehensive overview of the distribution of social and behavioural determinants of health and of physical and mental NCDs in the Nordic population. We examined regional, country and gender differences for 17 health outcomes and 20 determinants of health. We use data from the 7th wave of the European Social Survey. All results were age-standardised by weighting up or down the unstandardized (crude) prevalence rates for five year age groups in each country to a common standard. We present pooled estimates for the combined regional samples as well as country-specific results for the Nordic region. Overall, the population of the Nordic region reported among the highest prevalence for one or both genders in 10 out of 17 health outcomes. Despite being the region with the highest prevalence for most health outcomes, overall self-rated health levels tend to be better in the Nordic region. Similarly, we found that the Nordic countries adhere to a healthier lifestyle and have better access to health care. Future studies should consider investigating further the association between health outcomes and determinants of health and how they are distributed in the Nordic societies.


[Specific features of wounds with a self-defense traumatic weapon "Osa"].
Specific features and outcomes of wounds with a traumatic weapon of self-defense "Osa" were analyzed in 24 patients. Mean age of the wounded was from 21 to76 years. In 20 patients there was a single wound, in 4 patients it was multiple, in 7--blunt, in 12--perforating and 5 patients had gutter wounds. All the patients were treated according to the principles of field military surgery. Five patients had severe wounds: penetrating fracture of the skull (2 of them died), fracture of the shoulder (1 case), injury of the main artery (1 case), of the pleura (1 case). The wounds were closed up by primary intention in 19 patients, by second intention in 4 patients. The authors' experience shows that a traumatic weapon of self-defense "Osa" rather often caused permanent harm to health and can be mortal. Active surgical strategy in treatment of such patients prevents the development of serious infectious complications.


Therapeutic aspects of Puerto Rican cult practices.
This paper seeks to explore the phenomenon of possession trance in the ritual context from still another tack, complementary to the studies cited above, by analyzing it as an active and perhaps necessary component in the development of significant personal relationships basic to the organization and goals of some religous cults.-1 This view has been suggested by data gathered in study of social process in Puerto Rican Spiritist cults-2 which examined the relationship between patterns of cult social organization and the cult execution of a culturally patterned psychotherapeutic process for committed adherents whose emotional problems are diagnosed by cult headers as manifestations of developing "faculties" for communication with the spirit world-3 (see Koss; Rogler and Hollingshead, 1965, pp. 244-254; Seda Bonilla, 1964).


Little evidence for niche partitioning among ectomycorrhizal fungi on spruce seedlings planted in decayed wood versus mineral soil microsites.
Ectomycorrhizal fungal (EMF) communities vary among microhabitats, supporting a dominant role for deterministic processes in EMF community assemblage. EMF communities also differ between forest and clearcut environments, responding to this disturbance in a directional manner over time by returning to the species composition of the original forest. Accordingly, we examined EMF community composition on roots of spruce seedlings planted in three different microhabitats in forest and clearcut plots: decayed wood, mineral soil adjacent to downed wood, or control mineral soil, to determine the effect of retained downed wood on EMF communities over the medium and long term. If downed and decayed wood provide refuge habitat distinct from that of mineral soil, we would expect EMF communities on seedlings in woody habitats in clearcuts to be similar to those on seedlings planted in the adjacent forest. As expected, we found EMF species richness to be higher in forests than clearcuts (P ≤ 0.01), even though soil nutrient status did not differ greatly between the two plot types (P ≥ 0.05). Communities on forest seedlings were dominated by Tylospora spp., whereas those in clearcuts were dominated by Amphinema byssoides and Thelephora terrestris. Surprisingly, while substrate conditions varied among microsites (P ≤ 0.03), especially between decayed wood and mineral soil, EMF communities were not distinctly different among microhabitats. Our data suggest that niche partitioning by substrate does not occur among EMF species on very young seedlings in high elevation spruce-fir forests. Further, dispersal limitations shape EMF community assembly in clearcuts in these forests.


[Effect of the lipopolysaccharide-protein complex of Pseudomonas syringae PV. atrofaciens on the process of tumor formation caused by Agrobacterium tumefaciens].
It has been found that the agent of bacterial spotting of rye P. syringae pv. atrofaciens 8281 has no antagonistic action on the strains 9052 and 9054 of Agrobacterium tumefaciens--the agent of crown gall tumor. Lipopolysaccharide-protein complex of P. syringae pv. atrofaciens 8281 when added to the culture medium does not affect the growth and development of A. tumefaciens bacteria. It has been experimentally established that the lipopolysaccharide-protein complex of P. syringae pv. atrofaciens 8281, when used to treat the potato explants before inoculation of A. tumefaciens, decreases induction and development of tumours on the explants. Tumour formation inhibition depends on concentration of lipopolysaccharide-protein complex solution.


PD-1 and PD-L1 inhibitors after platinum-based chemotherapy or in first-line therapy in cisplatin-ineligible patients: Dramatic improvement of prognosis and overall survival after decades of hopelessness in patients with metastatic urothelial cancer.
Until recently, there were no true innovations in the management of locally advanced (aUC) and metastatic urothelial cancer (mUC) in the last three decades. Vinflunine has been approved by the EMA (European Medicines Agency) with only limited improvement compared to best supportive care in second line treatment. In addition, gemcitabine/cisplatin has been established as an alternative to methotrexate, vinblastine, doxorubicin, and cisplatin (MVAC). The advent of checkpoint inhibitors (CPI) revolutionized the care of these patients, transforming a unanimously deadly disease into one with hope through sustained disease control. Five immune CPI have recently been approved for aUC/mUC by the US Food and Drug Administration (FDA) including atezolizumab, nivolumab, pembrolizumab, durvalumab and avelumab. All five CPI are FDA-approved as second-line therapy with atezolizumab and pembrolizumab also being approved for first-line therapy in cisplatin-ineligible patients. The rapid acceptance in the treatment algorithm of UC is based on the impressive clinical efficacy of these agents in some patients, combined with their excellent safety profile. These new agents are indeed the most important advancement in UC care. However, the challenge in the age of precision medicine is to identify the patients who are most likely to benefit from CPIs, as the majority of patients do not respond to CPI. Toward this goal, validation of clinical, molecular and imaging biomarkers that serve for prediction and monitoring of treatment response are of central necessity.


Detection of antibody in Aleutian disease of mink: comparison of enzyme-linked immunosorbent assay and counterimmunoelectrophoresis.
Experiments were undertaken to investigate the potential of the enzyme-linked immunosorbent assay (ELISA) as a screening test for the diagnosis of the 2 known naturally occurring forms of Aleutian disease of mink. Anti-Aleutian disease virus (ADV) antibody activity was not detectable in the sera of mink with nonprogressive Aleutian disease despite the demonstration of antibody by counterimmunoelectrophoresis (CIEP) in the same sera. Anti-ADV antibody was detectable in 93% of sera from mink at various stages of experimentally induced progressive Aleutian disease. False-negative reactions occurred in sera which demonstrated high anti-ADV antibody titers by CIEP. As a consequence of the high prevalence of false-negative reactions, the ELISA was not considered to be an effective screening test. However, using CIEP as an indicator of ADV infection, the ELISA may be useful in differentiating mink with nonprogressive Aleutian disease from mink with progressive Aleutian disease.


