I-131 anti-B1 therapy/tracer uptake ratio using a new procedure for fusion of tracer images to computed tomography images.
In patients with non-Hodgkin's lymphoma being treated by I-131-radiolabeled anti-B1 monoclonal antibody, we test the hypothesis that the activity taken up in tumors during therapy is the same as that observed during tracer evaluation, except for scaling by the ratio of administered activities. Chemotherapy-relapsed patients are imaged only with planar conjugate views, whereas previously untreated patients are imaged with planar conjugate views and with single-photon emission computed tomography (SPECT). The SPECT tracer activity quantification requires computed tomography (CT) to SPECT image fusion, for which we devised a new procedure: first, the tracer SPECT images are fused to the therapy SPECT images. Then, that transformation is combined with the therapy SPECT-to-CT transformation. We also use (a) the same volumes of interest defined on CT for both tracer and therapy image sets, and (b) a SPECT counts-to-activity conversion factor that adapts to background and rotation radius. We define R as the ratio of therapy activity percentage of infused dose over tracer activity percentage of infused dose at 2-3 days after monoclonal antibody infusion. For 31 chemotherapy-relapsed patients, the R ratio for 60 solitary or composite tumors averages 0.931 +/- 0.031. The hypothesis of R being 1 is rejected with greater than 95% confidence. However, the difference from 1 is only 7.4%. The range of R is 0.43-1.55. For seven previously untreated patients, R averages 1.050 +/- 0.050 for 24 solitary tumors evaluated by SPECT. For six of these patients, R averages 0.946 +/- 0.098 for one of these solitary tumors and for five composite tumors, evaluated by conjugate views. Both results agree with the hypothesis that R is 1. The range of R for the SPECT tumors is 0.71 +/- 0.03 to 1.82 +/- 0.53, and for the conjugate view tumors, it is 0.70-1.35. Plots of R versus tumor volume yield small correlation coefficients. That from SPECT approaches a statistically significant difference from zero correlation (P = 0.06). In summary, on average, the tumor percentage of infused dose following tracer administration is predictive of therapeutic percentage of infused dose within 8%. For greater accuracy with individual tumors, however, an intratherapy evaluation is probably necessary because the range of R is large.


Highly Emissive 9-Borafluorene Derivatives: Synthesis, Photophysical Properties and Device Fabrication.
A series of 9-borafluorene derivatives, functionalised with electron-donating groups, have been prepared. Some of these 9-borafluorene compounds exhibit strong yellowish emission in solution and in the solid state with relatively high quantum yields (up to 73.6 % for FMesB-Cz as a neat film). The results suggest that the highly twisted donor groups suppress charge transfer, but the intrinsic photophysical properties of the 9-borafluorene systems remain. The new compounds showed enhanced stability towards the atmosphere, and exhibited excellent thermal stability, revealing their potential for application in materials science. Organic light-emitting diode (OLED) devices were fabricated with two of the highly emissive compounds, and they exhibited strong yellow-greenish electroluminescence, with a maximum luminance intensity of >22 000 cd m-2 . These are the first two examples of 9-borafluorene derivatives being used as light-emitting materials in OLED devices, and they have enabled us to achieve a balance between maintaining their intrinsic properties while improving their stability.


The Healthy Eating Index-2010 is a valid and reliable measure of diet quality according to the 2010 Dietary Guidelines for Americans.
The Healthy Eating Index (HEI), a measure of diet quality, was updated to reflect the 2010 Dietary Guidelines for Americans and the accompanying USDA Food Patterns. To assess the validity and reliability of the HEI-2010, exemplary menus were scored and 2 24-h dietary recalls from individuals aged ≥2 y from the 2003-2004 NHANES were used to estimate multivariate usual intake distributions and assess whether the HEI-2010 1) has a distribution wide enough to detect meaningful differences in diet quality among individuals, 2) distinguishes between groups with known differences in diet quality by using t tests, 3) measures diet quality independently of energy intake by using Pearson correlation coefficients, 4) has >1 underlying dimension by using principal components analysis (PCA), and 5) is internally consistent by calculating Cronbach's coefficient α. HEI-2010 scores were at or near the maximum levels for the exemplary menus. The distribution of scores among the population was wide (5th percentile = 31.7; 95th percentile = 70.4). As predicted, men's diet quality (mean HEI-2010 total score = 49.8) was poorer than women's (52.7), younger adults' diet quality (45.4) was poorer than older adults' (56.1), and smokers' diet quality (45.7) was poorer than nonsmokers' (53.3) (P < 0.01). Low correlations with energy were observed for HEI-2010 total and component scores (|r| ≤ 0.21). Cronbach's coefficient α was 0.68, supporting the reliability of the HEI-2010 total score as an indicator of overall diet quality. Nonetheless, PCA indicated multiple underlying dimensions, highlighting the fact that the component scores are equally as important as the total. A comparable reevaluation of the HEI-2005 yielded similar results. This study supports the validity and the reliability of both versions of the HEI.


Altered lung metabolism and mitochondrial DAMPs in lung injury due to acute kidney injury.
Acute respiratory distress syndrome (ARDS) is a common cause of mortality in patients with acute kidney injury (AKI). Inflammatory crosstalk from the kidney to the lung has been shown to contribute to lung injury after AKI, but anti-inflammatory therapies have not been proven beneficial in human studies. Recently, AKI was shown to alter mitochondria and related metabolic pathways in the heart, but the impact of AKI on lung metabolism has not been investigated to our knowledge. In this study, we evaluated the metabolomic profile of the lung following renal ischemia and reperfusion to identify novel pathways that may be modifiable. We randomized C57BL/6 mice to 20 minutes of bilateral renal arterial clamping or sham operation under ketamine/xylazine anesthesia. At 4 hours after reperfusion, we found a significant increase in markers of lung injury, as well as significant metabolomic changes across lung, kidney, plasma and bronchoalveolar lavage fluid (BALF) compared to shams. Comparative analyses revealed that the fatty acid oxidation pathway was the most significantly altered metabolic pathway, a finding which is consistent with mitochondrial dysfunction systemically and in the lung. These metabolomic changes correlated with the extracellular accumulation of the mitochondrial damage associated molecular patterns (mtDAMPs), mitochondrial DNA (mtDNA) and transcription factor A, mitochondria (TFAM). Finally, we found that intraperitoneal injection of renal mtDAMPs caused metabolomic changes consistent with mitochondrial dysfunction in the lung in vivo. Mitochondrial function and mtDAMPs warrant further investigation as potential therapeutic targets in preventing lung injury because of AKI.


The threat of honey bee RNA viruses to yellow-legged hornets: Insights from cross-species transmission events.
Viral diseases are a significant challenge in beekeeping, and recent studies have unveiled a potential link between these diseases and the yellow-legged hornets (Vespa velutina), notorious predators of honey bees. However, it remains unclear whether virus diseases are commonly shared between honey bees and hornets or are merely sporadic cross-species transmission events. To address this knowledge gap, we conducted a study utilizing hornet-keeping practices in Yunnan, Southwest China. Our findings demonstrate that deformed wing virus (DWV-A) and Israeli acute paralysis virus (IAPV) can be transmitted from honey bees to yellow-legged hornets. We detected virus replication in various hornet stages, including pupae with IAPV infections, indicating the similarities between infected hornet and honey bee stages. Furthermore, we observed signs and infection intensities of DWV-A and IAPV comparable to those in honey bees. While different polymorphisms were found in the virus isolates from yellow-legged hornets, the sequences remain similar to honey bee counterparts. While our findings suggest that DWV-A and IAPV behave like common diseases, we observed a natural elimination of the viruses in hornet colonies, with minimal alterations in viral sequences. Consequently, these events appear to be cross-species transmission from honey bees, with yellow-legged hornets acting as potential incidental hosts. Further investigations of virus monitoring in hornets promise valuable insights into the disease ecology of bee-infecting viruses.


