Specific NuRD components are required for fin regeneration in zebrafish.
Epimorphic regeneration of a missing appendage in fish and urodele amphibians involves the creation of a blastema, a heterogeneous pool of progenitor cells underneath the wound epidermis. Current evidence indicates that the blastema arises by dedifferentiation of stump tissues in the vicinity of the amputation. In response to tissue loss, silenced developmental programs are reactivated to form a near-perfect copy of the missing body part. However, the importance of chromatin regulation during epimorphic regeneration remains poorly understood. We found that specific components of the Nucleosome Remodeling and Deacetylase complex (NuRD) are required for fin regeneration in zebrafish. Transcripts of the chromatin remodeler chd4a/Mi-2, the histone deacetylase hdac1/HDAC1/2, the retinoblastoma-binding protein rbb4/RBBP4/7, and the metastasis-associated antigen mta2/MTA were specifically co-induced in the blastema during adult and embryonic fin regeneration, and these transcripts displayed a similar spatial and temporal expression patterns. In addition, chemical inhibition of Hdac1 and morpholino-mediated knockdown of chd4a, mta2, and rbb4 impaired regenerative outgrowth, resulting in reduction in blastema cell proliferation and in differentiation defects. Altogether, our data suggest that specialized NuRD components are induced in the blastema during fin regeneration and are involved in blastema cell proliferation and redifferentiation of osteoblast precursor cells. These results provide in vivo evidence for the involvement of key epigenetic factors in the cellular reprogramming processes occurring during epimorphic regeneration in zebrafish.


[Eating disorders risk assessment on semi-professional male team sports players].
Introduction: eating disorders (EDs) are characterized by an extreme concern about body weight and body image. Male team sports players are usually excluded from the population at risk of developing EDs. This exemption can be questioned based on previous studies identifying a great body concern in male team athletes along with a increase of the sport-thinness relation. Objective: to detect EDs symptoms and to assess risk factors of its development in male team sports players. Methodology: a descriptive-analytical study was carried out with 49 male adult semiprofessional team sports players (football, basketball and rugby) between 18 and 35 years old. All subjects authorized their participation through informed consent. Data was collected through a general assessment sheet along with four validates tools: the Eating Habits Questionnaire for Athletes (CHAD), the Test of Food Attitudes (EAT-40), the Inventory of Eating (EDI-2), and the Questionnaire on the Body Shape (BSQ). All data were analyzed with a Kolmogorov-Smirnov, Student's t, ANOVA and Pearson correlation. Results: it was observed that 14% of the subjects presented symptoms of EDs. Positive correlation was observed between score of the questionnaires, weekly training load and body mass index. Also football players score and rugbiers score were higher than basketball players score. Conclusion: male sports team players could also be a group of risk for EDs development. EDs risk greats when BMI and weekly training load high.


High genetic diversity and structured populations of the oriental fruit moth in its range of origin.
The oriental fruit moth Grapholita ( = Cydia) molesta is a key fruit pest globally. Despite its economic importance, little is known about its population genetics in its putative native range that includes China. We used five polymorphic microsatellite loci and two mitochondrial gene sequences to characterize the population genetic diversity and genetic structure of G. molesta from nine sublocations in three regions of a major fruit growing area of China. Larval samples were collected throughout the season from peach, and in late season, after host switch by the moth to pome fruit, also from apple and pear. We found high numbers of microsatellite alleles and mitochondrial DNA haplotypes in all regions, together with a high number of private alleles and of haplotypes at all sublocations, providing strong evidence that the sampled area belongs to the origin of this species. Samples collected from peach at all sublocations were geographically structured, and a significant albeit weak pattern of isolation-by-distance was found among populations, likely reflecting the low flight capacity of this moth. Interestingly, populations sampled from apple and pear in the late season showed a structure differing from that of populations sampled from peach throughout the season, indicating a selective host switch of a certain part of the population only. The recently detected various olfactory genotypes in G. molesta may underly this selective host switch. These genetic data yield, for the first time, an understanding of population dynamics of G. molesta in its native range, and of a selective host switch from peach to pome fruit, which may have a broad applicability to other global fruit production areas for designing suitable pest management strategies.


Pharmacotherapy of heparin-induced thrombocytopenia: therapeutic options and challenges in the clinical practices.
Heparin-induced thrombocytopenia (HIT) is an immune response to heparin associated with significant morbidity and mortality in hospitalized patients if unidentified as soon as possible, owing to thromboembolic complications involving both arterial and venous systems. Early diagnoses based on a comprehensive interpretation of clinical and laboratory information improves clinical outcomes. Management principles of strongly suspected HIT should not be delayed for laboratory result confirmation. Treatment strategies have been introduced including new, safe, and effective agents. This review summarizes the clinical therapeutic options for HIT addressing the use of parenteral direct thrombin inhibitors and indirect factor Xa inhibitors as well as the potential non-vitamin K antagonist oral anticoagulants.


Restriction mapping of a new deletion responsible for G gamma (delta beta)o thalassemia.
DNA from individuals heterozygous for (G)gamma(deltabeta)(o) thalassaemia has been studied by restriction endonuclease analysis. The results reveal a new molecular defect associated with this condition. A total of three defects is now responsible for the one single phenotype, thereby emphasising the complex relationship between genotype and phenotype among the disorders of beta-like globin synthesis in man.


Molecular and idiotypic analyses of the antibody response to Cryptococcus neoformans glucuronoxylomannan-protein conjugate vaccine in autoimmune and nonautoimmune mice.
The antibody response to Cryptococcus neoformans capsular glucuronoxylomannan (GXM) in BALB/c mice frequently expresses the 2H1 idiotype (Id) and is restricted in variable gene usage. This study examined the immunogenicity of GXM-protein conjugates, V (variable)-region usage, and 2H1 Id expression in seven mouse strains: BALB/c, C57BL/6, A/J, C3H, NZB, NZW, and (NZB x NZW)F(1) (NZB/W). All mouse strains responded to vaccination with GXM conjugated to tetanus toxoid (TT), the relative magnitude of the antibody response being BALB/c approximately C3H > C57BL/6 approximately NZB approximately NZW approximately NZB/W > A/J. Analysis of serum antibody responses to GXM with polyclonal and monoclonal antibodies to the 2H1 Id revealed significant inter- and intrastrain differences in idiotype expression. Thirteen monoclonal antibodies (MAbs) (two immunoglobulin M [IgM], three IgG3, one IgG1, three IgG2a, two IgG2b, and two IgA) to GXM were generated from one NZB/W mouse and one C3H/He mouse. The MAbs from the NZB/W mouse were all 2H1 Id positive (Id(+)) and structurally similar to those previously generated in BALB/c mice, including the usage of a V(H) from the 7183 family and Vkappa5.1. Administration of both 2H1 Id(+) and Id(-) MAbs from NZB/W and C3H/H3 mice prolonged survival in a mouse model of cryptococcosis. Our results demonstrate (i) that V-region restriction as indicated by the 2H1 Id is a feature of both primary and secondary responses of several mouse strains; and (ii) that there is conservation of V-region usage and length of the third complementarity-determining region in antibodies from three mouse strains. The results suggest that V-region restriction is a result of antibody structural requirements necessary for binding an immunodominant antigen in GXM.


Educating the community about the opioid epidemic and medications for opioid use disorder.
Despite overwhelming evidence of benefit, medications for opioid use disorder (MOUD) remain stigmatizing and more efforts are needed to educate health care professionals and the general public. We developed and evaluated an educational program for graduate students studying health sciences, teaching them to deliver 1 h presentations to the community on the opioid crisis and the usefulness of MOUD. To date, 120 graduate students have participated in this training experience on substance use disorders and delivered 59 presentations to more than 1065 community members. We found a significant increase in knowledge among students following the training. In addition, although attitudes and beliefs were generally positive at baseline, we also found significant increases in positives attitudes about the treatment of addiction and working with patients with addictions. Almost all students believed the course enhanced their professional expertise and would recommend it to others. We compared our students' baseline knowledge and attitudes to a large sample of other graduate students and did not find significant differences indicating good external validity of our results. Finally, we evaluated change in community members' knowledge and attitudes (N = 315) following student presentations and found significant increases in knowledge and positive attitude change toward MOUD. Overall our program was feasible, enjoyable, and effective in meeting its goals of increasing knowledge acquisition and improving attitudes among students and the greater community. Graduate students in health sciences can be trained to successfully teach the public about the opioid crisis and the usefulness of MOUD.


The INDEPTH (Impact of Nuclear Domains on Gene Expression and Plant Traits) Academy: a community resource for plant science.
This Community Resource paper introduces the range of materials developed by the INDEPTH (Impact of Nuclear Domains on Gene Expression and Plant Traits) COST Action made available through the INDEPTH Academy. Recent rapid growth in understanding of the significance of epigenetic controls in plant and crop science has led to a need for shared, high-quality resources, standardization of protocols, and repositories for open access data. The INDEPTH Academy provides a range of masterclass tutorials, standardized protocols, and teaching webinars, together with a rapidly developing repository to support imaging and spatial analysis of the nucleus and deep learning for automated analysis. These resources were developed partly as a response to the COVID-19 pandemic, but also driven by needs and opportunities identified by the INDEPTH community of ~200 researchers in 80 laboratories from 32 countries. This community report outlines the resources produced and how they will be extended beyond the INDEPTH project, but also aims to encourage the wider community to engage with epigenetics and nuclear structure by accessing these resources.


Speckled eggs: water-loss and incubation behaviour in the great tit Parus major.
Many small passerine birds worldwide lay white eggs speckled with red, brown and black protoporphyrin pigment spots (maculation). Unlike some patterns of avian eggshell pigmentation which clearly serve a crypsis or signalling function, the ubiquity of maculation among passerines suggests that its origins lie in another function, not specific to any particular ecological or behavioural group. Elsewhere, we have presented evidence that protoporphyrin pigments serve a structural function related to eggshell thickness and calcium availability: eggshell maculation in the great tit Parus major increases with decreasing soil calcium levels, pigments demarcate thinner areas of shell, and both the pigment intensity and distribution are related to shell thickness. Here we show that maculation also affects the rate of water loss from the egg during incubation (approximately Mass Loss per Day or MLD, which is critical to egg viability), but not that of unincubated eggs. We also demonstrate, both by observation and experiment, that the effect of female incubation behaviour on MLD compensates in some way for variation in egg characteristics, and that differences between females in the degree of such compensation are related to differences in clutch maculation. Our results suggest that, while a principal function of maculation in this species may be to strengthen the eggshell, it may also reduce eggshell permeability when large amounts of pigment are used, and that this necessitates a behavioural adjustment from the female during incubation. We discuss these findings and make further testable predictions from our model.