The economics of stone disease.
The rising prevalence of kidney stone disease is associated with significant costs to healthcare systems worldwide. This is in part due to direct procedural and medical management costs, as well as indirect costs to health systems, patients, and families. A number of manuscripts evaulating the economics of stone disease have been published since the 2008s International Consultation on Stone Disease. These highlight costs associated with stone disease, including acute management, surgical management, and medical management. This work hopes to highlight optimization in care by reducing inefficient treatments and maximizing cost-efficient preventative strategies.


The photoluminescence spectral profiles of water-soluble aggregates of PbS quantum dots assembled through reversible metal coordination.
Reversible coupling of glutathione-capped PbS quantum dots through coordination with Zn2+ cations forms water-soluble aggregates. These assemblies mediate multi-step hopping of near-infrared excitons through unity-quantum yield Förster resonance energy transfer. The photoluminescence spectra from these samples are sensitive indicators of average interparticle distance.


Multivisceral radical en bloc resection with spleen preservation in T4 gastric cancer.
Gastric cancers are the second most common cause of cancer death worldwide. In the majority of countries, gastric tumours are diagnosed at advanced stages. The authors present the case of a patient with a T4 gastric tumour who underwent a multivisceral en bloc resection (liver segmentectomy, total gastrectomy, partial pancreatectomy) and D2 lymphadenectomy with spleen preservation. The aim of this report was to confirm that, for T4 gastric tumours, radical resection can be performed without splenectomy with minimal morbidity, and this procedure can improve long-term survival.


Predicting Atrophy of the Cochlear Stria Vascularis from the Shape of the Threshold Audiogram.
Several lines of evidence have suggested that steeply sloping audiometric losses are caused by hair cell degeneration, while flat audiometric losses are caused by strial atrophy, but this concept has never been rigorously tested in human specimens. Here, we systematically compare audiograms and cochlear histopathology in 160 human cases from the archival collection of celloidin-embedded temporal bones at the Massachusetts Eye and Ear. The dataset included 106 cases from a prior study of normal-aging ears, and an additional 54 cases selected by combing the database for flat audiograms. Audiogram shapes were classified algorithmically into five groups according to the relation between flatness (i.e., SD of hearing levels across all frequencies) and low-frequency pure-tone average (i.e., mean at 0.25, 0.5, and 1.0 kHz). Outer and inner hair cell losses, neural degeneration, and strial atrophy were all quantified as a function of cochlear location in each case. Results showed that strial atrophy was worse in the apical than the basal half of the cochlea and was worse in females than in males. The degree of strial atrophy was uncorrelated with audiogram flatness. Apical atrophy was correlated with low-frequency thresholds and basal atrophy with high-frequency thresholds, and the former correlation was higher. However, a multivariable regression with all histopathological measures as predictors and audiometric thresholds as the outcome showed that strial atrophy was a significant predictor of threshold shift only in the low-frequency region, and, even there, the contribution of outer hair cell damage was larger.SIGNIFICANCE STATEMENT Cochlear pathology can only be assessed postmortem; thus, human cochlear histopathology is critical to our understanding of the mechanisms of hearing loss. Dogma holds that relative damage to sensory cells, which transduce mechanical vibration into electrical signals, versus the stria vascularis, the cellular battery that powers transduction, can be inferred by the shape of the audiogram, that is, down-sloping (hair cell damage) versus flat (strial atrophy). Here we quantified hair cell and strial atrophy in 160 human specimens to show that it is the degree of low-frequency hearing loss, rather than the audiogram slope, that predicts strial atrophy. Results are critical to the design of clinical trials for hearing-loss therapeutics, as current drugs target only hair cell, not strial, regeneration.


The Canadian Choosing Wisely campaign: the Canadian Hematology Society's top five tests and treatments.
Choosing Wisely Canada (CWC), a medical stewardship campaign, encourages dialogue between physicians and patients to promote high-quality decision-making. Medical societies develop lists of tests, treatments, and procedures that are unnecessary, reduce value, and may cause harm. The Canadian Hematology Society (CHS) elicited suggestions for CWC recommendations from its members and received 35 unique suggestions. A working group rated these based on their potential for harm, benefit, frequency of use and value. Twelve highly ranked items were subjected to systematic evidence review. The final items were included in the list if they were of sufficient evidence base and met pre-defined core principles. The CHS-CWC recommendations are: to avoid IVIG treatment for asymptomatic immune thrombocytopenia, not bridge warfarin in low-risk patients going for procedures, not perform thrombophilia testing in the workup of early pregnancy loss, avoid fine-needle aspiration in lymphoma diagnosis, and not transfuse red blood cells for an arbitrary hemoglobin threshold. Through implementation of these recommendations, physicians will reduce potential harm to patients and increase the value of health care.


Xylitol acts as an anticancer monosaccharide to induce selective cancer death via regulation of the glutathione level.
Herbal medicines and their bioactive compounds are increasingly being recognized as useful drugs for cancer treatments. The parasitic fungus Cordyceps militaris is an attractive anticancer herbal since it shows very powerful anticancer activity due to its phytocompound cordycepin. We previously discovered and reported that a high amount of xylitol is present in Cordyceps militaris extract, and that xylitol unexpectedly showed anticancer activity in a cancer-selective manner. We thus hypothesized that xylitol could become a useful supplement to help prevent various cancers, if we can clarify the specific machinery by which xylitol induces cancer cell death. It is also unclear whether xylitol acts on cancer suppression in vivo as well as in vitro. Here we show for the first time that induction of the glutathione-degrading enzyme CHAC1 is the main cause of xylitol-induced apoptotic cell death in cancer cells. The induction of CHAC1 is required for the endoplasmic reticulum (ER) stress that is triggered by xylitol in cancer cells, and is linked to a second induction of oxidative stress in the treated cells, and eventually leads to apoptotic cell death. Our in vivo approach also demonstrated that an intravenous injection of xylitol had a tumor-suppressing effect in mice, to which the xylitol-triggered ER stress also greatly contributed. We also observed that xylitol efficiently sensitized cancer cells to chemotherapeutic drugs. Based on our findings, a chemotherapeutic strategy combined with xylitol might improve the outcomes of patients facing cancer.