Nocturnal enuresis and daytime wetting: a multicentric trial with oxybutynin and desmopressin.
Different etiopathological mechanisms of enuresis are today under study, and different therapies and drugs have been proposed. The Italian Multicentric Trial was undertaken in twelve pediatric and urological centers in order to assess the efficacy of two of the most popular drugs, desmopressin (DDAVP) and oxybutynin. 114 enuretic patients were enrolled in the study. After a 2-week observation period, 66 patients with primary monosymptomatic enuresis were treated with DDAVP, 30 micrograms/day intranasally, for 6 weeks, 48 patients with enuresis and voiding dysfunction were randomly assigned to a protocol with oxybutynin alone or oxybutynin plus DDAVP. The efficacy of the two drugs was measured in terms of reduction of wet nights per week during the 6-week treatment period and a 2-week follow-up period. Children with 0-3 dry nights/week were considered as nonresponders. Patients with monosymptomatic enuresis treated with DDAVP reported a significantly lower number of wet night during treatment than during the baseline period, with 79% showing a 'good' (6-7 dry nights/week) or 'intermediate' response (4-5 dry nights/week). Of the patients with diurnal voiding disturbances and enuresis, those treated with oxybutynin alone had a 54% success rate. The patients treated with both oxybutynin and DDAVP showed a better response, with a 71% rate of success. The efficacy of the two drugs is confirmed in patients carefully selected on the clinical basis of voiding disturbances. In patients with enuresis and voiding dysfunction, the reduced urinary output and the lower bladder filling rate due to DDAVP can reduce uninhibited bladder contractions, thus enhancing the oxybutynin action.


Smad4 promotes differentiation of effector and circulating memory CD8 T cells but is dispensable for tissue-resident memory CD8 T cells.
Tissue-resident memory CD8 T cells are a unique subset of virus-specific CTLs that bolster local immune responses after becoming lodged in previously infected tissues. These cells provide enhanced protection by intercepting returning pathogens before a new infection gets established. In contrast, central memory CD8 T cells circulate in the bloodstream and proliferate in secondary lymphoid organs before replenishing effector and memory CD8 T cell populations in remote parts of the body. Both populations of virus-specific memory CD8 T cells participate in immunity to influenza virus infection; however, the signaling pathways that instruct developing memory CD8 T cells to distribute to specific tissues are poorly defined. We show that TGF-β promotes the development of pulmonary tissue-resident memory T cells via a signaling pathway that does not require the downstream signaling intermediate Sma- and Mad-related protein (Smad)4. In contrast, circulating memory CD8 T cells have no requirement for TGF-β but show signs of arrested development in the absence of Smad4, including aberrant CD103 expression. These signaling pathways alter the distribution of virus-specific CTLs in the lungs but do not prevent robust cytokine responses. Our data show that Smad4 is required for normal differentiation of multiple subsets of virus-specific CD8 T cells. In normal circumstances, Smad4 may be activated via a pathway that bypasses the TGF-β receptor. Improved understanding of these signaling pathways could be used to augment vaccine-induced immunity.


Subcellular Targeting of VIP Boutons in Mouse Barrel Cortex is Layer-Dependent and not Restricted to Interneurons.
Neocortical vasoactive intestinal polypeptide (VIP) expressing cells are a diverse subpopulation of GABAergic interneurons issuing distinct axonal projections. They are known to inhibit other types of interneurons as well as excitatory principal neurons and possess a disinhibitory net effect in cortical circuits. In order to elucidate their targeting specificity, the output connectivity of VIP interneurons was studied at the subcellular level in barrel cortex of interneuron-specific Cre-driver mice, using pre- and postembedding electron microscopy. Systematically sampling VIP boutons across all layers, we found a substantial proportion of the innervated subcellular structures were dendrites (80%), with somata (13%), and spines (7%) being much less targeted. In layer VI, a high proportion of axosomatic synapses was found (39%). GABA-immunopositive ratio was quantified among the targets using statistically validated thresholds: only 37% of the dendrites, 7% of the spines, and 26% of the somata showed above-threshold immunogold labeling. For the main target structure "dendrite", a higher proportion of GABAergic subcellular profiles existed in deep than in superficial layers. In conclusion, VIP interneurons innervate non-GABAergic excitatory neurons and interneurons at their subcellular domains with layer-dependent specificity. This suggests a diverse output of VIP interneurons, which predicts multiple functionality in cortical circuitry beyond disinhibition.


Professional burnout and work satisfaction in Spanish allergists: analysis of working conditions in the specialty.
Burnout is a worrying problem in the medical profession and has proven to be highly prevalent in all the care settings and specialty areas in which it has been studied.We applied 2 widely used questionnaires to analyze the working conditions of Spanish allergists in terms of quality of professional life and degree of burnout perceived. Participants completed 2 questionnaires: the 22-item Maslach scale, a structured questionnaire covering different aspects of the feelings and attitudes of professionals toward their work and patients; and the Spanish Quality of Professional Life Questionnaire (CPV-35), a 35-item questionnaire evaluating job satisfaction and perceived quality of life at work. We received 404 questionnaires from throughout Spain. The main sources of motivation were better pay (94.4%), more available resources/technology (85.1%), access to research activities (81%), and promotion in one's professional career (80.1%). Analysis of the scores from the Maslach scale revealed that two-thirds of the allergists interviewed experienced medium and high levels of negative burnout (67.9% and 66.2%, respectively, for emotional exhaustion and depersonalization). This situation was in part compensated for by the fact that a slightly lower proportion of the group (59.2%) obtained very high scores on personal accomplishment in their work. Analysis of the scores from the CPV-35 questionnaire revealed 3 complementary aspects of job satisfaction: perceptions of the workload borne (5.8), management support available to cope with daily patient workload (5.6), and levels of intrinsic motivation for work (7.7), which was the highest value. The score for the item summarizing self-perceived overall quality of working life was acceptable (6.4). Promoting intrinsic motivation of Spanish allergists using the motivating factors identified in this study could protect against professional burnout.


Resilience-recovery factors in post-traumatic stress disorder among female and male Vietnam veterans: hardiness, postwar social support, and additional stressful life events.
Structural equation modeling procedures were used to examine relationships among several war zone stressor dimensions, resilience-recovery factors, and post-traumatic stress disorder symptoms in a national sample of 1,632 Vietnam veterans (26% women and 74% men). A 9-factor measurement model was specified on a mixed-gender subsample of the data and then replicated on separate subsamples of female and male veterans. For both genders, the structural models supported strong mediation effects for the intrapersonal resource characteristic of hardiness, postwar structural and functional social support, and additional negative life events in the postwar period. Support for moderator effects or buffering in terms of interactions between war zone stressor level and resilience-recovery factors was minimal.


B-type natriuretic peptide forms within the heart, coronary sinus, and peripheral circulation in humans: evidence for degradation before secretion.
The B-type natriuretic peptides (BNP and N-terminal pro-BNP) are secreted by the heart and, in the case of BNP, serve to maintain circulatory homeostasis through renal and vascular actions and oppose many effects of the renin-angiotensin system. Recent evidence suggests that in patients with severe heart failure, circulating immunoreactive BNP is made up mainly of metabolites that may have reduced bioactivity. We hypothesized that BNP may be degraded before it even leaves the heart. Peripheral venous plasma plus atrial and ventricular tissue, obtained from explanted hearts at the time of transplantation, were collected from 3 patients with end-stage heart failure. In a separate study, plasma was collected from the coronary sinus and femoral artery of 3 separate patients undergoing cardiac catheterization. Plasma C18 reverse-phase extracts were separated on reverse-phase HPLC, and the collected fractions were subjected to RIAs with highly specific antisera directed to the amino- and carboxy-terminal ends of BNP(1-32). ProBNP, BNP(1-32), and 2 major BNP metabolites were present in atrial and ventricular tissue, where BNP(1-32) represented 45% and 70% of total processed BNP, respectively. Neither BNP(1-32) nor the 2 metabolites were detected in peripheral venous plasma. Nor was BNP(1-32) detected in matching coronary sinus and femoral artery plasma from the 3 patients undergoing cardiac catheterization. BNP(1-32) is partly degraded within the hearts of patients with end-stage heart failure, and even in patients with relatively well-preserved left ventricular systolic function, only BNP metabolites enter the systemic circulation.