Effects of dietary conjugated linoleic acid and linoleic:linolenic acid ratio on polyunsaturated fatty acid status in laying hens.
A study was conducted to determine the effects of dietary conjugated linoleic acid (CLA) and the ratio of linoleic:linolenic acid on long-chain polyunsaturated fatty acid status. Thirty-two 31-wk-old White Leghorn hens were randomly assigned to four diets containing 8.2% soy oil, 4.1% soy oil + 2.5% CLA (4.1% CLA source), 4.1% flax oil + 2.5% CLA, or 4.1% soy oil + 4.1% flax oil. Hens were fed the diets for 3 wk before eggs and tissues were collected for the study. Lipids were extracted from egg yolk and tissues, classes of egg yolk lipids were separated, and fatty acid concentrations of total lipids, triglyceride, phosphatidylethanolamine, and phosphatidylcholine were analyzed by gas chromatography. The concentrations of monounsaturated fatty acids and non-CLA polyunsaturated fatty acids were reduced after CLA feeding. The amount of arachidonic acid was decreased after CLA feeding in linoleic acid- and linolenic acid-rich diets, but amounts of eicosapentaenoic acid and docosahexaenoic acid were increased in the linolenic-rich diet, indicating that the synthesis or deposition of long-chain n-3 fatty acids was accelerated after CLA feeding. The increased docosahexaenoic acid and eicosapentaenoic acid contents in lipid may be compensation for the decreased arachidonic acid content. Dietary supplementation of linoleic acid increased n-6 fatty acid levels in lipids, whereas linolenic acid increased n-3 fatty acid levels. Results also suggest that CLA might not be elongated to synthesize long-chain fatty acids in significant amounts. The effect of CLA in reducing the level of n-6 fatty acids and promoting the level of n-3 fatty acids could be related to the biological effects of CLA.


Neural correlates of the self-reference effect: evidence from evaluation and recognition processes.
The self-reference effect (SRE) is defined as better recall or recognition performance when the memorized materials refer to the self. Recently, a number of neuroimaging studies using self-referential and other-referential tasks have reported that self- and other-referential judgments basically show greater activation in common brain regions, specifically in the medial prefrontal cortex (MPFC) when compared with nonmentalizing judgments, but that a ventral-to-dorsal gradient in MPFC emerges from a direct comparison between self- and other-judgments. However, most of these previous studies could not provide an adequate explanation for the neural basis of SRE because they did not directly compare brain activation for recognition/recall of the words referenced to the self with another person. Here, we used an event-related functional magnetic resonance imaging (fMRI) that measured brain activity during processing of references to the self and another, and for recognition of self and other referenced words. Results from the fMRI evaluation task indicated greater activation in ventromedial prefrontal cortex (VMPFC) in the self-referential condition. While in the recognition task, VMPFC, posterior cingulate cortex (PCC) and bilateral angular gyrus (AG) showed greater activation when participants correctly recognized self-referenced words versus other-referenced words. These data provide evidence that the self-referenced words evoked greater activation in the self-related region (VMPFC) and memory-related regions (PCC and AG) relative to another person in the retrieval phase, and that the words remained as a stronger memory trace that supports recognition.


Effects of the metals on dihydropteridine reductase activity.
Metals are the oldest toxins known to human. Particularly, occupational and environmental exposure to aluminium, lead, mercury, cadmium, and manganese cause serious health problems by interaction with biological systems. Cellular targets of these metals are mostly specific biochemical processes (enzymes) and/or membranes of cells and organelles. To prevent and/or reduce the untoward or irreversible toxic effects of the metals by using biomarkers are as important as to know and to understand of their toxicity mechanisms. Dihydropteridine reductase (DHPR), which possessed essential thiol groups at the activity site, plays a crucial role in the maintenance of tetrahydrobiopterin (BH4). BH4 is the cofactor in the synthesis and regulation of neurotransmitters. A limited number of the evidences have shown that DHPR may be a target for the metals. Therefore, the present study was designed to assess possible in vitro effects of the commonly exposed metals on the enzyme activity. It was found that aluminium, cadmium, mercury, di-phenyl mercury, lead, diethyl lead, in chloride forms, and manganese, in sulphate form, led to statistically significant decreases in DHPR activity, in a concentration-dependent manner, in vitro.


Learning to not know: results of a program for ancillary cost reduction in surgical critical care.
Compelling internal and external influences are stimulating global re-evaluations of care standards for efficacy and cost. Critical care uses huge amounts of resources despite widespread shortages of beds and nurses. This study tested the hypothesis that ancillary expenditures can be decreased without compromising care. Costs for laboratory tests, radiographs, blood products, nutritional supplements, and drugs were compared prospectively for all surgical intensive care unit care for two 4-month periods (January 1 to April 30, 1994 and January 1 to April 30, 1995) at a urban university center. A systematic, multidisciplinary cost-reduction program began May 1, 1994, with emphasis on laboratory and radiographic testing and procedures, and blood product, nutritional, and drug therapies. Cohorts were compared by age, Acute Physiology and Chronic Health Evaluation (APACHE) II and III admission scores, and case mix. Outcome variables were hospital mortality, days in the intensive care unit and hospital, the development of multiple organ dysfunction syndrome, and expenditures. Cost data were taken weekly from the hospital's clinical information system. No new equipment was introduced during the study period except for pumps for patient-controlled analgesia, and there were no new critical pathways or other patient care guidelines. Case mix and all noncost variables were identical. Overall costs were reduced by 29% when normalized by the number of patient-days in each period. Laboratory testing was reduced in frequency by 24 to 32%, and cost by 26 to 28%. Comparable reductions in the cost of blood products (32%) were exceeded by the reductions in expenditures for nutritional supplements (49%) and pharmaceuticals (45%) (all, p < 0.01 or less). Modestly increased (2%) x-ray charges in 1995 were owing entirely to insertion of prophylactic inferior vena cava filters (each, $2,800, n = 5) and computed tomography scans for sinusitis (each, $350, n = 5), although the 7% reduction in portable chest radiographs that was achieved did not meet expectations. Substantial reductions in physician-ordered ancillary expenditures are possible without compromising the standard of care of critically ill patients, or the support of an elaborate framework of defined care plans. With additional experience, incremental savings may accrue from refinement of successful strategies and new approaches to intractable problems.


Livestock ownership and anaemia in Sub-Saharan African households.
To determine the association between livestock ownership and Hb concentration of women of child-bearing age (WCBA) and preschool-aged children in Sub-Saharan Africa (SSA). A prospective analysis of publicly available cross-sectional data, using linear and logistic regressions controlling for potential confounders. Twenty-eight countries in SSA. 162 305 WCBA and 118 607 children aged 6-59 months. More than half of WCBA (62·5 %) and children (58 %) belonged to households that owned livestock. The average altitude-adjusted blood Hb concentration for WCBA and children was 12.23 and 10·24 g/dL, respectively. In adjusted models, higher number of livestock owned was associated with lower Hb concentration for children but not for WCBA. The magnitude of the association for children was small, with one additional unit of livestock owned reducing Hb concentration by 0·001 g/dL. Higher numbers of cattle, cows and bulls, sheep, and goats were associated with lower Hb concentration for both groups. The number of certain categories of livestock owned was associated with the consumption of relevant foods by children. There was no association between the consumption of animal-source foods and Hb concentration or between livestock ownership and diarrhoeal diseases or fever among children. Livestock ownership in SSA had a net negative association with the Hb concentration of children and no association with that of WCBA. The results highlight the need for research aimed at clarifying the mechanisms linking livestock ownership and nutritional status, and identifying entry points for leveraging livestock ownership to improve the health of women and children in SSA.


Adsorption of chitosan on PET films monitored by quartz crystal microbalance.
The adsorption behavior of chitosan on poly(ethylene terephthalate) (PET) model film surface was studied using the quartz crystal microbalance (QCM) technique. QCM with a dissipation unit (QCM-D) represents a very sensitive technique for adsorption studies at the solid/liquid interface in situ, with capability of detecting a submonolayer of adsorbate on the quartz crystal surface. Chitosan as well as PET were chosen for this study due to their promising biocompatible properties and numerous possibilities to be used in biomedical applications. As a first step, PET foils were activated by alkaline hydrolysis in order to increase their hydrophilicity. Model thin films were prepared from PET foils by the spin coating technique. The chemical composition of the obtained model PET films was analyzed using X-ray photoelectron spectroscopy (XPS) and their morphology was characterized by atomic force microscopy (AFM). Furthermore, the adsorption behavior of chitosan on these activated PET films and the influence of adsorption parameters (pH, ionic strength and chitosan solution concentration) were investigated in detail. Additionally, the surface chemistry and morphology of the PET films and the chitosan coated PET films were analyzed with XPS and AFM.


Influence of Cu nanoparticle size on the photo-electrochemical response from Cu-multiwall carbon nanotube composites.
We show that Cu metal nanoparticle-multiwall carbon nanotube (MWCNT) assemblies can act as a new hybrid photoactive layer in photo-electrochemical devices. The carbon nanotube (CNT) composites were formed by a controlled thermal deposition of copper which produced crystalline metal nanoparticles localized on the carbon tube outer walls. The photoresponse evaluated in terms of IPCE (incident photon-to-charge carrier generation efficiency) varied for different sized-Cu-MWCNT samples across all the visible and near ultraviolet photon energy range with respect to the response of bare MWCNTs. In the case of 0.2 nm Cu nominal thickness, the IPCE increased, reaching 15%, a value 2.5 times higher than that measured for bare MWCNTs. As the Cu nominal coverage thickened, the IPCE started to decrease and become totally ineffective after 1 nm deposited Cu. The IPCE increase found was interpreted as being the result of a remarkable charge transfer between the Cu metal nanoparticles and the CNTs due to the formation of a strong ionic bond at their interface. The results obtained prove that the metal nanoparticle-CNT composites have optical, electrical and structural properties that can be applied in a variety of nanoscale architectures for novel photo-electrochemical devices.