PEI-PEG-Chitosan Copolymer Coated Iron Oxide Nanoparticles for Safe Gene Delivery: synthesis, complexation, and transfection.
Gene therapy offers the potential of mediating disease through modification of specific cellular functions of target cells. However, effective transport of nucleic acids to target cells with minimal side effects remains a challenge despite the use of unique viral and non-viral delivery approaches. Here we present a non-viral nanoparticle gene carrier that demonstrates effective gene delivery and transfection both in vitro and in vivo. The nanoparticle system (NP-CP-PEI) is made of a superparamagnetic iron oxide nanoparticle (NP), which enables magnetic resonance imaging, coated with a novel copolymer (CP-PEI) comprised of short chain polyethylenimine (PEI) and poly(ethylene glycol) (PEG) grafted to the natural polysaccharide, chitosan (CP), which allows efficient loading and protection of the nucleic acids. The function of each component material in this nanoparticle system is illustrated by comparative studies of three nanoparticle systems of different surface chemistries, through material property characterization, DNA loading and transfection analyses, and toxicity assessment. Significantly, NP-CP-PEI demonstrates an innocuous toxic profile and a high level of expression of the delivered plasmid DNA in a C6 xenograft mouse model, making it a potential candidate for safe in vivo delivery of DNA for gene therapy.


Immediate postoperative of bariatric surgery in the intensive care unit versus an inpatient unit. A retrospective study with 828 patients.
To compare the incidence of complications and the duration of hospitalization of patients undergoing bariatric surgery admitted to the intensive care unit or a post-surgical hospitalization unit. This retrospective observational study included 828 patients admitted between January 2010 and February 2015 during the immediate postoperative period of bariatric surgery in a hospital. Data were collected via electronic medical records. The Mann-Whitney test was used to compare continuous variables, and the chi-square was used to compare categorical variables. Patients in both groups had similar demographic characteristics, with no significant differences in anthropometric data and comorbidities. There was no significant difference in the comparison of complications between the two groups. However, the group admitted to the intensive care unit had longer hospitalization times (median of 3 days versus 2 days, p < 0.05), and hospital costs were 8% higher. The present study found no benefit in the routine admittance of patients to the intensive care unit after undergoing bariatric surgery. This practice increased hospitalization time and hospital costs, which wasted resources. It is necessary to create objective criteria to identify patients requiring intensive care unit admission after bariatric surgery.


Centre-based day care for children younger than five years of age in low- and middle-income countries.
Because of poverty, children and families in low- and middle-income countries often face significant impediments to health and well-being. Centre-based day care services may influence the development of children and the economic situation of parents by providing good quality early childhood care and by freeing parents to participate in the labour force. To assess the effects of centre-based day care without additional interventions (e.g. psychological or medical services, parent training) on the development, health and well-being of children and families in low- and middle-income countries (as defined by the World Bank 2011). In April 2014, we searched CENTRAL, Ovid MEDLINE, EMBASE, PsycINFO, ERIC and 16 other sources, including several World Health Organization (WHO) regional databases. We also searched two trials registers, websites of government and non-government agencies and reference lists of relevant studies. We included randomised and quasi-randomised controlled trials and prospective non-randomised studies with contemporaneous control groups and assessments both before and after intervention. We considered non-randomised controlled trials, as centre-based care in low- and middle-income countries is unlikely to be studied using randomised controlled trials (Higgins 2011). We included the following outcomes: child intellectual development, child psychosocial development, maternal and family outcomes and incidence of infectious diseases. Two review authors independently assessed risk of bias and extracted data from the single included study. Only one trial, involving 256 children, met the inclusion criteria for this review. This study was assessed as having high risk of bias because of non-random allocation, incomplete outcome data and insufficient control of confounding factors. Results from this study suggest that centre-based day care may have a positive effect on child cognitive ability compared with no treatment (care at home) (assessed using a modified version of the British Ability Scale-II (BAS-II) (standardised mean difference (SMD) 0.74, 95% confidence interval (CI) 0.48 to 1.00, 256 participants, 1 study, very low-quality evidence). This study did not measure other variables relevant to this review. The single study included in this review provides limited evidence on the effects of centre-based day care for children younger than five years of age in low- and middle-income countries. This study was at high risk of bias and may have limited generalisability to other low- and middle-income countries. Many of the studies excluded from this review paired day care attendance with co-interventions that are unlikely to be provided in normal day care centres. Effectiveness studies on centre-based day care without these co-interventions are few, and the need for such studies is significant. In future studies, comparisons might include home visits or alternative day care arrangements.


De novo assembly of maritime pine transcriptome: implications for forest breeding and biotechnology.
Maritime pine (Pinus pinasterAit.) is a widely distributed conifer species in Southwestern Europe and one of the most advanced models for conifer research. In the current work, comprehensive characterization of the maritime pine transcriptome was performed using a combination of two different next-generation sequencing platforms, 454 and Illumina. De novo assembly of the transcriptome provided a catalogue of 26 020 unique transcripts in maritime pine trees and a collection of 9641 full-length cDNAs. Quality of the transcriptome assembly was validated by RT-PCR amplification of selected transcripts for structural and regulatory genes. Transcription factors and enzyme-encoding transcripts were annotated. Furthermore, the available sequencing data permitted the identification of polymorphisms and the establishment of robust single nucleotide polymorphism (SNP) and simple-sequence repeat (SSR) databases for genotyping applications and integration of translational genomics in maritime pine breeding programmes. All our data are freely available at SustainpineDB, the P. pinaster expressional database. Results reported here on the maritime pine transcriptome represent a valuable resource for future basic and applied studies on this ecological and economically important pine species.


Cell-free DNA is abundant in ascites and represents a liquid biopsy of ovarian cancer.
Malignant ascites is a common clinical feature of ovarian cancer and represents a readily accessible sample of tumour cells and tumour DNA. This study aimed to characterise the cell-free DNA (cfDNA) in ascites in terms of its size profile, stability and cell-free tumour DNA (cftDNA) content. Cell spheroids, loose cells and cell-free fluid was collected from ascites from 18 patients with ovarian cancer. cfDNA was isolated and assessed for size by electrophoresis, concentration by fluorometry,cftDNA content by methylation specific qPCR of HOXA9 and IFFO1 promoter regions and by targeted sequencing. Stability was assessed after ascites fluid was stored at 4 °C for 24 and 72 h before fractionating. The concentration of cfDNA in ascites ranged from 6.6 to 300 ng/mL. cfDNA size distribution resembled blood plasma-derived cfDNA, with major peaks corresponding to mono- and di-nucleosome DNA fragments. High molecular weight cfDNA was observed in 7 of 18 patients and appeared to be associated with extracellular vesicles. IFFO1 and HOXA9 methylation was proportionately higher in cfDNA than spheroid- and loose-cell fractions and was not observed in healthy primary cells. Variant allele frequency was highest in cfDNA compared to single cells and spheroids from ascites. Though cancer cell numbers in ascites declined to near zero in recurrent ascites from one patient undertaking chemotherapy, cftDNA could still be sampled. cfDNA size, concentration and tumour content was stable over 72 h. cfDNA in ovarian cancer ascites demonstrates inter-patient variability, yet is consistently a rich source of cftDNA, which is a stable substrate. This supports the wider clinical use of ascites in the molecular analysis of ovarian cancer.