Clinical significance of in vitro synergism between antibiotics in gram-negative infections.
Five combinations of antibiotics (ampicillin/gentamicin, cephalothin/gentamicin, carbenicillin/gentamicin, polymyxin/carbenicillin, and carbenicillin/cephalothin) were investigated in vitro and in 148 severe infectious episodes caused by gram-negative bacilli in patients with disseminated cancer. The use of combinations that were synergistic in vitro against the offending microorganism (synergy was defined as occurring when the minimal inhibitory concentration of each of the drugs in the combination was one-quarter or less of the minimal inhibitory concentration of each drug alone) was associated with a significantly better response to antibacterial therapy (P < 0.01) than the use of combinations that were not synergistic against the causative agent.


Prognostic factors for critically ill surgical patients with unplanned intensive care unit readmission: Developing a novel predictive scoring model for predicting readmission.
Unplanned readmission to the surgical intensive care unit has been demonstrated to worsen patient outcomes. Our objective was to identify risk factors and outcomes associated with unplanned surgical intensive care unit readmission and to develop a predictive scoring model to identify patients at high risk of readmission. We retrospectively analyzed patients admitted to the surgical intensive care unit (2020-2021) and categorized them as either with or without unplanned readmission. Of 1,112 patients in the derivation cohort, 76 (6.8%) experienced unplanned surgical intensive care unit readmission, with sepsis being the leading cause of readmission (35.5%). Patients who were readmitted had significantly higher in-hospital mortality rates than those who were not. Multivariate analysis identified congestive heart failure, high Sequential Organ Failure Assessment-Hepatic score, use of carbapenem during surgical intensive care unit stay, as well as factors before surgical intensive care unit discharge such as inadequate glycemic control, positive fluid balance, low partial pressure of oxygen in arterial blood/fraction of inspired oxygen ratio, and receipt of total parenteral nutrition as independent predictors for unplanned readmission. The scoring model developed using these predictors exhibited good discrimination between readmitted and non-readmitted patients, with an area under the curve of 0.74. The observed rates of unplanned readmission for scores of <4 points and ≥4 points were 4% and 20.2% (P < .001), respectively. The model also demonstrated good performance in the validation cohort, with an area under the curve of 0.74 and 19% observed unplanned readmission rate for scores ≥4 points. Besides congestive heart failure, clinicians should meticulously re-evaluate critical variables such as the Sequential Organ Failure Assessment-Hepatic score, partial pressure of oxygen in arterial blood/fraction of inspired oxygen ratio, glycemic control, and fluid status before releasing the patient from the surgical intensive care unit. It is crucial to determine the reasons for using carbapenems during surgical intensive care unit stay and the causes for the inability to discontinue total parenteral nutrition before discharging the patient from the surgical intensive care unit.


[The catalytic wet air oxidation reaction of acetic acid with Ti-Ce series catalyst].
The influence factors and reaction mechanism during the catalytic wet air oxidation of acetic acid with Ti-Ce series catalyst was investigated in this paper. The results show that the reaction was influenced by the catalyst load, the reaction temperature, the pH of the reaction system and the partial pressure of oxygen. More than 90% removal efficiency of acetic acid (as COD) can be obtained at the reaction conditions as follow: temperature 230 degrees C, oxygen partial pressure 2-2.5 MPa, catalyst amount 5 g/L, initial pH of the system 3.0 and reaction time 1 h. With Ion Chromatography, the formic acid formed during the reaction process was detected. The formic was found during the wet air oxidation of acetic acid in the absence of catalyst, but can not be detected during the catalytic wet air oxidation process with Ti-Ce catalyst. It means that the presence of catalyst in the system not only improve the removal efficiency, but also change the oxidation pathway.


Prediction of in vivo radiation dose status in radiotherapy patients using ex vivo and in vivo gene expression signatures.
After a large-scale nuclear accident or an attack with an improvised nuclear device, rapid biodosimetry would be needed for triage. As a possible means to address this need, we previously defined a gene expression signature in human peripheral white blood cells irradiated ex vivo that predicts the level of radiation exposure with high accuracy. We now demonstrate this principle in vivo using blood from patients receiving total-body irradiation (TBI). Whole genome microarray analysis has identified genes responding significantly to in vivo radiation exposure in peripheral blood. A 3-nearest neighbor classifier built from the TBI patient data correctly predicted samples as exposed to 0, 1.25 or 3.75 Gy with 94% accuracy (P < 0.001) even when samples from healthy donor controls were included. The same samples were classified with 98% accuracy using a signature previously defined from ex vivo irradiation data. The samples could also be classified as exposed or not exposed with 100% accuracy. The demonstration that ex vivo irradiation is an appropriate model that can provide meaningful prediction of in vivo exposure levels, and that the signatures are robust across diverse disease states and independent sample sets, is an important advance in the application of gene expression for biodosimetry.


Recent progress in psychiatric genetics-some hope but no hype.
The reputation of the field of psychiatric genetics has recently become tarnished in the view of many human geneticists. Too many linked loci were claimed and withdrawn, too many association studies published and not confirmed and, more recently, too many new and different chromosomal regions have been implicated for the same disorder. Here, we summarize recent trends, focusing on research that moves away from traditional linkage studies. Some promising strategies include psychopharmacogenetics, and consideration of endophenotypes such as neurophysiological and behavioral markers in addition to the clinical diagnosis. Utilization of rapid and automated methods for scoring genetic variants in large-scale association studies followed by multivariate analyses, which include environmental as well as genetic data, will likely fare better than traditional linkage analysis in disentangling the complex genetics of psychiatric disorders. Some notable areas of recent progress include quantification of the genetic complexity of autism, identification of genetic variants protecting individuals from alcoholism, and the description of several polymorphisms likely to be relevant to behavior and psychiatry. The most notable example may be a common variant that affects the transcription rate in the promoter for the serotonin transporter gene that may be relevant for individual differences in the response to common anti-depressants.


Extraction of Light Using Random Nanocone on Poly(vinyl-butyral) for Flexible OLEDs.
In this study, we designed a smooth, highly flexible, mechanically robust poly(vinyl-butyral) (PVB)/silver nanowire (AgNW) composite transparent conducting electrode (TCE) integrated with a random nanocone (RNC) to enhance the light extraction of flexible organic light-emitting diodes (OLEDs). The RNC was fabricated by reactive-ion etching (RIE) on AgNW embedded in PVB. As the etching time increased, the size of the RNC became larger. The sheet resistance and transmittance of PVB/AgNW with the RNC was 21.7 Ω/sq and ~87%, respectively. For the PVB/AgNW, the change in sheet resistance was only 2.6% when a 2,000-bend test was performed. The maximum external quantum efficiency was 28.3% when RNC 700 s was used as a green phosphorescent OLED. In addition, for current efficiency and power efficiency, RNC 700 s increased 1.4 times over RNC 0 s. RNC is free of viewing-angle-dependent color and brightness distortion. PVB/AgNW and RNC are practical ways to overcome the brittleness of conventional indium tin oxide and improve the efficiency of flexible OLEDs. Finally, this product is expected to be applied to various flexible optical devices.


Synaptic dysregulation and hyperexcitability induced by intracellular amyloid beta oligomers.
Intracellular amyloid beta oligomer (iAβo) accumulation and neuronal hyperexcitability are two crucial events at early stages of Alzheimer's disease (AD). However, to date, no mechanism linking iAβo with an increase in neuronal excitability has been reported. Here, the effects of human AD brain-derived (h-iAβo) and synthetic (iAβo) peptides on synaptic currents and action potential firing were investigated in hippocampal neurons. Starting from 500 pM, iAβo rapidly increased the frequency of synaptic currents and higher concentrations potentiated the AMPA receptor-mediated current. Both effects were PKC-dependent. Parallel recordings of synaptic currents and nitric oxide (NO)-associated fluorescence showed that the increased frequency, related to pre-synaptic release, was dependent on a NO-mediated retrograde signaling. Moreover, increased synchronization in NO production was also observed in neurons neighboring those dialyzed with iAβo, indicating that iAβo can increase network excitability at a distance. Current-clamp recordings suggested that iAβo increased neuronal excitability via AMPA-driven synaptic activity without altering membrane intrinsic properties. These results strongly indicate that iAβo causes functional spreading of hyperexcitability through a synaptic-driven mechanism and offers an important neuropathological significance to intracellular species in the initial stages of AD, which include brain hyperexcitability and seizures.