Preoperative assessment of the older patient: a narrative review.
Surgery in older patients often poses risks of death, complications, and functional decline. Prior to surgery, evaluations of health-related priorities, realistic assessments of surgical risks, and individualized optimization strategies are essential. To review surgical decision making for older adult patients by 2 measures: defining treatment goals for elderly patients and reviewing the evidence relating risk factors to adverse outcomes. Assessment and optimization strategies for older surgical patients are proposed. A review of studies relating geriatric conditions such as functional and cognitive impairment, malnutrition, facility residence, and frailty to postoperative mortality and complications (including delirium, discharge to an institution, and functional decline). Medline, EMBASE, and Web of Science databases were searched for articles published between January 1, 2000, and December 31, 2013, that included patients older than 60 years. This review identified 54 studies of older patients; 28 that examined preoperative clinical features associated with mortality (n = 1,422,433 patients) and 26 that examined factors associated with surgical complications (n = 136,083 patients). There was substantial heterogeneity in study methods, measures, and outcomes. The absolute risk and risk ratios relating preoperative clinical conditions to mortality varied widely: 10% to 40% for cognitive impairment (adjusted hazard ratio [HR], 1.26 [95% CI, 1.06-1.49] to 5.77 [95% CI, 1.55-21.55]), 10% to 17% for malnutrition (adjusted odds ratio [OR], 0.88 [95% CI, 0.78-1.01] to 59.2 [95% CI, 3.6-982.9]), and 11% to 41% for institutionalization (adjusted OR, 1.5 [95% CI, 1.02-2.21] to 3.27 [95% CI, 2.81-3.81]).) Risk ratios for functional dependence relating to mortality ranged from an adjusted HR of 1.02 (95% CI, 0.99-1.04) to an adjusted OR of 18.7 (95% CI, 1.6-215.3) and for frailty relating to mortality, ranged from an adjusted HR of 1.10 (95% CI, 1.04-1.16) to an adjusted OR of 11.7 (95% CI not reported) (P < .001). Preoperative cognitive impairment (adjusted OR, 2.2; 95% CI, 1.4-2.7) was associated with postoperative delirium (adjusted OR, 17.0; 95% CI, 1.2-239.8; P < .05). Frailty was associated with a 3- to 13-fold increased risk of discharge to a facility (adjusted OR, 3.16 [95% CI, 1.0-9.99] to 13.02 [95% CI, 5.14-32.98]). Geriatric conditions may be associated with adverse surgical outcomes. A comprehensive evaluation of treatment goals and communication of realistic risk estimates are essential to guide individualized decision making.


Metabolic syndrome and adipose tissue: new clinical aspects and therapeutic targets.
The metabolic syndrome is a long-term process, explained by the interaction of genetic and environmental factors, that starts early in life and is involved in the pathophysiology of a large percentage of cases with type 2 diabetes and atherosclerosis. A number of clinical studies have demonstrated the importance of fat distribution and especially the contribution of visceral fat accumulation to the development of metabolic disorders. Visceral adipose tissue can be studied through different imaging techniques. The accumulation of visceral adipose tissue, as opposed to subcutaneous fat, increases the risk of developing metabolic disease and cardiovascular diseases (CVD). Visceral adipocytes secrete a variety of cytokines known as adipocytokines suggesting that adipose tissue is an endocrine organ that may affect the function of other organs. Weight loss, particularly a reduction in waist circumference, improves insulin sensitivity, lipid profile, and serum adipocytokines, reducing the risk of developing chronic disease and CVD. Waist circumference is a required component of metabolic syndrome under the International Diabetes Federation (IDF) criteria, rather than an optional component as used by other previous classifications. Studies have shown that using a lower waist circumference threshold within the context of metabolic syndrome increases the prevalence, but decreases the risk of mortality and type 2 diabetes. It is possible that waist circumference acts as a marker for other risk factors. These findings reinforce the notion that reductions in visceral adipose tissue should be a primary aim of strategies designed to reduce health risks associated with metabolic syndrome.


Terrestrial dissolved organic matter inputs drive the temporal dynamics of riverine bacterial ecological networks and assembly processes.
Rivers receive, transport, and are reactors of terrestrial dissolved organic matter (DOM) and are highly influenced by changes in hydrological conditions and anthropogenic disturbances, but the effect of DOM composition on the dynamics of the bacterial community in rivers is poorly understood. We conducted a seasonal field sampling campaign at two eutrophic river mouth sites to examine how DOM composition influences the temporal dynamics of bacterial community networks, assembly processes, and DOM-bacteria associations. DOM composition and seasonal factors explained 34.7% of the variation in bacterial community composition, and 14.4% was explained purely by DOM composition where specific UV absorbance (SUVA254) as an indicator of aromaticity was the most important predictor. Significant correlations were observed between SUVA254 and the topological features of subnetworks of interspecies and DOM-bacteria associations, indicating that high DOM aromaticity results in more complex and connected networks of bacteria. The bipartite networks between bacterial taxa and DOM molecular formulae (identified by ultrahigh-resolution mass spectrometry) further revealed less specialized bacterial processing of DOM molecular formulae under the conditions of high water level and DOM aromaticity in summer than in winter. A shift in community assembly processes from stronger homogeneous selection in summer to higher stochasticity in winter correlated with changes in DOM composition, and more aromatic DOM was associated with greater similarity in bacterial community composition. Our results highlight the importance of DOM aromaticity as a predictor of the temporal dynamics of riverine bacterial community networks and assembly.


Rationally designed ruthenium complexes for 1- and 2-photon photodynamic therapy.
The use of photodynamic therapy (PDT) against cancer has received increasing attention over recent years. However, the application of the currently approved photosensitizers (PSs) is limited by their poor aqueous solubility, aggregation, photobleaching and slow clearance from the body. To overcome these limitations, there is a need for the development of new classes of PSs with ruthenium(II) polypyridine complexes currently gaining momentum. However, these compounds generally lack significant absorption in the biological spectral window, limiting their application to treat deep-seated or large tumors. To overcome this drawback, ruthenium(II) polypyridine complexes designed in silico with (E,E')-4,4'-bisstyryl-2,2'-bipyridine ligands show impressive 1- and 2-Photon absorption up to a magnitude higher than the ones published so far. While nontoxic in the dark, these compounds are phototoxic in various 2D monolayer cells, 3D multicellular tumor spheroids and are able to eradicate a multiresistant tumor inside a mouse model upon clinically relevant 1-Photon and 2-Photon excitation.


The psychometric characteristics of the revised depression attitude questionnaire (R-DAQ) in Pakistani medical practitioners: a cross-sectional study of doctors in Lahore.
Depression is common mental health problem and leading contributor to the global burden of disease. The attitudes and beliefs of the public and of health professionals influence social acceptance and affect the esteem and help-seeking of people experiencing mental health problems. The attitudes of clinicians are particularly relevant to their role in accurately recognising and providing appropriate support and management of depression. This study examines the characteristics of the revised depression attitude questionnaire (R-DAQ) with doctors working in healthcare settings in Lahore, Pakistan. A cross-sectional survey was conducted in 2015 using the revised depression attitude questionnaire (R-DAQ). A convenience sample of 700 medical practitioners based in six hospitals in Lahore was approached to participate in the survey. The R-DAQ structure was examined using Parallel Analysis from polychoric correlations. Unweighted least squares analysis (ULSA) was used for factor extraction. Model fit was estimated using goodness-of-fit indices and the root mean square of standardized residuals (RMSR), and internal consistency reliability for the overall scale and subscales was assessed using reliability estimates based on Mislevy and Bock (BILOG 3 Item analysis and test scoring with binary logistic models. Mooresville: Scientific Software, 55) and the McDonald's Omega statistic. Findings using this approach were compared with principal axis factor analysis based on Pearson correlation matrix. 601 (86%) of the doctors approached consented to participate in the study. Exploratory factor analysis of R-DAQ scale responses demonstrated the same 3-factor structure as in the UK development study, though analyses indicated removal of 7 of the 22 items because of weak loading or poor model fit. The 3 factor solution accounted for 49.8% of the common variance. Scale reliability and internal consistency were adequate: total scale standardised alpha was 0.694; subscale reliability for professional confidence was 0.732, therapeutic optimism/pessimism was 0.638, and generalist perspective was 0.769. The R-DAQ was developed with a predominantly UK-based sample of health professionals. This study indicates that this scale functions adequately and provides a valid measure of depression attitudes for medical practitioners in Pakistan, with the same factor structure as in the scale development sample. However, optimal scale function necessitated removal of several items, with a 15-item scale enabling the most parsimonious factor solution for this population.


Bottlenose dolphins engaging in more social affiliative behaviour judge ambiguous cues more optimistically.
Cognitive bias tests measure variation in emotional appraisal and are validated methods to assess animals' affective states. However, the link between social behaviours and cognitive bias has not yet been investigated. Bottlenose dolphins are a gregarious species for whom welfare research is increasing in importance, and thus are a good model to test such an association. We adapted a spatial location judgement bias test for eight captive bottlenose dolphins to investigate the link between cognitive bias and social behaviour, where we conducted behavioural observations outside of training sessions and did not experimentally induce an affective state. Subjects showed stable individual differences in cognitive biases across the three test days. Furthermore, dolphins showing more synchronous swimming, a fundamental affiliative behaviour, judged ambiguous cues significantly more optimistically. Our longer-term data showed cognitive bias and synchronous swimming frequency were significantly associated for up to two months preceding the test, but disappeared prior to that, suggesting that here cognitive bias differences were reflected by transitory affective states rather than longer-term traits. We hypothesise that the frequency of synchronous swimming may induce affective states and/or be induced by them; either way, it has strong potential as an indicator of affective state in this species and beyond.