The effect of nitrogen nutrition on cluster root formation and proton extrusion by Lupinus albus.
Nitrogen nutrition can influence cluster root formation in many wild species, but the effect of N form on cluster root formation and root exudation by white lupin is not known. In a solution culture study, we examined the effect of N nutrition (ammonium, nitrate, both or N2 fixation) on cluster root formation and H+ extrusion by white lupin plants under deficient and adequate P supply. The number of cluster roots increased greatly when plants were supplied with I microM P compared with 50 microM P, the increase being 7.8-fold for plants treated with (NH4)2SO4, 3-fold for plants treated with KNO3 and NH4NO3, and 2-4-fold for N2-fixing plants. Under P deficiency. NH4+-N supply resulted in production of a greater number and biomass of cluster roots than other N sources. Dry weight of cluster roots was 30 % higher than that of non-cluster roots in P-deficient plants treated with (NH4)2SO4 and NH4NO3. In plants treated with sufficient P (50 microM), the weight of non-cluster roots was approx. 90 % greater than that of cluster roots. Both total (micromol per plant h(-1)) and specific (micromol g(-1) root d. wt h(-1)) H+ extrusions were greatest from roots of plants supplied with (NH4)2SO4, followed by those supplied with NH4NO3 and N2 fixation, whereas plants receiving KNO3 had negative net H+ extrusion between the third and fifth week of growth (indicating uptake of protons or release of OH- ions). The rate of proton extrusion by NH4+-N-fed plants was similar under P-deficient and P-sufficient conditions. In contrast, proton exudation by N2-fixing plants and KNO3-treated plants was ten-fold greater under P deficiency than under P sufficiency. In comparison with P deficiency, plants treated with 50 microM P had a significantly higher concentration of P in roots, shoots and youngest expanded leaves (YEL). Compared with the N2 fixation and KNO3 treatments, total N concentration was highest in roots, shoots and YEL of plants supplied with (NH4)2SO4 and NH4NO3, regardless of P supply. Under P deficiency, K concentrations in roots decreased at all N supplies, especially in plants treated with (NH4)2SO4 and NH4NO3, which coincided with the greatest H+ extrusion at these P and N supplies. In conclusion, NH4-N nutrition stimulated cluster root formation and H+ extrusion by roots of P-deficient white lupin.


Color tuning of intrinsic white-light emission in anthracene-linker coordination networks.
White light-emitting diodes (WLEDs) have aroused great attention due to their potential technological applications. In this work, we present two new Zn(ii) anthracene-linker-driven coordination polymers that exhibit intrinsic white-light emission. The emission covers the whole visible spectrum at room temperature. The chromaticity coordinates of the broadband emission can be tuned under external stimuli, including thermal and mechanical grinding. The obtained coordination polymer materials emit a "warm" white light at room temperature suitable for indoor lighting applications as well as a "cold" white light at the cryogenic temperature. Hence, the well-defined structures and mechanically tunable emission provide an excellent opportunity for realizing their potential as white emitters in optoelectronics.


Impact of Oxygen Vacancy Occupancy on Charge Carrier Dynamics in BiVO4 Photoanodes.
Oxygen vacancies are ubiquitous in metal oxides and critical to performance, yet the impact of these states upon charge carrier dynamics important for photoelectrochemical and photocatalytic applications remains contentious and poorly understood. A key challenge is the unambiguous identification of spectroscopic fingerprints which can be used to track their function. Herein, we employ five complementary techniques to modulate the electronic occupancy of states associated with oxygen vacancies in situ in BiVO4 photoanodes, allowing us to identify a spectral signature for the ionization of these states. We obtain an activation energy of ∼0.2 eV for this ionization process, with thermally activated electron detrapping from these states determining the kinetics of electron extraction, consistent with improved photoelectrochemical performance at higher temperatures. Bulk, un-ionized states, however, function as deep hole traps, with such trapped holes energetically unable to drive water oxidation. These observations help address recent controversies in the literature regarding oxygen vacancy function, providing new insights into their impact upon photoelectrochemical performance.


Prediction of gestational weight gain - a biopsychosocial model.
To examine the influence of health behaviours and psychological well-being on gestational weight gain using a biopsychosocial model. A prospective cohort study of pregnant women consecutively recruited at their first antenatal care visit. A self-administered questionnaire was used to collect data on health behaviours and psychological well-being in early pregnancy. Linear regression and logistic regression were used to identify predictors of total weight gain in kilograms and weight gain outside the current Institute of Medicine recommendations, respectively. A maternity hospital in the Republic of Ireland. Data on 799 women were analysed. Pre-pregnant BMI ≥30·0 kg/m2, short stature, parity >0, decreased food intake and absence of health insurance predicted lower absolute gestational weight gain, while foreign nationality, consumption of takeaway meals more than once weekly and increased food intake predicted higher absolute gestational weight gain. Overweight and obesity, foreign nationality, increased food intake and height >170 cm were risk factors for excessive weight gain, while antenatal depression was protective against excessive weight gain. Notably, physical activity measures were not related to the gestational weight gain outcomes. Pre-pregnancy overweight and increased food intake were the strongest predictors of excessive gestational weight gain. None of the psychological well-being measures examined, with the exception of antenatal depression, was associated with any of the weight gain outcomes. The behavioural predictors of gestational weight gain were increased food intake and takeaway consumption. Public health promotions should target pre-pregnancy BMI and pregnancy-associated change in food intake.


The association between varicella zoster virus and dementia: a systematic review and meta-analysis of observational studies.
The relationship between varicella zoster virus (VZV) infection and the risk of dementia has not been previously studied specifically. Therefore, this study sought to determine the relationship between studying VZV infection and dementia occurring in the general population by conducting an extensive meta-analysis of published cases. A systematic literature search was conducted in seven online databases by October 31, 2022. Heterogeneity was tested by the I2 index. Pooled HR and 95% CI were used to estimate the effect of VZV infection on dementia. Sensitivity analyses and publication bias were also performed. Nine studies involving 3,326,673 subjects were included. VZV infection was associated with an increased risk of dementia (HR = 1.11, 95% CI: 1.02-1.21). The risk of dementia was reduced in those who received antiviral therapy compared to those who did not (HR = 0.84, 95% CI: 0.71-0.99). In addition, VZV infection was found to be associated with an increased risk of developing dementia in the pooled results of the moderate quality study (HR = 1.81,95% CI: 1.27-2.59), and this association persisted when subgroup analyses were performed based on region (Asia: HR = 1.18,95% CI: 1.04-1.33). Our results suggest that VZV infection might increase the risk of developing dementia, but there is no clear mechanism about the true relationship, and since there is no effective treatment for dementia, and our results suggest that some populations can benefit from antiviral therapy, it is at least arguable that patients who develop VZV infection should be treated with appropriate antiviral medications.