Observational study of adherence to a traditional Mediterranean diet, sociocultural characteristics and cardiovascular disease risk factors of older Greek Australians from MEDiterranean ISlands (MEDIS-Australia Study): Protocol and rationale.
To describe the study protocol of the MEDiterranean ISlands-Australia (MEDIS-Australia) Study modelled on the MEDIS Study conducted in Greece. The present study aims to explore adherence to the traditional Mediterranean diet pattern, determine enablers and barriers to adherence, explore the definition of Greek cuisine, and associations between adherence to the diet pattern and risk factors for cardiovascular disease (CVD) and metabolic syndrome in older Greek Australians originally from Greek islands and Cyprus. Now long-term immigrants, with at least 50 years in Australia, characteristics and risk factor profiles of older Greek islander-born Australians will be compared and contrasted to their counterparts living on Greek islands to evaluate the influence of migration on adherence. The present study is an observational study of cross-sectional design using a modified lifestyle and semi-quantitative food frequency questionnaire to capture sociodemographic, health, psychosocial and dietary characteristics, including cuisine, of 150 older Greek islander-born Australians. Anthropometric measures and medical history will be collected. Participants will be aged over 65 years, live independently, are originally from a Greek island and are free from CVD. Data collection is underway. Characteristics and behaviours associated with adherence, if identified, could be evaluated in future studies. For example, exploration of enablers or barriers to adherence to a Mediterranean dietary pattern in an Australian population.


Trade-offs in antibody repertoires to complex antigens.
Pathogens vary in their antigenic complexity. While some pathogens such as measles present a few relatively invariant targets to the immune system, others such as malaria display considerable antigenic diversity. How the immune response copes in the presence of multiple antigens, and whether a trade-off exists between the breadth and efficacy of antibody (Ab)-mediated immune responses, are unsolved problems. We present a theoretical model of affinity maturation of B-cell receptors (BCRs) during a primary infection and examine how variation in the number of accessible antigenic sites alters the Ab repertoire. Naive B cells with randomly generated receptor sequences initiate the germinal centre (GC) reaction. The binding affinity of a BCR to an antigen is quantified via a genotype-phenotype map, based on a random energy landscape, that combines local and distant interactions between residues. In the presence of numerous antigens or epitopes, B-cell clones with different specificities compete for stimulation during rounds of mutation within GCs. We find that the availability of many epitopes reduces the affinity and relative breadth of the Ab repertoire. Despite the stochasticity of somatic hypermutation, patterns of immunodominance are strongly shaped by chance selection of naive B cells with specificities for particular epitopes. Our model provides a mechanistic basis for the diversity of Ab repertoires and the evolutionary advantage of antigenically complex pathogens.


Mucociliary differentiation according to time in human nasal epithelial cell culture.
Knowledge of the state of differentiation, cell phenotype, and expression of genes for mucus production at the time of study is important because these may vary at different times during the culture period. The primary purpose of this study was to determine whether the number of ciliated cells increases as a function of differentiation in NHNE cells. If we observed an increase in the number of ciliated cells, the composition ratio of ciliated and secretory cells according to the culture duration was determined. The levels of mucin and lysozyme secretion and their gene expression at this time were also examined. The presence of ciliated cells was not evident up to 2 days after confluence. However, 3.1 +/- 0.2 %, 7.4 +/- 0.5 %, and 14.5 +/- 0.6 % of the cells were ciliated on the 7th, the 14th, and the 28th day after confluence, respectively. Meanwhile, the percentage of secretory cells were 35.6 +/- 2.8 %, 32.8 +/- 2.5 %, 32.8 +/- 2.5 %, and 49.4 +/- 1.4 % on the 2nd, the 7th, 14th, and 28th day after confluence. The amount of secreted mucin showed an abruptly increasing pattern by the 14th day after confluence but showed no significant changes thereafter. The amount of secreted lysozyme increased as a function of differentiation. MUC5AC and MUC5B mRNA were mainly expressed between the 7th and the 14th day after confluence with relatively weak MUC8 and lysozyme expression. By the 28th day after confluence however, as the MUC5AC mRNA expression became weaker, MUC5B, MUC8, and lysozyme mRNA expression became stronger. In conclusion, we speculate that in in vitro studies with NHNE cells, the time point of treatment should vary according to the purpose of the study. In addition, the MUC5B and MUC8 gene may play an important role in mucin secretion in fully differentiated human nasal epithelial cells.


Right ventricular myocardial biomarkers in human heart failure.
Right ventricular (RV) dysfunction contributes to mortality in chronic heart failure (HF). However, the molecular mechanisms of RV failure remain poorly understood, and RV myocardial biomarkers have yet to be developed. We performed RNA sequencing (RNA-seq) on 22 explanted human HF RVs and 5 unused donor human heart RVs (DON RV) and compared results to those recently reported from 16 explanted human LVs We used Bowtie-Tophat for transcript alignment and transcriptome assembly, DESeq for identification of differentially expressed genes (DEGs) and Ingenuity for exploration of gene ontologies. In the HF RV, RNA-seq identified 130,790 total RNA transcripts including 13,272 protein coding genes, 10,831 long non-coding RNA genes and 8,605 pseudogenes. There were 800-1000 DEGs between DON and HF RV comparison groups with differences concentrated in cytoskeletal, basement membrane, extracellular matrix (ECM), inflammatory mediator, hemostasis, membrane transport and transcription factor genes, lncRNAs and pseudogenes. In an unbiased approach, the top 10 DEGs SERPINA3, SERPINA5, LCN6, LCN10, STEAP4, AKR1C1, STAC2, SPARCL1, VSIG4 and F8 exhibited no overlap in read counts between DON and HF RVs, high sensitivities, specificities, predictive values and areas under the receiver operating characteristic curves. STEAP4, SPARCL1 and VSIG4 were differentially expressed between RVs and LVs, supporting their roles as RV-specific myocardial biomarkers. Unbiased, comprehensive profiling of the RV transcriptome by RNA-seq suggests structural changes and abnormalities in inflammatory processes and yields specific, novel HF RV vs HF LV myocardial biomarkers not previously identified by more limited transcriptome profiling approaches.


Modeling Singlet Fission on a Quantum Computer.
We demonstrate a practical application of quantum computing by using it to investigate the linear H4 molecule as a simple model for singlet fission. We use the Peeters-Devreese-Soldatov energy functional to calculate the necessary energetics based on the moments of the Hamiltonian estimated on the quantum computer. To reduce the number of required measurements, we use several independent strategies: 1) reduction of the size of the relevant Hilbert space by tapering off qubits; 2) measurement optimization via rotations to eigenbases shared by groups of qubit-wise commuting Pauli strings; and 3) parallel execution of multiple state preparation and measurement operations using all 20 qubits available on the Quantinuum H1-1 quantum hardware. Our results meet the energetic requirements for singlet fission, are in excellent agreement with exact transition energies (for the chosen one-particle basis), and outperform classical methods considered computationally feasible for singlet fission candidates.


Preoperative and adjuvant chemotherapy in non-small cell lung cancer.
In non-small cell lung cancer (NSCLC), if the tumor is completely resected in stage I, II, and IIIa disease, the outlook is favorable. In stage IIIa disease, preoperative chemotherapy is efficacious and also confers the potential for improved resectability rates and survival. In a study of 58 patients with locally advanced (stage IIIa) NSCLC, preoperative combination chemotherapy with mitomycin C, cisplatin, and vinca alkaloids yielded 7 complete responses and 37 partial responses. Of the 44 patients with major responses, 42 were surgically explored and 33 were completely resected. Nine patients had pathologically negative biopsy specimens. The median survival for all patients thus far is 19.5 months. These results indicate that surgery can be performed safely in patients treated preoperatively with currently available chemotherapeutic agents. Moreover, complete resections are feasible and can be accomplished in a majority of patients.


Evaluating efficiency and robustness in cilia design.
Motile cilia are used by many eukaryotic cells to transport flow. Cilia-driven flows are important to many physiological functions, yet a deep understanding of the interplay between the mechanical structure of cilia and their physiological functions in healthy and diseased conditions remains elusive. To develop such an understanding, one needs a quantitative framework to assess cilia performance and robustness when subject to perturbations in the cilia apparatus. Here we link cilia design (beating patterns) to function (flow transport) in the context of experimentally and theoretically derived cilia models. We particularly examine the optimality and robustness of cilia design. Optimality refers to efficiency of flow transport, while robustness is defined as low sensitivity to variations in the design parameters. We find that suboptimal designs can be more robust than optimal ones. That is, designing for the most efficient cilium does not guarantee robustness. These findings have significant implications on the understanding of cilia design in artificial and biological systems.