Reversible hydrogel-solution system of silk with high beta-sheet content.
Silkworm silk has been widely used as a textile fiber, as biomaterials and in optically functional materials due to its extraordinary properties. The β-sheet-rich natural nanofiber units of about 10-50 nm in diameter are often considered the origin of these properties, yet it remains unclear how silk self-assembles into these hierarchical structures. A new system composed of β-sheet-rich silk nanofibers about 10-20 nm in diameter is reported here, where these nanofibers formed into "flowing hydrogels" at 0.5-2% solutions and could be transformed back into the solution state at lower concentrations, even with a high β-sheet content. This is in contrast with other silk processed materials, where significant β-sheet content negates reversibility between solution and solid states. These fibers are formed by regulating the self-assembly process of silk in aqueous solution, which changes the distribution of negative charges while still supporting β-sheet formation in the structures. Mechanistically, there appears to be a shift toward negative charges along the outside of the silk nanofibers in our present study, resulting in a higher zeta potential (above -50 mV) than previous silk materials which tend to be below -30 mV. The higher negative charge on silk nanofibers resulted in electrostatic repulsion strong enough to negate further assembly of the nanofibers. Changing silk concentration changed the balance between hydrophobic interactions and electrostatic repulsion of β-sheet-rich silk nanofibers, resulting in reversible hydrogel-solution transitions. Furthermore, the silk nanofibers could be disassembled into shorter fibers and even nanoparticles upon ultrasonic treatment following the transition from hydrogel to solution due to the increased dispersion of hydrophobic smaller particles, without the loss of β-sheet content, and with retention of the ability to transition between hydrogel and solution states through reversion to longer nanofibers during self-assembly. These reversible solution-hydrogel transitions were tunable with ultrasonic intensity, time, or temperature.


[Representations of aging for community health agents and nursing professionals: psychological aspects of the health-disease process].
This paper addresses the aging process in the context of public health, with emphasis to human resources and to how aging is perceived by the public health professionals. The aim of this study was to identify the representations of the aging process for public health professionals and how these representations are expressed in health care, well-being and elderly care. The sample included 27 public health professionals, 10 community health agents and 17 nursing professionals. Two instruments were used, a sociocultural questionnaire and a questionnaire about aging representations. Data analysis included qualitative and quantitative procedures (Chi-square test). Among the main findings, the most representative words used in relation to aging were retirement and rest. For this sample, good family support and care were considered the most important factors contributing to the well-being of the elderly. When it comes to defining care, the most frequent concept referred to biological aspects. Moreover, this sample in general showed some knowledge about Alzheimer Disease. These findings can contribute to the capacitation of human resources. Health agents and nursing professionals should be guided towards construction of a deeper comprehension of the biopsychosocial context of the aging process.


Thermodynamic investigation of the adsorption of amides on graphite from their liquids and binary mixtures.
We report a thermodynamic investigation of the adsorption of saturated and unsaturated (cis- and trans-) alkyl amides onto the surface of graphite from their pure liquids and from binary mixtures. We identify the formation of solid monolayers of the amides at temperatures when the bulk materials are liquid. The extent of this presolidification is much more extensive than other related materials, indicating that these amide layers are significantly more stable. The monolayer stability is found to be greatest for saturated amides. In addition, the stability of unsaturated amides is extremely sensitive to the location of the double bonds in the alkyl chain of the molecules, and trans isomers are found to be more stable than cis. We also address the preferential adsorption and mixing behavior of amide mixtures and amides mixed with other species coadsorbed onto graphite from binary solution. The results indicate that the amide molecules appear to be adsorbed with their principal axis parallel to the graphite surface and that amides are found to be strongly preferentially adsorbed with respect to alkanes. Interestingly the amides appear to mix rather better than might have been expected. There is also evidence of a number of other transitions in the adsorbates.


Diffusion tensor imaging of the visual pathway in dogs with primary angle-closure glaucoma.
To describe measurements of in vivo structures of the visual pathway beyond the retina and optic nerve head associated with canine primary angle-closure glaucoma (PACG). A prospective pilot study was conducted using magnetic resonance diffusion tensor imaging (DTI) to obtain quantitative measures of the optic nerve, chiasm, tract, and lateral geniculate nucleus (LGN) in dogs with and without PACG. 3-Tesla DTI was performed on six affected dogs and five breed, age- and sex-matched controls. DTI indices of the optic nerve, optic chiasm, optic tracts, and LGN were compared between normal, unilateral PACG, and bilateral PACG groups. Intra-class correlation coefficient (ICC) was calculated to assess intra-observer reliability. Quantitative measurements of the optic nerve, optic tract, optic chiasm, and LGN were obtained in all dogs. There was a trend for reduced fractional anisotropy (FA) associated with disease for all structures assessed. Compared to the same structure in normal dogs, FA, and radial diffusivity (RD) of the optic nerve was consistently higher in the unaffected eye in dogs with unilateral PACG. Intra-observer reliability was excellent for measurements of the optic nerve (ICC: 0.92), good for measurements of the optic tract (ICC: 0.89) and acceptable for measures of the optic chiasm (ICC: 0.71) and lateral geniculate nuclei (ICC: 0.76). Diffusivity and anisotropy measures provide a quantifiable means to evaluate the visual pathway in dogs. DTI has potential to provide in vivo measures of axonal and myelin injury and transsynaptic degeneration in canine PACG.


Topological kagome magnets and superconductors.
A kagome lattice naturally features Dirac fermions, flat bands and van Hove singularities in its electronic structure. The Dirac fermions encode topology, flat bands favour correlated phenomena such as magnetism, and van Hove singularities can lead to instabilities towards long-range many-body orders, altogether allowing for the realization and discovery of a series of topological kagome magnets and superconductors with exotic properties. Recent progress in exploring kagome materials has revealed rich emergent phenomena resulting from the quantum interactions between geometry, topology, spin and correlation. Here we review these key developments in this field, starting from the fundamental concepts of a kagome lattice, to the realizations of Chern and Weyl topological magnetism, to various flat-band many-body correlations, and then to the puzzles of unconventional charge-density waves and superconductivity. We highlight the connection between theoretical ideas and experimental observations, and the bond between quantum interactions within kagome magnets and kagome superconductors, as well as their relation to the concepts in topological insulators, topological superconductors, Weyl semimetals and high-temperature superconductors. These developments broadly bridge topological quantum physics and correlated many-body physics in a wide range of bulk materials and substantially advance the frontier of topological quantum matter.


Selective growth in serum-free hormone-supplemented medium of tumor cells obtained by biopsy from patients with small cell carcinoma of the lung.
Fifteen tumor-containing specimens were obtained directly from patients with small cell carcinoma of the lung and tested for their ability to grow in serum-supplemented medium and in serum-free medium supplemented with hydrocortisone, insulin, transferrin, estrogen, and selenium (HITES). The tumor cells replicated in 14 of 15 cases (93%) in the HITES medium and in 10 of 15 cases (67%) in the serum-supplemented medium. The neoplastic origin of the cells growing in the HITES medium was confirmed by standard cytologic criteria, by DNA content analysis using flow cytometry, and by their ability to form colonies in agarose and tumors in athymic nude mice. While the tumor cells had very similar morphologies in both media, the serum-free medium did not support the growth of nonmalignant stromal cells, and essentially pure cultures of replicating tumor cells were obtained 7-10 days after plating. The selectivity of the HITES medium was demonstrated by the failure of cells to grow in 20 specimens cytologically negative for small cell carcinoma and in 9 of 10 specimens containing other tumor types (including other types of lung cancer). The results demonstrate that a chemically defined medium, determined by work on tissue culture-adapted human tumor lines, can support the selective growth of tumor specimens obtained directly from patients. Such selective formulas are probably specific for different tumor types and thus could be used for diagnosis, drug sensitivity testing in vitro, and identification of factors regulating tumor growth. All of these have direct application to patient treatment.


Risk of using hydroxychloroquine as a treatment of COVID-19.
The emerging COVID-19 pandemic poses a threat to the global health care system. Given the lack of antiviral therapies or vaccines for the disease, the antimalarial drug hydroxychloroquine (HCQ) obtained much attention as a treatment for COVID-19. However, there are limited and uncertain clinical data to support the beneficial effect of this drug in COVID-19 treatment. HCQ has several side effects and warnings, including blindness, heart failure, and renal toxicity, even with recommended doses. For severe cases of COVID-19 or in patients with preexisting conditions, administering such a drug could be fatal, particularly when taken at high doses or in combination with other antibiotics. However, further well-designed studies that would address the optimal dose, duration of treatment, possible side effects, and long-term usage outcomes are needed to make the final decision. In this paper, we aim to discuss the risk of using HCQ in treating COVID-19 patients, including its possible side effects.


Subthalamic nucleus stimulation in patients with a prior pallidotomy.
A substantial number of patients with Parkinson disease (PD) who have undergone unilateral stereotactic pallidotomy ultimately develop symptom progression, becoming potential candidates for further surgical treatment. Bilateral subthalamic nucleus (STN) deep brain stimulation (DBS) has been shown to be effective in the treatment of a subset of patients with refractory PD. Microelectrode recording is performed to help localize the STN and guide final placement of the electrode. Potential alterations in physiological features of the STN after pallidotomy may complicate localization of this structure in this group of patients. Bilateral STN DBS surgery guided by microelectrode recording was performed in six patients who had undergone previous unilateral pallidotomies. Physiologically obtained parameters of the STN, including trajectory length, mean firing rate, cell number, and cell density were calculated. These data were compared with those from the side without prior pallidotomy within each patient, as well as with those from our series of 49 subthalamic nuclei explored in 26 patients who had not undergone prior pallidotomy but who underwent bilateral STN stimulator placement. In all patients, analysis of STN cellular activity on the side ipsilateral to the pallidotomy demonstrated a lower mean firing frequency than on the contralateral, intact side. The physiological features on the intact side were not significantly different from those found in our series of patients who had not undergone prior pallidotomy. Physicians who perform STN surgery in patients with prior pallidotomy should be aware of the electrophysiological differences between the STN that had undergone pallidotomy and the one that had not, to avoid prolonging recording time to search for the typical STN. The implications of these findings for the current models of information processing in the basal ganglia are discussed.