The EIPeptiDi tool: enhancing peptide discovery in ICAT-based LC MS/MS experiments.
Isotope-coded affinity tags (ICAT) is a method for quantitative proteomics based on differential isotopic labeling, sample digestion and mass spectrometry (MS). The method allows the identification and relative quantification of proteins present in two samples and consists of the following phases. First, cysteine residues are either labeled using the ICAT Light or ICAT Heavy reagent (having identical chemical properties but different masses). Then, after whole sample digestion, the labeled peptides are captured selectively using the biotin tag contained in both ICAT reagents. Finally, the simplified peptide mixture is analyzed by nanoscale liquid chromatography-tandem mass spectrometry (LC-MS/MS). Nevertheless, the ICAT LC-MS/MS method still suffers from insufficient sample-to-sample reproducibility on peptide identification. In particular, the number and the type of peptides identified in different experiments can vary considerably and, thus, the statistical (comparative) analysis of sample sets is very challenging. Low information overlap at the peptide and, consequently, at the protein level, is very detrimental in situations where the number of samples to be analyzed is high. We designed a method for improving the data processing and peptide identification in sample sets subjected to ICAT labeling and LC-MS/MS analysis, based on cross validating MS/MS results. Such a method has been implemented in a tool, called EIPeptiDi, which boosts the ICAT data analysis software improving peptide identification throughout the input data set. Heavy/Light (H/L) pairs quantified but not identified by the MS/MS routine, are assigned to peptide sequences identified in other samples, by using similarity criteria based on chromatographic retention time and Heavy/Light mass attributes. EIPeptiDi significantly improves the number of identified peptides per sample, proving that the proposed method has a considerable impact on the protein identification process and, consequently, on the amount of potentially critical information in clinical studies. The EIPeptiDi tool is available at http://bioingegneria.unicz.it/~veltri/projects/eipeptidi/ with a demo data set. EIPeptiDi significantly increases the number of peptides identified and quantified in analyzed samples, thus reducing the number of unassigned H/L pairs and allowing a better comparative analysis of sample data sets.


The influence of hyperthyroidism and hypothyroidism on alpha- and beta-adrenergic receptor systems and adrenergic responsiveness.
A detailed review has been conducted of studies addressing dressing the subject of the influence of thyroid hormone on alpha- and beta-adrenergic receptors and adrenergic responsiveness in a wide range of experimental animals and tissues. The studies summarized in the present article have been restricted to those in which explicit measurements of receptor number were made by the use of appropriate radioligands. Particular emphasis is given to an examination of the relationship between thyroid hormone-induced changes in alpha- and beta-adrenergic receptor number and accompanying changes in adenylate cyclase activity and more distal adrenergic responses. Although in many instances thyroid hormone-induced changes in receptor number are reflected in coordinate changes in adrenergic sensitivity, this is shown to be by no means uniformly the case. In contrasting instances, modifications at other more distal sites in the sequence of events mediating catecholamine hormone action are responsible for biochemical and physiological changes in catecholamine responsiveness induced by thyroid hormone.


Induced membranes secrete growth factors including vascular and osteoinductive factors and could stimulate bone regeneration.
Based on a new concept, a procedure combining induced membranes and cancellous autografts allows the reconstruction of wide diaphyseal defects. In the first stage of this procedure, a cement spacer is inserted into the defect; the spacer is responsible for the formation of a pseudo-synovial membrane. In the second stage, the defect is reconstructed two months later by an autologous cancellous bone graft. The aim of this study was to evaluate the histological and biochemical characteristics of these membranes induced in rabbits. Histological studies carried out two, four, six, and eight weeks following implantation revealed a rich vascularization. Qualitative and quantitative immunochemistry showed production of growth factors (VEGF, TGFbeta1) and osteoinductive factors (BMP-2). Maximum BMP-2 production was obtained four weeks after the implantation, and, at this time, induced membranes favored human bone marrow stromal cell differentiation to the osteoblastic lineage. Should these results be confirmed in humans, bone reconstruction could be carried out earlier than previously thought and in better conditions than expected, the membrane playing the role of an in situ delivery system for growth and osteoinductive factors.


Ongoing outbreak of measles in Oslo, Norway, January-February 2011.
Between 19 January and 17 February 2011, 10 cases of measles (eight laboratory-confirmed and two probable) were reported in Oslo with the majority of cases in a mainly unvaccinated immigrant community. Of these, two cases were identified outside the immigrant community, in Norwegian children.


Orienting asymmetries and physiological reactivity in dogs' response to human emotional faces.
Recent scientific literature shows that emotional cues conveyed by human vocalizations and odours are processed in an asymmetrical way by the canine brain. In the present study, during feeding behaviour, dogs were suddenly presented with 2-D stimuli depicting human faces expressing the Ekman's six basic emotion (e.g. anger, fear, happiness, sadness, surprise, disgust, and neutral), simultaneously into the left and right visual hemifields. A bias to turn the head towards the left (right hemisphere) rather than the right side was observed with human faces expressing anger, fear, and happiness emotions, but an opposite bias (left hemisphere) was observed with human faces expressing surprise. Furthermore, dogs displayed higher behavioural and cardiac activity to picture of human faces expressing clear arousal emotional state. Overall, results demonstrated that dogs are sensitive to emotional cues conveyed by human faces, supporting the existence of an asymmetrical emotional modulation of the canine brain to process basic human emotions.


Thymic hyperplasia after high-dose chemotherapy and autologous stem cell transplantation: incidence and significance in patients with breast cancer.
The purpose of this study was to determine the incidence and clinical significance of thymic hyperplasia after high-dose chemotherapy and autologous stem cell transplantation for treatment of metastatic or high-risk primary (with at least four positive lymph nodes) breast cancer. We retrospectively reviewed clinical records and CT scans of 102 breast cancer patients treated with high-dose chemotherapy and autologous stem cell transplantation. Patients were 26-63 years old (mean, 46 years). The length and width of the thymus gland were measured on serial CT scans obtained before and after treatment. Moderate thymic hyperplasia was recorded if a focal or diffuse increase was seen in the oblong, triangular soft-tissue opacity conforming to the configuration of the normal gland within the anterior mediastinum after therapy. Minimal hyperplasia was recorded when a minimal increase was seen in soft-tissue attenuation conforming to the configuration of the normal bilobed thymus gland within the anterior mediastinum, but no discrete mass was visible. CT showed no thymic hyperplasia in 91 (89%) of the 102 patients. CT showed thymic hyperplasia in the other 11 patients (11%). Three patients (3%) had moderate hyperplasia, and eight patients (8%) had minimal hyperplasia. When comparing patients with and without hyperplasia, we found no difference in mean age or survival. Thymic hyperplasia is rare after high-dose chemotherapy and autologous stem cell transplantation in adult patients with metastatic or high-risk primary breast cancer. In this population, thymic hyperplasia does not appear to correlate with survival.