Disrupted yeast mitochondria can import precursor proteins directly through their inner membrane.
Import of precursor proteins into the yeast mitochondrial matrix can occur directly across the inner membrane. First, disruption of the outer membrane restores protein import to mitochondria whose normal import sites have been blocked by an antibody against the outer membrane or by a chimeric, incompletely translocated precursor protein. Second, a potential- and ATP-dependent import of authentic or artificial precursor proteins is observed with purified inner membrane vesicles virtually free of outer membrane components. Third, import into purified inner membrane vesicles is insensitive to antibody against the outer membrane. Thus, while outer membrane components are clearly required in vivo, the inner membrane contains a complete protein translocation system that can operate by itself if the outer membrane barrier is removed.


[Bilateral angle-closure glaucoma induced by topiramate].
Topiramate (TPM) is a drug used in migraine prophylaxis. It is involved in the bilateral angle-closure glaucoma due to idiosyncratic response. This side effect is rare but can lead to irreversible vision loss if it is not recognized in time and if it is not managed immediately by an ophthalmologist.


Bacterial contact induces polar plug disintegration to mediate whipworm egg hatching.
The bacterial microbiota promotes the life cycle of the intestine-dwelling whipworm Trichuris by mediating hatching of parasite eggs ingested by the mammalian host. Despite the enormous disease burden associated with Trichuris colonization, the mechanisms underlying this transkingdom interaction have been obscure. Here, we used a multiscale microscopy approach to define the structural events associated with bacteria-mediated hatching of eggs for the murine model parasite Trichuris muris. Through the combination of scanning electron microscopy (SEM) and serial block face SEM (SBFSEM), we visualized the outer surface morphology of the shell and generated 3D structures of the egg and larva during the hatching process. These images revealed that exposure to hatching-inducing bacteria catalyzed asymmetric degradation of the polar plugs prior to exit by the larva. Unrelated bacteria induced similar loss of electron density and dissolution of the structural integrity of the plugs. Egg hatching was most efficient when high densities of bacteria were bound to the poles. Consistent with the ability of taxonomically distant bacteria to induce hatching, additional results suggest chitinase released from larva within the eggs degrade the plugs from the inside instead of enzymes produced by bacteria in the external environment. These findings define at ultrastructure resolution the evolutionary adaptation of a parasite for the microbe-rich environment of the mammalian gut.


Cytokine and chemokine expression profiles in response to Mycobacterium tuberculosis stimulation are altered in HIV-infected compared to HIV-uninfected subjects with active tuberculosis.
Mycobacterium tuberculosis (Mtb) infects nearly 2 million people annually and is the most common cause of death in HIV-infected individuals. Tuberculosis (TB) diagnostics cater to HIV-uninfected individuals in non-endemic countries, are expensive, slow, and lack sensitivity for those most affected. Patterns of soluble immune markers from Mtb-stimulated immune cells are not well defined in HIV co-infection. We assessed immune differences between HIV-infected and HIV-uninfected individuals with active TB utilizing IFNγ-based QuantiFERON®-TB Gold In-Tube (QFT) testing in Nairobi, Kenya. Excess QFT supernatants were used to measure cytokine and chemokine responses by a 17-plex bead array. Mtb/HIV co-infected participants were significantly less likely to be QFT+ (47.2% versus 84.2% in the HIV-uninfected group), and demonstrated lower expression of all cytokines except for IFNα2. Receiver operator characteristic analyses identified IL-1α as a potential marker of co-infection. Among HIV-infected individuals, CD4+ T cell count correlated weakly with the expression of several analytes. Co-expression analysis highlighted differences in immune profiles between the groups. These data suggest that there is a unique and detectable Mtb-specific immune response in co-infection. A better understanding of Mtb immunology can translate into much needed immunodiagnostics with enhanced sensitivity in HIV-infected individuals, facilitating their opportunity to obtain live-saving treatment.


Presynaptic modulation of acetylcholine release from cardiac parasympathetic neurons.
Acetylcholine can be released from parasympathetic nerve endings in rat atria by 57 mM K+ depolarization or by electrical field stimulation. We have studied the presynaptic modulation of [3H]acetylcholine release from superfused rat atria prelabeled with [3H]choline. Exogenous acetylcholine and the specific muscarinic agonist oxotremorine inhibit the stimulation-induced overflow of [3H]acetylcholine into the superfusion medium. The half-maximal inhibitory concentration (IC50) of oxotremorine is 0.3 microM. The cholinesterase inhibitor neostigmine also decreases K+-stimulated [3H]acetylcholine overflow, whereas the muscarinic antagonist atropine enhances the overflow of [3H]acetylcholine. These data suggest that acetylcholine release in atria is modulated through negative feedback by the endogenous transmitter. The sympathetic adrenergic neurotransmitter norepinephrine and the neurohormone epinephrine also inhibit the overflow of [3H]acetylcholine by approximately 60%. The IC50 values for the inhibitory effects of these catecholamines are 6.3 and 2.2 microM, respectively. The inhibitory effect of norepinephrine is blocked by the alpha-adrenergic receptor antagonist yohimbine but not by the beta-adrenergic receptor antagonist propranolol. We suggest that presynaptic muscarinic and alpha-adrenergic receptors participate in the physiological and pharmacological control of cardiac parasympathetic activity.


Botulinum Neurotoxin Type-A for the Treatment of Atypical Odontalgia.
Atypical odontalgia (AO), a subform of persistent idiopathic facial pain, is defined as a continuous toothache in which a thorough examination reveals no dental pathology. AO is believed to be a neuropathic condition, given that some cases are preceded by dental procedures. Different topical and systemic medications have been used for the treatment of AO, but their effect is often unsatisfactory. The authors aimed to assess the effect and safety of botulinum neurotoxin type-A (BoNTA) in a series of patients with AO. Four patients with refractory AO (2 males and 2 females, aged 31-72) were treated with local injections of BoNTA to the painful area. BoNTA was injected at various sites into the gums, and two patients had additional injections in the hard palate or the upper lip. The total dose of BoNTA for each procedure was 15-30 U, and the total number of injection points was 6-12. The follow-up ranged from 6 to 20 months. Two patients received two cycles of BoNTA, while the remaining patients received three and five cycles each, respectively. All patients obtained significant relief with complete or almost complete reduction of pain. The analgesic effect was apparent after a latency period of 3-14 days, and the effect persisted for 2-6 months. There were no adverse events reported from any of the interventions. The responses to BoNTA injections in this series agree with those previously observed in neuropathic pain. BoNTA injections may be a safe and effective option for the treatment of AO.


Off-pump coronary artery bypass in a patient with the antiphospholipid syndrome.
Patients with antiphospholipid syndrome (APS) are prone to excessive postoperative morbidity and mortality after cardiovascular surgery because of its thromboembolic derangements. We present a case of coronary artery bypass grafting (CABG) in a patient with primary APS. He suffered from repetitive coronary occlusion after percutaneous transluminal coronary angioplasty (PTCA). Since his lupus anticoagulant level was found to be 217 s (normal, <50 s), he was diagnosed as the primary APS. He received steroid pulsation therapy with 1000 mg of prednisolone, double-filtration plasmapheresis (DFPP) and 50 mg of cyclophosphamide to attenuate the antibody activity. Four months after the last PTCA, he experienced chest pain and approximately 90% of stenosis in the left anterior descending (LAD) lesion was apparent, although the titer for the lupus anticoagulant was reduced to the normal range. He had drug allergy to ticlopidine hydrochloride and aspirin. Taken together, his disease was found to be resistant to these medical treatments, and surgical treatment was considered. Since cardiopulmonary bypass is known to exaggerate its coagulatory and fibrinolytic complications, off-pump CABG (OPCAB) was feasible in this case. The left internal thoracic artery (ITA) was anastomosed to the LAD using the off-pump technique. The procedure was successful, and the postoperative course for 3 years has been satisfactory without any cardiovascular complaints.