Hepatic steatosis and insulin resistance are associated with severe fibrosis in patients with chronic hepatitis caused by HBV or HCV infection.
Steatosis and insulin resistance (IR) are the major disease modifying in patients with chronic hepatitis C (CHC). Only few studies evaluated these features in patients with chronic hepatitis B (CHB). We aimed to assess the prevalence and the factors related to steatosis and IR in CHB patients, compared with CHC subjects, and to evaluate the potential association between these features and fibrosis severity. One hundred and seventy consecutive patients with CHB (28 HBeAg positive, 142 HBeAg negative), were evaluated using liver biopsy and metabolic measurements and matched for sex, age and body mass index with 170 genotype 1 CHC patients. IR was defined if HOMA-IR>2.7. All biopsies were scored for grading and staging by Scheuer's score, and the steatosis was considered significant if ≥ 10%. The prevalence of significant steatosis was similar in both CHB and CHC patients (31 vs. 38%; P=0.14). IR rate was significantly higher in CHC than in CHB patients (42 vs. 26%; P=0.002). Severe fibrosis (F3-F4), at multivariate analysis, was independently associated with older age (OR 1.050, 95% CI 1.009-1.093), steatosis >10% (OR 4.375, 95% CI 1.749-10.943), and moderate-severe necroinflammatory activity (OR 8.187, 95% CI 2.103-31.875), regardless of HBeAg status, in CHB patients, and with older age (OR 1.080, 95% CI 1.028-1.136), IR (OR 2.640, 95% CI 1.110-6.281), steatosis >10% (OR 3.375, 95% CI 1.394-8.171), and moderate-severe necroinflammatory activity (OR 8.988, 95% CI 1.853-43.593) in CHC patients. CHB patients had high steatosis prevalence, similar to CHC controls, but lower IR rate. Both steatosis and IR in CHC, and only steatosis in CHB, are independently associated with fibrosis severity.


Ecology, Worldwide Spread, and Management of the Invasive South American Tomato Pinworm, Tuta absoluta: Past, Present, and Future.
The South American tomato pinworm, Tuta absoluta (Meyrick), is native to the western Neotropics. After invading Spain in 2006, it spread rapidly throughout Afro-Eurasia and has become a major threat to world tomato production. Integrated pest management (IPM) strategies have been developed, but widespread insecticide use has caused selection for insecticide resistance as well as undesirable effects on key beneficial arthropods. Augmentation and conservation biological control relying on omnivorous mirid predators has proved successful for management of T. absoluta, where implementation is dependent on abiotic, biotic (e.g., alternative prey), and anthropogenic factors (e.g., pesticides). Research has been carried out on larval parasitoids, showing potential for further development of sustainable control. The development of resistant tomato varieties is ongoing, but they are not commercially available yet. Knowledge gaps remain to be filled to optimize IPM packages on tomato crops and to help prevent further spread worldwide.


Inositols in the ovaries: activities and potential therapeutic applications.
Myo-inositol (MI) and d-chiro-inositol (DCI) play a key role in ovarian physiology, as they are second messengers of insulin and gonadotropins. Ex-vivo and in-vitro experiments demonstrate that both isomers are deeply involved in steroid biosynthesis, and that reduced MI-to-DCI ratios are associated with pathological imbalance of sex hormones. This expert opinion provides an overview of the physiological distribution of MI and DCI in the ovarian tissues, and a thorough insight of their involvement into ovarian steroidogenesis. Insulin resistance and compensatory hyperinsulinemia dramatically reduce the MI-to-DCI ratio in the ovaries, leading to gynecological disorders characterized by hyperandrogenism, altered menstrual cycle and infertility. Available evidence indicates that MI and DCI have very specific physiological roles and, seemingly, physiological MI-to-DCI ratios in the ovaries are crucial to maintain the correct homeostasis of steroids. Inositol treatments should be evaluated on the patients' specific conditions and needs, as long-term supplementation of high doses of DCI may cause detrimental effects on the ovarian functionality. In addition, the effects of inositol therapy on the different PCOS phenotypes should be further investigated in order to better tailor the supplementation.


Anti-SARS-CoV-2 IgG and IgA antibodies in COVID-19 convalescent plasma do not facilitate antibody-dependent enhance of viral infection.
The novel coronavirus SARS-CoV2, which causes COVID-19, has resulted in the death of nearly 4 million people within the last 18 months. While preventive vaccination and monoclonal antibody therapies have been rapidly developed and deployed, early in the pandemic the use of COVID-19 convalescent plasma (CCP) was a common means of passive immunization, with the theoretical risk of antibody-dependent enhancement (ADE) of viral infection remaining undetermined. Though vaccines elicit a strong and protective immune response, and transfusion of CCP with high titers of neutralization activity are correlated with better clinical outcomes, the question of whether antibodies in CCP can enhance infection of SARS-CoV2 has not been directly addressed. In this study, we analyzed for and observed passive transfer of neutralization activity with CCP transfusion. Furthermore, to specifically understand if antibodies against the spike protein (S) enhance infection, we measured the anti-S IgG, IgA, and IgM responses and adapted retroviral-pseudotypes to measure virus neutralization with target cells expressing the ACE2 virus receptor and the Fc alpha receptor (FcαR) or Fc gamma receptor IIA (FcγRIIA). Whereas neutralizing activity of CCP correlated best with higher titers of anti-S IgG antibodies, the neutralizing titer was not affected when Fc receptors were present on target cells. These observations support the absence of antibody-dependent enhancement of infection (ADE) by IgG and IgA isotypes found in CCP. The results presented, therefore, support the clinical use of currently available antibody-based treatment including the continued study of CCP transfusion strategies.


Improving the health of people with intellectual disabilities: outcomes of a health screening programme after 1 year.
People with intellectual disabilities (IDs) have a higher level of health needs, a higher level of which is unmet, compared with the general population. Health screening can detect unmet health needs, but it is unknown whether it effects beneficial health outcomes in the longer term. People with IDs are reliant on health management by proxy and there are many potential access barriers that may prevent health needs identified at screening from subsequently being met. This study aims to determine whether health gains can be detected 1 year after a health screening programme specific to the needs of adults with IDs. A total of 50 participants offered the health screen intervention were individually matched for gender, age and level of IDs with 50 control participants who received standard treatment only. Outcome measures after 1 year were semi-structured review of medical case notes, and semi-structured assessment with the people with IDs and their carer. During the 1-year period, the incidence of health need detection was more than twice as great for intervention, compared with control participants (mean number of new needs was 4.80 compared with 2.26; P < 0.001), and the level of met new health needs was greater (mean of 3.56 compared with 2.26; P = 0.001). The level of met health promotion needs was also greater (P < 0.001), and more health monitoring needs were met for intervention compared with control participants (P = 0.039). This is the first study to demonstrate sustained benefits in health outcomes from a clinical intervention for adults with IDs compared with standard treatment alone. Its routine implementation is feasible, and would reduce health inequalities.


Medial Amygdala Kiss1 Neurons Mediate Female Pheromone Stimulation of Luteinizing Hormone in Male Mice.
The medial amygdala (MeA) responds to olfactory stimuli and alters reproductive physiology. However, the neuronal circuit that relays signals from the MeA to the reproductive axis remains poorly defined. This study aimed to test whether MeA kisspeptin (MeAKiss) neurons in male mice are sensitive to sexually relevant olfactory stimuli and transmit signals to alter reproductive physiology. We also investigated whether MeAKiss neurons have the capacity to elaborate glutamate and GABA neurotransmitters and potentially contribute to reproductive axis regulation. Using female urine as a pheromone stimulus, MeAKiss neuronal activity was analysed and serum luteinizing hormone (LH) was measured in male mice. Next, using a chemogenetic approach, MeAKiss neurons were bi-directionally modulated to measure the effect on serum LH and evaluate the activation of the preoptic area. Lastly, using in situ hybridization, we identified the proportion of MeAKiss neurons that express markers for GABAergic (Vgat) and glutamatergic (Vglut2) neurotransmission. Male mice exposed to female urine showed a two-fold increase in the number of c-Fos-positive MeAKiss neurons concomitant with raised LH. Chemogenetic activation of MeAKiss neurons significantly increased LH in the absence of urine exposure, whereas inhibition of MeAKiss neurons did not alter LH. In situ hybridization revealed that MeAKiss neurons are a mixed neuronal population in which 71% express Vgat mRNA, 29% express Vglut2 mRNA, and 6% express both. Our results uncover, for the first time, that MeAKiss neurons process sexually relevant olfactory signals to influence reproductive hormone levels in male mice, likely through a complex interplay of neuropeptide and neurotransmitter signalling.


Polymerase chain reaction assay for avian polyomavirus.
A polymerase chain reaction assay was developed for detection of budgerigar fledgling disease virus (BFDV). The assay used a single set of primers complementary to sequences located in the putative coding region for the BFDV VP1 gene. The observed amplification product had the expected size of 550 bp and was confirmed to derive from BFDV DNA by its restriction digestion pattern. This assay was specific for BFDV and highly sensitive, being able to detect as few as 20 copies of the virus. By using the polymerase chain reaction, BFDV was detected in adult, nestling, and embryo budgerigar (Melopsitticus undulatus) tissue DNAs and in sera from adult and nestling budgerigars. These results suggest the possibility of persistent infections in adult birds and lend further support to previously described evidence of possible in ovo transmission. BFDV was also detected in chicken embryo fibroblast cell cultures and chicken eggs inoculated with the virus. A 550-bp product with identical restriction enzyme sites was amplified from a suspected polyomavirus isolated from a peach-faced lovebird (Agapornis pesonata) and from tissue DNA from a Hahn's macaw (Ara nobilis) and a sun conure (Aratinga solstitialis) with histological lesions suggestive of polyomavirus infection. These fragments also hybridized with a BFDV-derived probe, proving that they were derived from a polyomavirus very similar, if not identical, to BFDV.


Feeding Ecology of Northeast Atlantic Mackerel, Norwegian Spring-Spawning Herring and Blue Whiting in the Norwegian Sea.
The Norwegian spring-spawning (NSS) herring (Clupea harengus), blue whiting (Micromesistius poutassou) and Northeast Atlantic (NEA) mackerel (Scomber scombrus) are extremely abundant pelagic planktivores that feed in the Norwegian Sea (NS) during spring and summer. This study investigated the feeding ecology and diet composition of these commercially important fish stocks on the basis of biological data, including an extensive set of stomach samples in combination with hydrographical data, zooplankton samples and acoustic abundance data from 12 stock monitoring surveys carried out in 2005-2010. Mackerel were absent during the spring, but had generally high feeding overlap with herring in the summer, with a diet mainly based on calanoid copepods, especially Calanus finmarchicus, as well as a similar diet width. Stomach fullness in herring diminished from spring to summer and feeding incidence was lower than that of mackerel in summer. However, stomach fullness did not differ between the two species, indicating that herring maintain an equally efficient pattern of feeding as mackerel in summer, but on a diet that is less dominated by copepods and is more reliant on larger prey. Blue whiting tended to have a low dietary overlap with mackerel and herring, with larger prey such as euphausiids and amphipods dominating, and stomach fullness and feeding incidence increasing with length. For all the species, feeding incidence increased with decreasing temperature, and for mackerel so did stomach fullness, indicating that feeding activity is highest in areas associated with colder water masses. Significant annual effects on diet composition and feeding-related variables suggested that the three species are able to adapt to different food and environmental conditions. These annual effects are likely to have an important impact on the predation pressure on different plankton groups and the carrying capacity of individual systems, and emphasise the importance of regular monitoring of pelagic fish diets.