BET 2: Caffeine as an analgesic adjunct in tension-type headache and migraine.
A short-cut review of the literature was carried out to examine the benefits of caffeine as an analgesic adjunct in tension-type and migraine-type headache. Six papers were identified as suitable for inclusion using the reported search strategy. The author, date and country of publication, patient group studied, study type, relevant outcomes, results and study weaknesses of the best papers are tabulated. It is concluded that caffeine provides effective analgesia as an adjunctive treatment in the management of secondary headache syndromes.


Juvenile skeletogenesis in anciently diverged sea urchin clades.
Mechanistic understanding of evolutionary divergence in animal body plans devolves from analysis of those developmental processes that, in forms descendant from a common ancestor, are responsible for their morphological differences. The last common ancestor of the two extant subclasses of sea urchins, i.e., euechinoids and cidaroids, existed well before the Permian/Triassic extinction (252 mya). Subsequent evolutionary divergence of these clades offers in principle a rare opportunity to solve the developmental regulatory events underlying a defined evolutionary divergence process. Thus (i) there is an excellent and fairly dense (if yet incompletely analyzed) fossil record; (ii) cladistically confined features of the skeletal structures of modern euechinoid and cidaroid sea urchins are preserved in fossils of ancestral forms; (iii) euechinoids and cidaroids are among current laboratory model systems in molecular developmental biology (here Strongylocentrotus purpuratus [Sp] and Eucidaris tribuloides [Et]); (iv) skeletogenic specification in sea urchins is uncommonly well understood at the causal level of interactions of regulatory genes with one another, and with known skeletogenic effector genes, providing a ready arsenal of available molecular tools. Here we focus on differences in test and perignathic girdle skeletal morphology that distinguish all modern euechinoid from all modern cidaroid sea urchins. We demonstrate distinct canonical test and girdle morphologies in juveniles of both species by use of SEM and X-ray microtomography. Among the sharply distinct morphological features of these clades are the internal skeletal structures of the perignathic girdle to which attach homologous muscles utilized for retraction and protraction of Aristotles׳ lantern and its teeth. We demonstrate that these structures develop de novo between one and four weeks after metamorphosis. In order to study the underlying developmental processes, a method of section whole mount in situ hybridization was adapted. This method displays current gene expression in the developing test and perignathic girdle skeletal elements of both Sp and Et juveniles. Active, specific expression of the sm37 biomineralization gene in these muscle attachment structures accompanies morphogenetic development of these clade-specific features in juveniles of both species. Skeletogenesis at these clade-specific muscle attachment structures displays molecular earmarks of the well understood embryonic skeletogenic GRN: thus the upstream regulatory gene alx1 and the gene encoding the vegfR signaling receptor are both expressed at the sites where they are formed. This work opens the way to analysis of the alternative spatial specification processes that were installed at the evolutionary divergence of the two extant subclasses of sea urchins.


Parental socio-economic status and risk of first admission with schizophrenia- a Danish national register based study.
We examined the relationships between measures of parental and personal socio-economic status and risk of first admission with schizophrenia in order to identify whether low socio-economic status in cases is a consequence of the illness process or is a familial risk factor. A national population-based nested case-control study based on Danish longitudinal registers was conducted. The sample included 7704 first admissions with ICD-8 or ICD-10 schizophrenia admitted to a psychiatric facility in Denmark between 1981 and 1998 and 192590 individually time-, age- and gender-matched population controls identified through national registers, and their parents and siblings. Socio-economic indicators measured in the year prior to admission and background factors for cases, controls, and parents were included. Risk of schizophrenia was associated with unemployment, low educational attainment, being single, lower wealth status, low income, and being childless. Increased risk was associated with a family history of psychiatric disorders, birth in urban areas, birth outside of Denmark, and having three of more siblings. Increased risk of schizophrenia was associated with parental unemployment and parental lower income, but was not associated with parental wealth. Risk for schizophrenia was associated with higher education in parents. Increased risk of first admission was associated with socio-economic disadvantage in cases. Although we found some associations between parental unemployment and parental higher education and risk of schizophrenia, there was little evidence that low parental socio-economic status increases the risk of schizophrenia.


Association of Bergmeister Papilla and Deep Optic Nerve Head Structures With Prelaminar Schisis of Normal and Glaucomatous Eyes.
To investigate factors associated with the severity of prelaminar schisis (PLS) in heathy subjects and glaucoma patients. Prospective cross-sectional study. A total of 217 eyes of 217 subjects (110 normal eyes and 107 open angle glaucoma eyes) were studied. Frequency and severity of PLS were compared between normal and glaucomatous eyes. Multivariate logistic models were used to assess factors associated with the severity of PLS. Factors considered were age, axial length, glaucomatous damage indices, Bruch membrane opening (BMO) and anterior scleral canal opening parameters, tractional forces (posterior vitreous staging and presence of Bergmeister papilla), circumpapillary choroidal thickness, lamina cribrosa (LC) parameters, and peripapillary scleral (PPS) angle. The frequency of PLS was 70.9% in normal eyes and 72.0% in glaucomatous eyes. There was no difference in frequency and severity between the groups. The presence of Bergmeister papilla was the strongest predictor of a more severe PLS in both normal and glaucomatous eyes (odds ratio [OR] + 9.78, 12.5; both P < .001). A larger PPS angle in normal eyes (OR = 1.19; P = .003) and a larger BMO area and a deeper LC depth in glaucomatous eyes (OR = 1.08, 1.05; both P = .038) were associated with severity of PLS. The severity of PLS was strongly associated with the presence of Bergmeister papilla, suggesting a traction-related phenomenon. Correlation of PLS severity with larger BMO area and deeper LC depth, which are optic nerve head structures associated with glaucoma, suggested its possible relationship with glaucomatous damage.


Evaluation of photo-reactive siderophore producing bacteria before, during and after a bloom of the dinoflagellate Lingulodinium polyedrum.
Evidence is increasing for a mutualistic relationship between phytoplankton and heterotrophic marine bacteria. It has been proposed that bacteria producing photoactive iron binding compounds known as siderophores could play an important role in such mutualistic associations by producing bioavailable iron utilizable by phytoplankton and in exchange receive autotrophically derived DOM. In order to understand the potential role photoactive siderophores might be playing in bacterial-algal mutualism or marine biogeochemistry in general, it is important to be able to detect and quantify their presence in various environments. One approach to accomplish that end is to make use of high sensitivity genomics technology (qPCR) to search for siderophore biosynthesis genes related to the production of photoactive siderophores. In this way one can access their "biochemical potential" and utilize this information as a proxy for the presence of these siderophores in the marine environment. In this report we studied the correlation of the presence of bacteria producing one of the three photoactive siderophores relative to total bacterial and dinoflagellate numbers from surface water at the Scripps Pier before, during, and after fall bloom of the dinoflagellate Lingulodinium polyedrum. We believe that these findings will aid us in gauging the importance of photoactive siderophores in the marine environment and in harmful algal bloom dynamics in particular.