Microbiota-Meditated Immunity Abnormalities Facilitate Hepatitis B Virus Co-Infection in People Living With HIV: A Review.
Hepatitis B virus (HBV) co-infection is fairly common in people living with HIV (PLWH) and affects millions of people worldwide. Identical transmission routes and HIV-induced immune suppression have been assumed to be the main factors contributing to this phenomenon. Moreover, convergent evidence has shown that people co-infected with HIV and HBV are more likely to have long-term serious medical problems, suffer more from liver-related diseases, and have higher mortality rates, compared to individuals infected exclusively by either HIV or HBV. However, the precise mechanisms underlying the comorbid infection of HIV and HBV have not been fully elucidated. In recent times, the human gastrointestinal microbiome is progressively being recognized as playing a pivotal role in modulating immune function, and is likely to also contribute significantly to critical processes involving systemic inflammation. Both antiretroviral therapy (ART)-naïve HIV-infected subjects and ART-treated individuals are now known to be characterized by having gut microbiomic dysbiosis, which is associated with a damaged intestinal barrier, impaired mucosal immunological functioning, increased microbial translocation, and long-term immune activation. Altered microbiota-related products in PLWH, such as lipopolysaccharide (LPS) and short-chain fatty acids (SCFA), have been associated with the development of leaky gut syndrome, favoring microbial translocation, which in turn has been associated with a chronically activated underlying host immune response and hence the facilitated pathogenesis of HBV infection. Herein, we critically review the interplay among gut microbiota, immunity, and HIV and HBV infection, thus laying down the groundwork with respect to the future development of effective strategies to efficiently restore normally diversified gut microbiota in PLWH with a dysregulated gut microbiome, and thus potentially reduce the prevalence of HBV infection in this population.


A Quality by Design Approach to Developing and Manufacturing Polymeric Nanoparticle Drug Products.
The translation of nanomedicines from concepts to commercial products has not reached its full potential, in part because of the technical and regulatory challenges associated with chemistry, manufacturing, and controls (CMC) development of such complex products. It is critical to take a quality by design (QbD) approach to developing nanomedicines-using a risk-based approach to identifying and classifying product attributes and process parameters and ultimately developing a deep understanding of the products, processes, and platform. This article exemplifies a QbD approach used by BIND Therapeutics, Inc., to industrialize a polymeric targeted nanoparticle drug delivery platform. The focus of the approach is on CMC affairs but consideration is also given to preclinical, clinical, and regulatory aspects of pharmaceutical development. Processes are described for developing a quality target product profile and designing supporting preclinical studies, defining critical quality attributes and process parameters, building a process knowledge map, and employing QbD to support outsourced manufacturing.


Mixing and reaction kinetics in porous media: an experimental pore scale quantification.
We propose a new experimental set up to characterize mixing and reactive transport in porous media with a high spatial resolution at the pore scale. The analogous porous medium consists of a Hele-Shaw cell containing a single layer of cylindrical solid grains built by soft lithography. On the one hand, the measurement of the local, intrapore, conservative concentration field is done using a fluorescent tracer. On the other hand, considering a fast bimolecular reaction A + B → C occurring as A displaces B, we quantify the rate of product formation from the spatially resolved measurement of the pore scale reaction rate, using a chemiluminescent reaction. The setup provides a dynamical measurement of the local concentration field over 3 orders of magnitude and allows investigating a wide range of Péclet and Damköhler numbers by varying the flow rate within the cell and the local reaction rate. We use it to study the kinetics of the reaction front between A and B. While the advection-dispersion (Fickian) theory, applied at the continuum scale, predicts a scaling of the cumulative mass of product C as MC ∝ √t, the experiments exhibit two distinct regimes in which the produced mass MC evolves faster than the Fickian behavior. In both regimes the front rate of product formation is controlled by the geometry of the mixing interface between the reactants. Initially, the invading solute is organized in stretched lamellae and the reaction is limited by mass transfer across the lamella boundaries. At longer times the front evolves into a second regime where lamellae coalesce and form a mixing zone whose temporal evolution controls the rate of product formation. In this second regime, the produced mass of C is directly proportional to the volume of the mixing zone defined from conservative species. This interesting property is indeed verified from a comparison of the reactive and conservative data. Hence, for both regimes, the direct measurement of the spatial distribution of the pore scale reaction rate and conservative component concentration is shown to be crucial to understanding the departure from the Fickian scaling as well as quantifying the basic mechanisms that govern the mixing and reaction dynamics at the pore scale.


Effect of naturally occurring triterpenoids glycyrrhizic acid, ursolic acid, oleanolic acid and nomilin on the immune system.
The effect of naturally occurring triterpenoid compounds such as glycyrrhizic acid, ursolic acid, oleanolic acid, and nomilin on the immune system was studied using Balb/c mice. Intraperitoneal treatments with 5 doses of these terpenoid compounds were found to enhance the total white blood cells (WBC) count. In ursolic acid, oleanolic acid and nomilin treated animals the maximum total WBC count was observed on the 6th day, while in glycyrrhizic acid treated animals it was observed only on the 9th day after the drug treatment. In ursolic acid, oleanolic acid and nomilin treated animals the percentage of increase in the total WBC count was to 91.48 +/- 4.6%, 135.75 +/- 6.4% and 117.33 +/- 17.9% respectively. In the glycyrrhizic acid treated animals the total WBC count was increased to 114.9 +/- 18%. Bone marrow cellularity and alpha-esterase positive cells were also enhanced by the treatment with these terpenoids. Treatment with various triterpenoids along with antigen produced an enhancement in the specific antibody titre and the number of plaque forming cells (PFC) in the spleen. Triterpenoids remarkably inhibited delayed type hypersensitivity reaction (DTH). These results indicate the immunomodulatory activity of naturally occurring triterpenoids such as glycyrrhizic acid, ursolic acid, oleanolic acid and nomilin.


Functional Characterization of A Deformed Epidermal Autoregulatory Factor 1 Gene in Litopenaeus vannamei.
Innate immunity is crucial for invertebrate defense against pathogenic infections. Numerous studies have indicated that the Toll-NF-κB pathway plays an important role in this process, particularly in anti-bacterial and anti-fungal immunity. Although the function of this pathway has been studied extensively, there are still uncertainties regarding its role in shrimp. In this study, we investigated the functions of Deformed Epidermal Autoregulatory Factor 1 (LvDEAF1) in Litopenaeus vannamei, a member of the Toll-NF-κB pathway. Our findings revealed that LvDEAF1 interacts with L. vannamei Pellino1 (LvPellino1). LvDEAF1 enhances the promoter activity of certain antimicrobial peptide genes, such as Metchnikowin and Drosomycin, in Drosophila Schneider 2 (S2) cells by binding to the NF-κB binding site. LvDEAF1 and LvPellino1 exhibit positive and synergistic effects. Additionally, the expression of LvDEAF1 is induced by Vibrio parahaemolyticus infection and lipopolysaccharides or zymosan treatment. Knockdown LvDEAF1 expression resulted in a decrease in Penaeidins 4 expression and an increase in the cumulative mortality of shrimp infected with V. parahaemolyticus. These findings indicate that LvDEAF1 plays an important role in the Toll-NF-κB pathway of L. vannamei and is essential for its immune response against pathogens.


Simple time-saving method for iron determination based on fluorescence quenching of an azaflavanon-3-ol compound.
A simple and time-saving spectrofluorometric method developed using an azaflavanon-3-ol compound was used for the determination of iron in various food samples. Nitric acid and hydrogen peroxide were used for digestion of samples in a closed microwave system. The method was validated by analyzing two certified reference materials (CRM-SA-C Sandy Soil C and Mixed Polish Herbs INCT-MPH-2). Measurements were carried out using a modified standard addition method. The standard addition graph was linear until 21.6 mg/L in the determination of iron(III). Detection and quantification limits were 0.81 and 2.4 mg/L, respectively. Satisfactory accuracy was obtained for spinach, dill, mint, purslane, rocket, red lentils, dry beans, and two iron medicinal tablets. High recoveries were found for streamwater samples fortified at three different concentrations. The method is simple, time-saving, cost-effective, and suitable for the determination of the iron content of foods.