Molecular signatures in post-mortem brain tissue of younger individuals at high risk for Alzheimer's disease as based on APOE genotype.
Alzheimer's disease (AD) is a neurodegenerative condition characterized histopathologically by neuritic plaques and neurofibrillary tangles. The objective of this transcriptional profiling study was to identify both neurosusceptibility and intrinsic neuroprotective factors at the molecular level, not confounded by the downstream consequences of pathology. We thus studied post-mortem cortical tissue in 28 cases that were non-APOE4 carriers (called the APOE3 group) and 13 cases that were APOE4 carriers. As APOE genotype is the major genetic risk factor for late-onset AD, the former group was at low risk for development of the disease and the latter group was at high risk for the disease. Mean age at death was 42 years and none of the brains had histopathology diagnostic of AD at the time of death. We first derived interregional difference scores in expression between cortical tissue from a region relatively invulnerable to AD (primary somatosensory cortex, BA 1/2/3) and an area known to be susceptible to AD pathology (middle temporal gyrus, BA 21). We then contrasted the magnitude of these interregional differences in between-group comparisons of the APOE3 (low risk) and APOE4 (high risk) genotype groups. We identified 70 transcripts that differed significantly between the groups. These included EGFR, CNTFR, CASP6, GRIA2, CTNNB1, FKBPL, LGALS1 and PSMC5. Using real-time quantitative PCR, we validated these findings. In addition, we found regional differences in the expression of APOE itself. We also identified multiple Kyoto pathways that were disrupted in the APOE4 group, including those involved in mitochondrial function, calcium regulation and cell-cycle reentry. To determine the functional significance of our transcriptional findings, we used bioinformatics pathway analyses to demonstrate that the molecules listed above comprised a network of connections with each other, APOE, and APP and MAPT. Overall, our results indicated that the abnormalities that we observed in single transcripts and in signaling pathways were not the consequences of diagnostic plaque and tangle pathology, but preceded it and thus may be a causative link in the long molecular prodrome that results in clinical AD.


DETECTION OF SPECIFIC ANTIGEN IN SV40-TRANSFORMED CELLS BY IMMUNOFLUORESCENCE.
With an immunofluorescent technique involving the use of serum of hamsters with SV40 tumors, nuclear fluorescence was detected in each of five cell lines, derived from four mammalian species, transformed by SV40 virus. Essentially all nuclei, including those of multinuclear cells, were fluorescent-stainable. Serum of hamsters bearing SV40 tumors was also found to give nuclear fluorescence in susceptible cells (AGMK or BSC-1) acutely infected with SV40 virus. These findings provide further evidence that cellular incorporation of the SV40 viral genome, with partial expression of the genome by synthesis of at least one virus-specific antigen, is an integral property of all SV40 transformed cells.


[Sarcoidosis in and around the nose: a diagnostic and therapeutic guideline].
In addition to its mucosal pathology, sarcoidosis of the nose may cause a range of skin abnormalities and destruction of the osteocartilaginous structures of the nose. Clinical presentation can mimic other diseases and a biopsy is often necessary. We propose a classification of nasal sarcoidosis based on disease location to help with recognition of the symptoms and, subsequently, treatment. Here we describe 4 patients with nasal sarcoidosis. In the first patient, a 53-year-old woman with a granuloma in the nasal vestibule, the lesion was excised. The second patient, a 38-year-old man with intranasal crusts, synechiae and atrophic mucosa, was treated with corticosteroid nasal drops. The third and fourth patients, a 36-year-old man with progressive widening of the nasal dorsum and a 60-year-old woman with a saddle nose, respectively, were treated with a rhinoplasty.


Extranodal natural killer cell/t-cell lymphoma, nasal type, presenting as cutaneous nodules and a small-bowel perforation.
Extranodal natural killer (NK) cell/T-cell lymphoma, nasal type, is a rare aggressive neoplasm, most commonly presenting as a destructive lesion in the nasal cavity and nasopharynx in middle-aged to older adults. About one third of cases present in an extranasal location, commonly involving skin and gastrointestinal tract, and usually occur in the absence of superficial lymphadenopathy. Diagnosis of this malignancy can be missed given its rarity and heterogeneous presentation. We describe a patient with an extranodal NK cell/T-cell lymphoma, nasal type, who was initially diagnosed and treated for a presumed Mycobacterium marinum infection, after biopsies were unrevealing. However, after more serious complications developed, repeat biopsy was performed. An atypical lymphocytic infiltrate was noted, with cells being positive for NK cell/T-cell markers CD2, CD7, and CD3 (subset), as well as for cytotoxic lymphocyte markers perforin, T-cell intracellular antigen, and CD56. In situ hybridization for Epstein-Barr virus-encoded RNA was also positive. This case demonstrates an important diagnostic pitfall of confusing cutaneous involvement by an aggressive NK cell/T-cell lymphoma with an antibiotic-resistant infection. Repeat biopsies and close clinicopathologic correlation are essential for establishment of correct diagnosis.


[Part-time residency training in Israel].
Full-time work has long been perceived as a cornerstone of medical residency, the consensus being that a resident must apply the bulk of his time and attention to his professional training. Demographic and cultural changes that have taken place over the last several years, specifically the rise in the number of female doctors and the importance of leisure time to the younger generation, have intensified the need to find new and innovative ways to deal with the plight of the resident population. One idea, already in effect in many Western countries, is the institution of part-time residency programs. The possibility of fulfilling residency requirements on a part-time basis is intended to assist medical residents in integrating their professional development with their personal and family life, without compromising the quality of their training. A number of research studies conducted over the last several years in countries that allow part-time residency, among them the United States, England and Switzerland, aimed to examine the quality of part-time training. The various studies evinced a high level of satisfaction from the program both by the residents themselves and their supervisors, and in many aspects those doing residency part-time received higher appraisals than their full-time colleagues. Some of the residents polled noted that they would have totally foregone the practice of medicine had there not been an option to complete residency part-time. In light of the experience throughout the world and the changing landscape in Israel, the Scientific Council of the Israeli Medical Association decided to examine the issue and its various aspects, and weighed all the considerations in favor and against part-time residency. Recently, the Scientific Council approved the launch of a pilot program to allow part-time residency in several fields that were carefully selected according to specific criteria. Once the Ministry of Health completes the LegisLation process, part-time residency will officially begin in Israel.


Doubly negative metamaterials in the near infrared and visible regimes based on thin film nanocomposites.
An optical metamaterial characterized simultaneously by negative permittivity and permeability, viz. doubly negative metamaterial (DNM), that comprises deeply subwavelength unit cells is introduced. The DNM can operate in the near infrared and visible spectra and can be manufactured using standard nanofabrication methods with compatible materials. The DNM's unit cell comprise a continuous optically thin metal film sandwiched between two identical optically thin metal strips separated by a small distance form the film. The incorporation of the middle thin metal film avoids limitations of metamaterials comprised of arrays of paired wires/strips/patches to operate for large wavelength / unit cell ratios. A cavity model, which is a modification of the conventional patch antenna cavity model, is developed to elucidate the structure's electromagnetic properties. A novel procedure for extracting the effective permittivity and permeability is developed for an arbitrary incident angle and those parameters were shown to be nearly angle-independent. Extensions of the presented two dimensional structure to three dimensions by using square patches are straightforward and will enable more isotropic DNMs.


Optimization of 6-heterocyclic-2-(1H-pyrazol-1-yl)-N-(pyridin-2-yl)pyrimidin-4-amine as potent adenosine A2A receptor antagonists for the treatment of Parkinson's disease.
Parkinson's disease is a neurodegenerative disease characterized by the motor symptoms of bradykinesia, tremor, and rigidity. Current therapies are based mainly on dopaminergic replacement strategies by administration of either dopamine agonists or dopamine precursor levodopa (L-Dopa). These treatments provide symptomatic relief without slowing or stopping the disease progression, and long-term usage of these drugs is associated with diminished efficacy, motor fluctuation, and dyskinisia. Unfortunately, there had been few novel treatments developed in the past decades. Among nondopaminergic strategies for the treatment of Parkinson's disease, antagonism of the adenosine A2A receptor has emerged to show great potential. Here we report the optimization of a new chemical scaffold, which achieved exceptional receptor binding affinity and ligand efficiency against adenosine A2A receptor. The leading compounds demonstrated excellent efficacy in the haloperidol induced catalepsy model for Parkinson's disease.


[Membrane differentiation of acute lymphoblastic leukemia from cALL-type cells in diffusion chambers].
In order to explore their differentiation capacity peripheral blasts from 4 children with acute lymphoblastic leukemia of the common type (cALL) as well as cells of the Reh line were cultured in diffusion chambers implanted intraperitoneally into preirradiated CBA mice (8 gy). At various times after initiation of the culture, changes in the membrane marker profile were studied by investigation of surface antigens and rosetting phenomena. In the course of the culture, the cells of two patients, T. H. and I.G., developed surface immunoglobulin (sIg) in combination with the CALL antigen (cALLA). Simultaneously, the cells of I.G. containing cytoplasmic Ig prior to cultivation acquired a receptor for mouse erythrocytes (EM). Besides quite a few cells developing the T-cell antigen, the majority of the cell yield in patient V.M. expressed sIg alone or together with the cALLA. Comparable results together with an increasing portion of mouse rosette forming cells were obtained in the fourth patient, C.M. In case of the Reh-line the cells developed the T-cell antigen, and in one of two experiments they further acquired a receptor for sheep erythrocytes. conversely, in a second experiment and EM-receptor was detected. Our data suggest that leukemic blast cells carrying the cALLA are representative of an early developmental stage of lymphatic ontogeny.