Evaluation of oxidative stress and antioxidant parameters in children with carbon monoxide poisoning.
In this study, we aimed to investigate oxidative stress and antioxidant parameter levels in patients with carbon monoxide (CO) poisoning. The study was conducted prospectively between March 1, 2015 and April 30, 2016 in the pediatric emergency department. Eligible patients included children aged 0-18 years old with a diagnosis of CO poisoning. To determination of oxidative stress and antioxidant parameter levels, venous blood with heparinized and urine samples were drawn during the admission and after normobaric oxygen (NBO) and hyperbaric oxygen (HBO) treatment. Forty-seven children with CO poisoning for study group and 29 patients as control group were included to the study. Sixteen patients treated with HBO. Basal plasma malondialdehyde levels were found to be significantly higher in the CO poisoning group when compared with the control group (p = 0.019). There is no significant difference in oxidative stress and antioxidant parameter levels except erythrocyte catalase enzyme levels in patients treated with NBO when comparing before and after NBO treatment (p > 0.05). Decreasing of basal erythrocyte catalase enzyme levels were found statistically significant after NBO treatment (p = 0.04). There was no significant difference in oxidative stress and antioxidant parameter levels in patients treated with HBO before and after therapy (p > 0.05). CO poisoning is associated with increased lipid peroxidation in children immediately after the poisoning. However, both treatment modalities including NBO or HBO do not have a significant effect on oxidative stress or antioxidant parameter levels.


Poor quality of sperm as it affects repeated early pregnancy loss.
A study was carried out to determine whether males contribute to repeated early pregnancy loss. Semen samples were analyzed from proven-fertile men (n = 51 group I) and from men whose partners presented with early pregnancy loss (>3 first trimester abortions, n = 32 group II). Routine analysis, sperm function tests, and ultrastructural studies of sperms were carried out. Female factor could be identified in 25 (78%) couples, and in 7 (22%) no cause either male or female could be identified and the semen analysis was normal. Percent morphologically normal did not differ significantly between the groups, but increased sperm head abnormalities were seen. The functional tests were all normal except for a significant decrease in the capacity of nuclear chromatin to decondense in vitro. The ultrastructural studies showed defects of chromatin condensation and irregular nuclei with vacuoles. This study points to the loss of chromatin integrity as a possible contributing factor from males to early pregnancy loss.


Immunopathology of ANCA-associated vasculitis.
During the past few years remarkable progress has been achieved in the understanding of the pathogenic mechanisms leading to vascular inflammation and injury in ANCA-associated vasulitides (AAV): Wegener's granulomatosis (WG), microscopic polyangiitis (MPA) and Churg Strauss syndrome (CSS). In this paper we review the immunopathology of these diseases by describing the role of autoantibodies (ANCA), dysregulation and abnormalities at the cellular level, genetic background and environmental factors that predispose to autoimmune response.


Abundant and diverse clustered regularly interspaced short palindromic repeat spacers in Clostridium difficile strains and prophages target multiple phage types within this pathogen.
Clostridium difficile is an important human-pathogenic bacterium causing antibiotic-associated nosocomial infections worldwide. Mobile genetic elements and bacteriophages have helped shape C. difficile genome evolution. In many bacteria, phage infection may be controlled by a form of bacterial immunity called the clustered regularly interspaced short palindromic repeats/CRISPR-associated (CRISPR/Cas) system. This uses acquired short nucleotide sequences (spacers) to target homologous sequences (protospacers) in phage genomes. C. difficile carries multiple CRISPR arrays, and in this paper we examine the relationships between the host- and phage-carried elements of the system. We detected multiple matches between spacers and regions in 31 C. difficile phage and prophage genomes. A subset of the spacers was located in prophage-carried CRISPR arrays. The CRISPR spacer profiles generated suggest that related phages would have similar host ranges. Furthermore, we show that C. difficile strains of the same ribotype could either have similar or divergent CRISPR contents. Both synonymous and nonsynonymous mutations in the protospacer sequences were identified, as well as differences in the protospacer adjacent motif (PAM), which could explain how phages escape this system. This paper illustrates how the distribution and diversity of CRISPR spacers in C. difficile, and its prophages, could modulate phage predation for this pathogen and impact upon its evolution and pathogenicity. Clostridium difficile is a significant bacterial human pathogen which undergoes continual genome evolution, resulting in the emergence of new virulent strains. Phages are major facilitators of genome evolution in other bacterial species, and we use sequence analysis-based approaches in order to examine whether the CRISPR/Cas system could control these interactions across divergent C. difficile strains. The presence of spacer sequences in prophages that are homologous to phage genomes raises an extra level of complexity in this predator-prey microbial system. Our results demonstrate that the impact of phage infection in this system is widespread and that the CRISPR/Cas system is likely to be an important aspect of the evolutionary dynamics in C. difficile.


Molecular dynamics studies on the domain swapped Salmonella typhimurium survival protein SurE: insights on the possible reasons for catalytic cooperativity.
Stationary phase survival protein SurE from Salmonella typhimurium is a dimeric protein formed by the swapping of a tetramerization loop involved in the formation of a loose tetramer and a C-terminal helix. It functions as a phosphatase. The two-fold symmetry of the dimeric protein was lost in the mutants H234A and D230A/H234A in which a crucial hydrogen bond in the hinge involved in C-terminal helix swapping was eliminated. The catalytic activity of both mutants was drastically reduced. In contrast to the native protein, H234A exhibited positive cooperativity in its catalytic activity. In order to relate these observations to the dynamics of the native and distorted mutants, molecular dynamics (MD) simulations were carried out using GROMACS v4.0.7. In all the simulations, the swapped segments and a segment near the active site were found to be highly flexible. These segments exhibited distinct dynamic features in the two protomers (A and B) of the dimeric protein. The dimeric organization was more significantly affected in the mutants when compared to the native structure, suggesting that the mutations enhance the intrinsic flexibility of the protein. The larger flexibility of the mutants affects the relative movement between the loops near the two active sites. The positive cooperativity observed in H234A mutant is most likely due to this increased flexibility and loop movement.