Assessing household lifestyle exposures from consumer purchases, the My Purchases cohort.
Consumer purchase data (CPD) is a promising instrument to assess the impact of purchases on health, but is limited by the need for manual scanning, a lack of access to data from multiple retailers, and limited information on product data and health outcomes. Here we describe the My Purchases cohort, a web-app enabled, prospective collection of CPD, covering several large retail chains in Denmark, that enables linkage to health outcomes. The cohort included 459 participants as of July 03, 2023. Up to eight years of CPD have been collected, with 2,225,010 products purchased, comprising 223,440 unique products. We matched 88.5% of all products by product name or item number to one generic food database and three product databases. Combined, the databases enable analysis of key exposures such as nutrients, ingredients, or additives. We found that increasing the number of retailers that provide CPD for each consumer improved the stability of individual CPD profiles and when we compared kilojoule information from generic and specific product matches, we found a median modified relative difference of 0.23. Combined with extensive product databases and health outcomes, CPD could provide the basis for extensive investigations of how what we buy affects our health.


Chronic fatigue syndrome among overseas development workers: A qualitative study.
A relatively high proportion of overseas development workers may develop chronic fatigue syndrome (CFS). A qualitative study was conducted in order to investigate how such people perceived their condition. Twelve people who had developed CFS while working overseas with development organizations, or shortly after visiting development projects, were interviewed about their experiences. Their responses were analyzed using a grounded theory approach. Most of the participants considered themselves to have been extremely healthy before they developed CFS. The syndrome did not appear to have been caused by depression. The symptoms which were reported covered the range of symptoms typically found in studies of CFS. Respondents described difficulty in receiving, and accepting, a diagnosis. All of the participants attributed the CFS to multiple causes, the principal causes being overwork, stress and infections. Among the consequences of CFS reported to be the most difficult were having to leave the development project prematurely; pain; powerlessness; loss of independence, and the unpredictability of CFS. Factors which had helped respondents cope with these difficulties included religious beliefs; comparisons with people who were worse off than they were; thinking about positive consequences of the condition, and talking with supportive people. Some theories have suggested that CFS symptoms arise as a result of depression or other emotional difficulties, which the individual is not able to acknowledge. The results indicated that such theories may not apply to this subgroup of people with CFS. Further research on the etiology of CFS is warranted. Respondents described high levels of work-related stress as common to the experience of development work. It might be beneficial to train development workers in stress management techniques. Development organizations should be encouraged to ensure that their workers take sufficient time to rest, and attempts should be made to reduce work pressures.


Urinary DEHP metabolites and fasting time in NHANES.
Exposure assessment analyses conducted in Europe have concluded that the primary pathway of exposure to di(2-ethylhexyl) phthalate (DEHP) is through the diet. The purpose of this study is to evaluate whether urinary DEHP metabolite data from the 2007-2008 National Health and Nutritional Examination Survey (NHANES) demonstrate relationships with reported food-fasting time consistent with diet as the predominant exposure pathway. Previous controlled-dosing data demonstrate that DEHP metabolite concentrations in urine first rise and then decline over time, with first-order elimination becoming evident at about 6 h post exposure. Regression of the concentrations of four key DEHP metabolites vs reported fasting times between 6 and 18 h in adults resulted in apparent population-based urinary elimination half-lives, consistent with those previously determined in a controlled-dosing experiment, supporting the importance of the dietary pathway for DEHP. For fasting times less than about 6 h, sampling session (morning, afternoon, or evening) affected the measured metabolite concentrations. Evening samples showed the highest metabolite concentrations, supporting a hypothesis of recent daily dietary exposures from multiple meals, whereas morning and afternoon samples for fasting times less than 6 h were similar and somewhat lower than evening samples, consistent with less-substantial early day dietary exposure. Variations in children's bodyweight-normalized creatinine excretion and food intake rates contribute to a strong inverse relationship between urinary DEHP metabolite concentrations and age under age 18. Finally, a previously published pharmacokinetic model for DEHP demonstrates that time since previous urinary void, a parameter not measured in NHANES, is predicted to result in non-random effects on measured urinary concentrations.


Phytotoxic and Antimicrobial Terrein Derivatives and Butenolides Isolated from the Endophytic Fungus Aspergillus terreus HT5.
Two new terrein derivatives, aspergilethers A and B (1 and 2), two known analogues (3 and 4), and three known butenolides (5-7) were isolated from the endophyte Aspergillus terreus HT5. Their structures were determined by spectroscopic analysis and ECD and NMR calculations. Interestingly, 1 and 2 had unpresented medium aliphatic side chains in terrein derivatives, with different absolute configurations at C-7, which was very scarce. (+)-Terrein (3) exhibited potent postemergence phytotoxicity toward Amaranthaceae, Portulacaceae, and Fabaceae, with MIC values of 250-1000 μg/mL. Transcriptome analysis and qRT-PCR suggested that (+)-terrein induced the transcriptional expression of aging-related genes to accelerate organ senescence and stimulated plant detoxification response. The conjugated system between keto carbonyl and double bonds in the cyclopentenone ring and side chain, and the configurations of C-2 and C-3, played critical roles in the phytotoxicity of terrein derivatives. Meanwhile, 3 was first reported to display moderate antioomycetes activity toward Phytophthora nicotiana.


The effect of two ammonia-emission-reducing pig housing systems on odour emission.
Odour nuisance from agricultural activities is increasing in densely populated countries like the Netherlands. To develop adequate regulations, a large-scale, government-financed monitoring programme was started in the mid-1990s to establish odour emission levels for both conventional and low ammonia emission housing systems for cattle, pigs and poultry. The results indicate that high- and low-odour emission housing are difficult to distinguish because of the large variation within housing systems. Measurements on different farm locations within the same housing system show both a large variation between locations and within one location (in time). The latter, however, is significantly smaller, which suggests that farm management is an important determinant in odour emission that interferes with the effects of housing systems. The current research was aimed at determining the effect of two common ammonia-reducing pig-housing systems on odour emissions compared to conventional housing systems under similar management conditions. The respective reduction principles of these systems are reducing the emitting surface of the manure pit and cooling of manure in the manure pit (both pits beneath slatted floor). Five farms that combined conventional housing with one low-ammonia system (three reduced emitting surface and two manure cooling) were selected for a direct, pair-wise comparison of (olfactometric) odour emission measurements. The results show a highly significant effect (p < 0.01) for two of the three reduced emitting surface systems and for one of the two manure cooling system. The average odour reduction percentages of these systems are 35% (from 24.9 to 16.0 OUE/s per animal) and 23% (from 30.1 to 24.0 OUE/s per animal) respectively. Although odour emission reduction through the type of housing system is possible, management factors interact with the system and thereby determine whether the system reduces odour emission or not.


Ability of Dentists and Students to Detect Caries by Using the International Caries Detection and Assessment System.
To evaluate the ability of dentists and dental students to detect caries by using the International Caries Detection and Assessment System (ICDAS). A cross-sectional study was conducted in Riyadh city and in the College of Dentistry at King Saud University (KSU) in Saudi Arabia. The study sample included a cluster sampling of 50 private clinics (100 dentists) and all 3rd-, 4th-, and 5th-year students (393 students). Data were collected using an electronic questionnaire. The ability score of detecting caries for each group was identified by calculating the mean percentages of the score. The data were entered into SPSS Version 20. One-way ANOVA was used for comparing quantitative data. The overall response rate of the survey was 64.5% (318/493). A total of 62.6% (199) of respondents know about ICDAS. All groups had difficulty assessing the activity of caries in Code 2. There were significant differences among all groups in the ability to detect caries (P-value: 0:00). Moreover, 4th- and 5th-year students had the highest mean of percentage ability score (53.8% and 57.6%, respectively) to detect caries using ICDAS compared to 3rd-year students and general practitioners (38.6% and 38.7%, respectively). Overall, detection of early dental caries limited to enamel was confusing and difficult. The abilities of dentists and dental students to detect caries using ICDAS were low and require improvement by continuing further clinical training.