Cell dynamics underlying oriented growth of the Drosophila wing imaginal disc.
Quantitative analysis of the dynamic cellular mechanisms shaping the Drosophila wing during its larval growth phase has been limited, impeding our ability to understand how morphogen patterns regulate tissue shape. Such analysis requires explants to be imaged under conditions that maintain both growth and patterning, as well as methods to quantify how much cellular behaviors change tissue shape. Here, we demonstrate a key requirement for the steroid hormone 20-hydroxyecdysone (20E) in the maintenance of numerous patterning systems in vivo and in explant culture. We find that low concentrations of 20E support prolonged proliferation in explanted wing discs in the absence of insulin, incidentally providing novel insight into the hormonal regulation of imaginal growth. We use 20E-containing media to observe growth directly and to apply recently developed methods for quantitatively decomposing tissue shape changes into cellular contributions. We discover that whereas cell divisions drive tissue expansion along one axis, their contribution to expansion along the orthogonal axis is cancelled by cell rearrangements and cell shape changes. This finding raises the possibility that anisotropic mechanical constraints contribute to growth orientation in the wing disc.


Interleukin-1beta and tumor necrosis factor-alpha upregulate interleukin-23 subunit p19 gene expression in human colonic subepithelial myofibroblasts.
The recently identified cytokine interleukin-23 (IL-23) consists of p19 and p40 subunits. The major cellular source of IL-23 is dendritic cells and/or macrophages. We investigated the expression of IL-23 p19 mRNA in human colonic subepithelial myofibroblasts (SEMFs). p19 mRNA was not expressed in unstimulated SEMFs, but IL-1beta and TNF-alpha strongly induced p19 mRNA expression in these cells. The effects of IL-1beta were much stronger than those of TNF-alpha. These responses were observed in both a dose- and time-dependent manner. Furthermore, these cytokines acted synergistically when used in combination. A blockade of NF-kappaB activation by the overexpression of a stable form of IkappaBalpha completely blocked these responses, indicating that the induction of p19 mRNA expression by IL-1beta and TNF-alpha was mediated by the NF-kappaB activation pathway. In conclusion, this is the first report demonstrating that IL-23 p19 mRNA is inducible in colonic myofibroblasts by IL-1beta and TNF-alpha. The p19 expression in these cells might play a role in mucosal immune responses.


Dopamine transporter DAT and receptor DRD2 variants affect risk of lethal cocaine abuse: a gene-gene-environment interaction.
Epistatic gene-gene interactions could contribute to the heritability of complex multigenic disorders, but few examples have been reported. Here, we focus on the role of aberrant dopaminergic signaling, involving the dopamine transporter DAT, a cocaine target, and the dopamine D2 receptor, which physically interacts with DAT. Splicing polymorphism rs2283265 of DRD2, encoding D2 receptors, were shown to confer risk of cocaine overdose/death (odds ratio ∼3) in subjects and controls from the Miami Dade County Brain Bank.(1) Risk of cocaine-related death attributable to the minor allele of rs2283265 was significantly enhanced to OR=7.5 (P=0.0008) in homozygous carriers of the main 6-repeat allele of DAT rs3836790, a regulatory VNTR in intron8 lacking significant effect itself. In contrast, carriers of the minor 5-repeat DAT allele showed no significant risk (OR=1.1, P=0.84). DAT rs3836790 and DRD2 rs2283265 also interacted by modulating DAT protein activity in the ventral putamen of cocaine abusers. In high-linkage disequilibrium with the VNTR, DAT rs6347 in exon9 yielded similar results. Assessing the impact of DAT alone, a rare DAT haplotype formed by the minor alleles of rs3836790 and rs27072, a regulatory DAT variant in the 3'-UTR, occurred in nearly one-third of the cocaine abusers but was absent in African American controls, apparently conferring strong risk. These results demonstrate gene-gene-drug interaction affecting risk of fatal cocaine intoxication.


Activated coagulation time in monitoring heparinized dogs.
Heparin was administered to normal dogs either IV or subcutaneously and the anticoagulant effects were monitored by determining prolongation of activated partial thromboplastin time (APTT) and activated coagulation time (ACT). Significant correlation was found between ACT and log APTT for all heparin doses. Intravenously administered heparin was rapidly cleared, with the anticoagulant effects lasting only 2 to 3 hours. One hour after IV heparin at dose levels of 100 and 200 U/kg was given, the APTT were prolonged to 1.8 and 2.8 X base-line values, respectively, whereas the ACT were prolonged to 1.4 and 1.6 X base-line values, respectively. Subcutaneously administered heparin was rapidly absorbed, approaching maximal anticoagulation by 2 hours. Thereafter, a fairly stable plateau of anticoagulation was maintained for 4 to 14 hours depending on dose. Two hours after administration of heparin dosages of 250, 500, 750, and 1,000 U/kg, the dog's APTT values were prolonged by 1.6, 2.4, 3.1, and 3.2 X base line, respectively. Corresponding values for ACT revealed prolongations of 1.3, 1.4, 1.6, and 1.7 X base line. Considerable variation in APTT response to a given dose of heparin was noted, particularly in dogs given the higher heparin doses. Subcutaneous heparin administration at a dosage of 500 U/kg maintained an APTT target value of 1.5 to 2.5 X base line for 8 hours. On the basis of the regression line equation, ACT = -7.2 + 73.5 log APTT, ACT values corresponding to the APTT target value ranged from 92.2 to 108.5 s (1.23- to 1.45-fold base line). Monitoring anticoagulation in dogs given subcutaneous heparin is recommended at 2 hours to evaluate maximal anticoagulation effects. The inexpensiveness, technical simplicity, and linear response to heparin support the use of ACT in monitoring heparinized dogs.


Computer low vision aids.
Computers are invading all facets of optometric practice including low vision care. This brief paper will discuss indications for prescribing computer low vision aids, hardware and software currently available, and provide several short case reports to illustrate how the visually impaired individual can utilize this new technology.


Dose-related fluorodeoxyglucose uptake in acute radiation-induced hepatitis.
Therapeutic assessment with fluorine-18 fluorodeoxyglucose (FDG) positron emission tomography (PET) is sometimes problematic after radiation therapy. Herein we describe a patient with acute radiation-induced hepatitis in which PET showed dose-dependent FDG uptake. A 50-year-old man underwent FDG PET for staging of esophageal cancer. Chemoradiotherapy was delivered concurrently with a radiation field that expanded from the esophagus into the upper stomach to cover metastasis of the gastric wall. The patient also underwent FDG PET 26 days and 4 months after chemoradiotherapy to evaluate the therapeutic effect. Twenty-eight days after chemoradiotherapy, hematochemistry revealed elevated hepatic enzymes and postcontrast computed tomography showed band-like hypoattenuation in the liver with parenchymal swelling corresponding to the radiation field. FDG PET performed 26 days after chemoradiotherapy showed a wedge-shaped hypermetabolic area in which the degree of FDG uptake correlated with the prescribed radiation dose. Follow-up PET 4 months after therapy showed no abnormal uptake in the liver. Acute radiation-induced hepatitis can be a potential cause of false-positive findings of malignancy on FDG PET scans, and PET images should carefully be compared with the distribution of prescribed dose. Threshold dose might be higher for metabolic changes than for morphologic changes.


Nonmedical methods to relieve low back pain caused by lumbar disc herniation: a descriptive study in northeastern Turkey.
Low back pain due to the effects of lumbar disc herniation is a common complaint of patients who often subsequently seek help from medical professionals. It is also a significant health problem which is quite difficult to treat. This descriptive study was conducted to determine nonmedical methods used by patients with lumbar disc herniation to relieve low back pain; the patients' intensity of low back pain when they were admitted to the hospital was also explored. Ninety-two patients with lumbar disc herniation participated in this study, which was carried out at a university hospital in northeastern Turkey. Data were collected using a patient information form and the visual analog scale (VAS). When the patients were admitted to hospital, their mean VAS score was 6.56 ± 2.45. The study results showed that as a first choice nearly all of the patients (94.6%) with lumbar disc herniation preferred consulting with their physicians before to obtain relief for low back pain. However, in addition to seeing their physician, more than one-half of these patients (57.6%) also used nonmedical methods. The primary nonmedical methods were hot/cold compresses, wrapping various substances on the back, and herbal preparations. An increase in pain was noted by 17.0% of patients after using nonmedical methods. Findings indicated that more than two-thirds of patients experienced either no change or an increase in pain after using nonmedical methods to find relief.


A Unique Case of Intravascular Lymphoma Mimicking Encephalomyeloradiculoneuropathy.
Angiotropic lymphoma is a rare large B-cell lymphoma involving the intravascular compartment without local tissue or vessel wall infiltration. A 48-year-old male presented with 8 months of progressive paraparesis and bowel and bladder incontinence. Initial cerebrospinal fluid analysis showed high protein, lymphocytic pleocytosis, high IgG synthesis, but no oligoclonal bands. Brain imaging at presentation was unrevealing. Electromyography revealed evidence of bilateral lumbosacral radiculoplexopathy [R>L]. A trial of intravenous solumedrol resulted in significant improvement in weakness. He had multiple hospital admissions for worsening lower extremity weakness, altered mental status, and new-onset upper extremity weakness. Magnetic resonance imaging of the spine revealed abnormal hyperintense T2 signal at T7-T8 level. Visual-evoked potentials revealed significant slowing of conduction in both optic nerves. Repeat electromyography showed a moderate to severe motor axonal polyneuropathy with secondary demyelination in the upper and lower extremities. A working diagnosis of encephalomyeloradiculoneuritis was made because of signs of polyradiculopathy, peripheral neuropathy and myelopathy. Patient had 3 trials of intravenous solumedrol with transient improvement in symptoms. The magnetic resonance imaging brain on his sixth hospital admission revealed multiple areas of restricted diffusion throughout the brain parenchyma. The patient underwent a right frontal lobe biopsy, which showed large CD-20 neoplastic lymphocytes within small arteries, veins, and capillaries with no extension to surrounding brain parenchyma. The findings were consistent with intravascular large B-cell lymphoma. Angiotropic lymphoma is a rare disease with frequent involvement of central nervous system and skin that can present with neurological involvement of both the peripheral and central nervous system.