Assessment of the humoral immune response against Plasmodium falciparum rhoptry-associated proteins 1 and 2.
Naturally occurring antibody responses to Plasmodium falciparum rhoptry-associated proteins 1 and 2 (RAP-1 and RAP-2) were measured with recombinant and parasite-derived forms of the antigens. For comparative purposes, responses to multiple forms of three other malarial antigens were also examined. The sera of 100 Papua New Guineans were screened for antibodies. Eighty-six and 82% of individuals over 30 years of age had antibodies that recognized parasite-derived RAP-1 and RAP-2, respectively. Importantly, we found that recombinant and native antigens share linear epitopes seen by the human immune system; thus, the recombinant proteins may be adequate human immunogens. However, antibodies affinity purified on recombinant RAP-1 reacted with other antigens in addition to parasite-derived RAP-1. Thus, the antigenicity of RAP-1 may have been overestimated previously. The recognition of RAP-1 and RAP-2 correlated with age and with the recognition of recombinant forms of the ring-infected erythrocyte surface antigen, merozoite surface protein 1, and merozoite surface antigen 2 (MSA2) antigens. Antibodies to these antigens appear to be generated in response to the total exposure to malaria of the host. Antibodies to conserved regions of MSA2 had stronger correlations with both age and the recognition of other antigens than did the full-length recombinant MSA2 molecule. In contrast to results with the other antigens, there was no significant difference in the ages of individuals with a certain antibody titer to the full-length recombinant or parasite-derived MSA2 molecule, but antibodies to these two antigens did correlate with parasitemia. For all antigens tested, antibody levels after two infections can approach the peak levels of antibodies obtained in immune individuals.


Heritability and validity of healthy physical aging (wellness) in elderly male twins.
The authors define a trait "wellness" for good health in 6109 men in the National Academy of Sciences-National Research (NAS-NRC) twin panel aged 70 years and up surveyed by mail in the fall of 1998. Men who responded that they had not had a heart attack, coronary surgery, stroke, diabetes or prostate cancer in the survey questionnaire (Q8) met the broad definition of wellness. A more narrow definition included the absence of hypertension. Genetic analysis indicated that over 50% of the population variance for liability to either wellness definition was genetic. A subset of the NAS-NRC twins also participates in the National Heart, Lung and Blood Institute (NHLBI) twin study. NHLBI examinations and medical record review was done in 1986-1987 and 1995-1997 for 389 individuals who completed Q8. Excellent agreement (kappa > 0.8) was found between Q8 and outcome review for each condition comprising the wellness definition, ranging from 0.81 for coronary surgery to 0.88 for diabetes. Substantial agreement (kappa = 0.67) was found for hypertension. Kappa values for wellness were 0.82 for the broader definition and 0.74 if high blood pressure was included. Fraternal twin-pairs concordant for the wellness definitions are currently being recruited for linkage studies.


Epigenetics and psychostimulant addiction.
Chronic drug exposure alters gene expression in the brain and produces long-term changes in neural networks that underlie compulsive drug taking and seeking. Exactly how drug-induced changes in synaptic plasticity and subsequent gene expression are translated into persistent neuroadaptations remains unclear. Emerging evidence suggests that complex drug-induced neuroadaptations in the brain are mediated by highly synchronized and dynamic patterns of gene regulation. Recently, it has become clear that epigenetic mechanisms contribute to drug-induced structural, synaptic, and behavioral plasticity by regulating expression of gene networks. Here we review how alterations in histone modifications, DNA methylation, and microRNAs regulate gene expression and contribute to psychostimulant addiction with a focus on the epigenetic mechanisms that regulate brain-derived neurotrophic factor (BDNF) expression following chronic cocaine exposure. Identifying epigenetic signatures that define psychostimulant addiction may lead to novel, efficacious treatments for drug craving and relapse.


Achieving Ultralow, Zero, and Inverted Tunneling Attenuation Coefficients in Molecular Wires with Extended Conjugation.
Molecular tunnel junctions are organic devices miniaturized to the molecular scale. They serve as a versatile toolbox that can systematically examine charge transport behaviors at the atomic level. The electrical conductance of the molecular wire that bridges the two electrodes in a junction is significantly influenced by its chemical structure, and an intrinsically poor conductance is a major barrier for practical applications toward integrating individual molecules into electronic circuitry. Therefore, highly conjugated molecular wires are attractive as active components for the next-generation electronic devices, owing to the narrow highest occupied molecular orbital-lowest occupied molecular orbital gaps provided by their extended π-building blocks. This article aims to highlight the significance of highly conductive molecular wires in molecular electronics, the structures of which are inspired from conductive organic polymers, and presents a body of discussion on molecular wires exhibiting ultralow, zero, or inverted attenuation of tunneling probability at different lengths, along with future directions.


Impact of Subsidies and Socioeconomic Status on Varicella Vaccination in Greater Tokyo, Japan.
Although the control of varicella outbreaks is an important health issue, cost could present a major barrier for vaccination. The aim of this study is to investigate the association of vaccine subsidies and caregivers' socioeconomic status with varicella vaccine coverage of their children in Greater Tokyo, Japan, before the period that varicella vaccination was included in routine immunization program. Participants were recruited from two different cities. In Chiba city, parents of 18-month-old infants (N = 378) undergoing a medical examination in July 2013 were recruited at a clinic where no subsidy for varicella immunization was provided. In Nishitokyo city, parents of 24- to 30-month-old children (N = 315) undergoing a health checkup in July and August 2013 were recruited at a clinic where a partial subsidy was provided. The association between household income and varicella immunization was investigated by multivariate logistic regression stratified by city. Vaccine coverage was 61.0% in Chiba city and 73.3% in Nishitokyo city. In Chiba city, odds ratios of middle and high household income for varicella immunization were 4.22 [95% confidence interval (CI): 1.65-10.7] and 5.94 (95% CI: 1.89-18.6), respectively, compared to low household income. However, household income was not associated with varicella vaccination in Nishitokyo city. Neither working status nor education was associated with vaccination in both cities. While household income was associated with high vaccine coverage in the city with no vaccine subsidy, this association was not observed in the city where the subsidy was given, which suggests that cost is a barrier for varicella immunization. Thus, in countries where varicella vaccination is not included in routine immunization programs, introducing subsidies nationwide or routine immunization programs for varicella vaccination would be an important approach to eliminate inequality in vaccine coverage.


Atherosclerosis: an infectious disease?
Traditional risk factors do not fully account for atherogenesis. There is increasing evidence that infectious pathogens, such as Helicobacter pylori, cytomegalovirus, and Chlamydia pneumoniae, may promote the atherosclerotic cascade. Proposed mechanisms include macrophage transformation, endothelial injury, chronic inflammation, and thrombosis. Specific antibiotic therapy may affect outcome.


Observation of the shallow 2 Π 1 state of NaH.
The 2 1Π state of NaH has been observed up to the last bound vibrational level using pulsed optical-optical double resonance fluorescence depletion spectroscopy. A total of 20 rovibrational energy levels ( v = 2-4 and J = 1-9) were assigned to this electronic state by means of comparing the successive rovibrational spectra to the eigenvalues of the ab initio potential energy curve. The decrease of background fluorescence near the atomic asymptotic limit Na(3d) + H(1s) is an indication of reaching the dissociation limit of the NaH 2 1Π state. Unobserved rovibrational levels ( v = 0 and 1) are due to poor Franck-Condon overlap of 2 1Π ← A 1Σ+ transition within the accessible rovibrational levels of intermediate A 1Σ+ state of this work.