The good, bad, and the ugly of regenerative therapies for erectile dysfunction.
Erectile dysfunction (ED) is a common condition which reduces quality of life of both patients and their partners, and is a significant health care expense every year. Although phosphodiesterase type-5 inhibitors are the current first-line treatment for men with ED, they are limited by their on-demand dosing, intolerance, and variable efficacy in complex patient populations such as men with multiple medical comorbidities or ED after pelvic surgery. Regenerative medicine has been introduced and investigated in andrology as an encouraging strategy to restore diseased erectile tissue structure and function. Novel regenerative therapies for ED are controversial but are perceived to offer a durable and safe tissue restorative approach to act as a long-term solution to this cumbersome disease process. Here, we review platelet-rich plasma, amniotic fluid membranes, low-intensity extracorporeal shockwave therapy, and stem cell therapy as regenerative strategies to treat ED. Most of these approaches have preclinical and occasionally clinical data to support their ongoing investigation; however, none of these treatments are currently supported for use in ED patients outside of clinical trials.


Simultaneous multi-depth assessment of tissue oxygen saturation in thenar and forearm using near-infrared spectroscopy during a simple cardiovascular challenge.
Hypovolemia and hypovolemic shock are life-threatening conditions that occur in numerous clinical scenarios. Near-infrared spectroscopy (NIRS) has been widely explored, successfully and unsuccessfully, in an attempt to use it as an early detector of hypovolemia by measuring tissue oxygen saturation (StO2). In order to investigate the measurement site dependence and probe dependence of NIRS in response to hemodynamic changes, such as hypovolemia, we applied a simple cardiovascular challenge: a posture change from supine to upright, causing a decrease in stroke volume (as in hypovolemia) and a heart rate increase in combination with peripheral vasoconstriction to maintain adequate blood pressure. Multi-depth NIRS was used in nine healthy volunteers to assess changes in StO2 in the thenar and forearm in response to the hemodynamic changes associated with a posture change from supine to upright. A posture change from supine to upright resulted in a significant increase (P < 0.001) in heart rate. Thenar StO2 did not respond to the hemodynamic changes following the posture change, whereas forearm StO2 did. Forearm StO2 was significantly lower (P < 0.001) in the upright position compared to supine for all probing depths. The primary findings in this study were that forearm StO2 is a more sensitive parameter to hemodynamic changes than thenar StO2 and that the depth at which StO2 is measured is of minor influence. Our data support the use of forearm StO2 as a sensitive parameter for the detection of central hypovolemia and hypovolemic shock in (trauma) patients.


Assessing the trophic ecology and migration on the exposure of cape petrels and Wilson's storm petrels from Antarctica to perfluoroalkylated substances, trace and major elements.
Chemical pollution is a global concern as contaminants are transported and reach even the remote regions of Antarctica. Seabirds serve as important sentinels of pollution due to their high trophic position and wide distribution. This study examines the influence of migration and trophic ecology on the exposure of two Antarctic seabirds, Wilson's storm petrel (Oceanites oceanicus - Ooc), and Cape petrel (Daption capense - Dca), to chemical elements and perfluoroalkyl substances (PFAS). Our methodology involved assessing the concentration of these pollutants in feather samples obtained from carcasses, offering a practical means for monitoring contamination. Trace and major element concentrations were comparable in both species, suggesting that migratory patterns have a minimal impact on exposure levels. However, Ooc had higher concentration of PFAS compared to Dca (mean, ng g-1dry weight, PFOA: Ooc:0.710, Dca:0.170; PFTrDA: Ooc:0.550, Dca:0.360, and PFTeDA: Ooc:1.01, Dca:0.190), indicating that migration to the more polluted Northern Hemisphere significantly affects PFAS exposure. Furthermore, while no strong associations were found between either trace elements or PFAS and the three stable isotopes (δ13C, δ15N, and δ34S), a negative association was observed between PFUnDA and δ15N, hinting at potential biodilution. The research concludes that the migratory patterns of these seabird species affect their PFAS exposure, underscoring the critical need for further exploration and understanding of these relationships to better inform conservation strategies.


Optimized Screening of Coronary Artery Disease With Invasive Coronary Angiography and Ad Hoc Percutaneous Coronary Intervention During Transcatheter Aortic Valve Replacement.
We sought to describe an optimized approach to coronary artery disease (CAD) screening and management in patients undergoing transcatheter aortic valve replacement (TAVR). When invasive coronary angiography showed CAD, the treatment strategy and completeness of revascularization was determined based on coronary anatomy. TAVR was performed in the same setting if percutaneous coronary intervention (PCI) was uncomplicated; otherwise TAVR was postponed. A total of 604 patients undergoing CAD screening at the time of TAVR procedure were prospectively included in this study. Severe CAD was found in 136 patients (22.5%). Among patients with severe CAD, 53 patients (8.8%) underwent uncomplicated PCI. After PCI, TAVR was postponed in 2 patients (0.3%). In 83 patients (13.8%), coronary angiography showed severe CAD that was left untreated. After TAVR, all-cause and cardiovascular 30-day mortality rates were 2.4% and 1.4%, respectively. Disabling stroke, myocardial infarction, and life-threatening bleeding occurred in 0.5%, 0.8%, and 4.0% of patients, respectively. Acute kidney injury II or III rate was 3.3%. At 2 years, all-cause mortality rate was 14.1%. Disabling stroke and myocardial infarction occurred in 2.5% and 1.8% of patients, respectively. Patients undergoing TAVR and PCI in the same session had similar rate of the composite of death, disabling stroke, and myocardial infarction when compared with patients without CAD, and patients with severe CAD left untreated (TAVR+PCI: 10.4%; severe CAD left untreated: 15.4%; no-CAD: 14.8%; P=0.765). In patients undergoing TAVR, screening of CAD with invasive coronary angiography and ad hoc PCI during TAVR is feasible and was not associated with increased periprocedural risks. PCI followed by TAVR in the same session had similar outcomes than TAVR in which PCI was not performed.


Antiasthmatic effects of mediator blockade versus topical corticosteroids in allergic rhinitis and asthma.
To compare the antiasthmatic efficacy of inflammatory mediator blockade versus topical corticosteroid therapy in patients with seasonal allergic rhinitis (SAR) and asthma, 14 patients were enrolled into a single-blind, double-dummy, placebo-controlled crossover study comparing 2 wk therapy of (1) 400 microgram orally inhaled budesonide plus 200 microgram intranasal budesonide (BUD) or (2) 10 mg oral montelukast plus 10 mg oral cetirizine (ML + CZ). Before each treatment period, patients received 7 to 10 d placebo washout. All treatments were given once daily in the morning. Throughout the study, patients recorded the following domiciliary measures: peak expiratory flow (PEF), rescue inhaler requirement, asthma symptoms, and daily activity score. Laboratory measurements were made at trough of adenosine monophosphate (AMP) bronchial challenge and exhaled nitric oxide (NO). Compared with pooled placebo (PL), there were significant (p < 0.05) improvements in all domiciliary measures with both treatments (mean PEF [L/min] PL: 463; BUD: 478; ML + CZ: 483). For geometric mean AMP PC(20) (mg/ml), there was an improvement (p < 0.05), compared with PL (47), for ML + CZ (133) but not for BUD (51); whereas for NO (ppb) there was significant suppression with BUD (7.6) but not ML + CZ (11.5) compared with PL (13.6). In conclusion, both combined mediator blockade and combined topical corticosteroids are equally effective antiasthma therapy in patients with asthma and SAR.


The occurrence and correlates of emotional interdependence in romantic relationships.
Interdependence, including emotional interdependence, is widely considered to be a cornerstone of close relationships. Through frequent interactions, romantic partners are thought to continuously exchange, influence, and respond to one another's emotions, leading their feelings to become closely aligned over time. Although prior research has shown that such emotional interdependence can arise in couples, no research to date has comprehensively investigated its occurrence, degree, consistency and correlates. Across 3 different studies, we examined whether and to what extent couples indeed show interpersonal emotional connections (compared to pseudocouples). Additionally, we investigated its consistency and moderating factors, by examining emotional interdependence across different types of emotions (negative vs. positive vs. emotional extremity), timescales (second-to-second vs. daily life), and situational contexts (supportive vs. conflictual), and by inspecting associations with indicators of relationship closeness (relationship longevity, cohabitation status, commitment, and closeness in terms of including the other in the self). The findings show limited evidence for emotional interdependence. The overall mean level of interdependence was significantly larger than that of randomly composed couples, but only a minority of the couples demonstrated emotional interdependence to a greater extent than these pseudocouples. Moreover, the degree to which couples exhibited emotional interdependence showed little consistency across timescales and contexts, and was not clearly associated with relationship closeness. We discuss potential implications for the field of interpersonal emotion dynamics. (PsycInfo Database Record (c) 2020 APA, all rights reserved).


Community norms for the Eating Disorder Examination Questionnaire (EDE-Q) among gender-expansive populations.
Gender-expansive individuals (i.e., those who identify outside of the binary system of man or woman) are a marginalized group that faces discrimination and have a high burden of mental health problems, but there is a paucity of research on eating disorders in this population. This study aimed to describe the community norms for the Eating Disorder Examination Questionnaire (EDE-Q) in gender-expansive populations. The participants were 988 gender-expansive individuals (defined as neither exclusively cisgender nor binary transgender) from The PRIDE study, an existing longitudinal cohort study of health outcomes in sexual and gender minority people. We present the mean scores, standard deviations, and percentile ranks for the Global score and four subscale scores of the EDE-Q in this group as a whole and stratified by sex assigned at birth. Gender-expansive individuals reported any occurrence (≥1/28 days) of dietary restraint (23.0%), objective binge episodes (12.9%), excessive exercise (7.4%), self-induced vomiting (1.4%), or laxative misuse (1.2%). We found no statistically significant differences by sex assigned at birth. Compared to a prior study of transgender men and women, there were no significant differences in eating attitudes or disordered eating behaviors noted between gender-expansive individuals and transgender men. Transgender women reported higher Restraint and Shape Concern subscale scores compared to gender-expansive individuals. Compared to a prior study of presumed cisgender men 18-26 years, our age-matched gender-expansive sample had higher Eating, Weight, and Shape Concern subscales and Global Score, but reported a lower frequency of objective binge episodes and excessive exercise. Compared to a prior study of presumed cisgender women 18-25 years, our age-matched gender-expansive sample had a higher Shape Concern subscale score, a lower Restraint subscale score, and lower frequencies of self-induced vomiting, laxative misuse, and excessive exercise. Gender-expansive individuals reported lower Restraint and Shape Concern scores than transgender women; higher Eating, Weight, and Shape Concern scores than presumed cisgender men; and lower Restraint but higher Shape Concern scores than presumed cisgender women. These norms can help clinicians in treating this population and interpreting the EDE-Q scores of their gender-expansive patients.