Astrocyte Activation via Stat3 Signaling Determines the Balance of Oligodendrocyte versus Schwann Cell Remyelination.
Remyelination within the central nervous system (CNS) most often is the result of oligodendrocyte progenitor cells differentiating into myelin-forming oligodendrocytes. In some cases, however, Schwann cells, the peripheral nervous system myelinating glia, are found remyelinating demyelinated regions of the CNS. The reason for this peripheral type of remyelination in the CNS and what governs it is unknown. Here, we used a conditional astrocytic phosphorylated signal transducer and activator of transcription 3 knockout mouse model to investigate the effect of abrogating astrocyte activation on remyelination after lysolecithin-induced demyelination of spinal cord white matter. We show that oligodendrocyte-mediated remyelination decreases and Schwann cell remyelination increases in lesioned knockout mice in comparison with lesioned controls. Our study shows that astrocyte activation plays a crucial role in the balance between Schwann cell and oligodendrocyte remyelination in the CNS, and provides further insight into remyelination of CNS axons by Schwann cells.


Cell-free protein production of a gamma secretase homolog.
Cleavage of the transmembrane domain (TMD) of amyloid-β precursor protein (APP) by γ-secretase, an intramembrane aspartyl protease, generates Aβ peptides of various lengths that form plaques in the brains of Alzheimer's disease patients. Although the debate has not been finally resolved whether these plaques trigger the onset of Alzheimer's or are side products, disease-related mutations suggest their implication in the etiology of the dementia. These occur both in presenilin, the catalytic subunit of γ-secretase, and in the TMD of APP. Despite two seminal cryo-electron microscopy structures that show the complex of γ-secretase with its substrates APP and Notch, the mechanism of γ-secretase is not yet fully understood. Especially on which basis it selects its substrates is still an enigma. The presenilin homolog PSH from the archaeon Methanoculleus marisnigri JR1 (MCMJR1) is catalytically active without accessory proteins in contrast to γ-secretase making it an excellent model for studies of the basic cleavage process. We here focused on the cell-free expression of PSH screening a range of conditions. Cleavage assays to verify the activity show that not only the yield, but mainly the activity of the protease depends on the careful selection of expression conditions. Optimal results were found for a cell-free expression at relatively low temperature, 20 °C, employing cell lysates prepared from E. coli Rosetta cells. To speed up protein preparation for immediate functional assays, a crude purification protocol was developed. This allows to produce ready-made PSH in a fast and efficient manner in less than two days.


The "balance of nature"-evolution of a Panchreston.
The earliest concept of a balance of nature in Western thought saw it as being provided by gods but requiring human aid or encouragement for its maintenance. With the rise of Greek natural philosophy, emphasis shifted to traits gods endowed species with at the outset, rather than human actions, as key to maintaining the balance. The dominance of a constantly intervening God in the Middle Ages lessened interest in the inherent features of nature that would contribute to balance, but the Reformation led to renewed focus on such features, particularly traits of species that would maintain all of them but permit none to dominate nature. Darwin conceived of nature in balance, and his emphasis on competition and frequent tales of felicitous species interactions supported the idea of a balance of nature. But Darwin radically changed its underlying basis, from God to natural selection. Wallace was perhaps the first to challenge the very notion of a balance of nature as an undefined entity whose accuracy could not be tested. His skepticism was taken up again in the 20th century, culminating in a widespread rejection of the idea of a balance of nature by academic ecologists, who focus rather on a dynamic, often chaotic nature buffeted by constant disturbances. The balance-of-nature metaphor, however, lives on in large segments of the public, representing a fragile aspect of nature and biodiversity that it is our duty to protect.


How landscape scale changes affect ecological processes in conservation areas: external factors influence land use by zebra (Equus burchelli) in the Okavango Delta.
Most large-bodied wildlife populations in sub-Saharan Africa only survive in conservation areas, but are continuing to decline because external changes influence ecological processes within reserves, leading to a lack of functionality. However, failure to understand how landscape scale changes influence ecological processes limits our ability to manage protected areas. We used GPS movement data to calculate dry season home ranges for 14 zebra mares in the Okavango Delta and investigated the effects of a range of landscape characteristics (number of habitat patches, mean patch shape, mean index of juxtaposition, and interspersion) on home range size. Resource utilization functions (RUF) were calculated to investigate how specific landscape characteristics affected space use. Space use by all zebra was clustered. In the wetter (Central) parts of the Delta home range size was negatively correlated with the density of habitat patches, more complex patch shapes, low juxtaposition of habitats and an increased availability of floodplain and grassland habitats. In the drier (Peripheral) parts of the Delta, higher use by zebra was also associated with a greater availability of floodplain and grassland habitats, but a lower density of patches and simpler patch shapes. The most important landscape characteristic was not consistent between zebra within the same area of the Delta, suggesting that no single foraging strategy is substantially superior to others, and so animals using different foraging strategies may all thrive. The distribution and complexity of habitat patches are crucial in determining space use by zebra. The extent and duration of seasonal flooding is the principal process affecting habitat patch characteristics in the Okavango Delta, particularly the availability of floodplains, which are the habitat at greatest risk from climate change and anthropogenic disturbance to the Okavango's catchment basin. Understanding how the factors that determine habitat complexity may change in the future is critical to the conservation of large mammal populations. Our study shows the importance of maintaining flood levels in the Okavango Delta and how the loss of seasonal floodplains will be compounded by changes in habitat configuration, forcing zebra to change their relative space use and enlarge home ranges, leading to increased competition for key resources and population declines.


Vascular tumors of the hand and forearm.
Although blood vessel tumors are rare, they are frequently encountered in the hand and forearm, being the fourth most common tumor of the hand. The treating physician should be aware of the acquired, traumatic, and congenital vascular tumors that are so prevalent in this area.


Less healthy dietary pattern is associated with smoking in Korean men according to nationally representative data.
The relationship between smoking and nutrient intake has been widely investigated in several countries. However, Korea presents a population with a smoking rate of approximately 50% and dietary consumption of unique foods. Thus, the aim of this study was to evaluate the association of dietary patterns with smoking in Korean men using a nationally representative sample. The study subjects were comprised of 4,851 Korean men over 19 yr of age who participated in the fourth Korean National Health and Nutrition Examination Survey. Dietary data were assessed by the 24-hr recall method. The smoking group comprised 2,136 men (46.6%). Five dietary patterns were derived using factor analysis: 'sugar & fat', 'vegetables & seafood', 'meat & drinks', 'grains & eggs', and 'potatoes, fruits and dairy products.' Current smokers showed a more significant 'sugar & fat' pattern (P = 0.001) while significantly less of the 'vegetables & seafood' and 'potatoes, fruits and dairy products' patterns (P = 0.011, P < 0.001, respectively). As found in similar results from Western studies, Korean male smokers showed less healthy dietary patterns than nonsmokers. Thus, the result of this study underlines the need for health professionals to also provide advice on dietary patterns when counseling patients on smoking cessation.


Non-progressive central core disease with severe congenital scoliosis: a case report.
An extremely unusual case of central core disease combined with a congenital spine deformity is described. The congenital myopathy was non-progressive, but the scoliotic curve worsened markedly. This case was characterised also by the type of squatting ambulation the child used until the age of 12, when the limb contractures were corrected surgically and with casting, permitting her to walk in an upright position. It was not feasible to perform spinal surgery.


Variations in brain defects result from cellular mosaicism in the activation of heat shock signalling.
Repetitive prenatal exposure to identical or similar doses of harmful agents results in highly variable and unpredictable negative effects on fetal brain development ranging in severity from high to little or none. However, the molecular and cellular basis of this variability is not well understood. This study reports that exposure of mouse and human embryonic brain tissues to equal doses of harmful chemicals, such as ethanol, activates the primary stress response transcription factor heat shock factor 1 (Hsf1) in a highly variable and stochastic manner. While Hsf1 is essential for protecting the embryonic brain from environmental stress, excessive activation impairs critical developmental events such as neuronal migration. Our results suggest that mosaic activation of Hsf1 within the embryonic brain in response to prenatal environmental stress exposure may contribute to the resulting generation of phenotypic variations observed in complex congenital brain disorders.


A mathematical model for simulating the phase-based transmissibility of a novel coronavirus.
As reported by the World Health Organization, a novel coronavirus (2019-nCoV) was identified as the causative virus of Wuhan pneumonia of unknown etiology by Chinese authorities on 7 January, 2020. The virus was named as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) by International Committee on Taxonomy of Viruses on 11 February, 2020. This study aimed to develop a mathematical model for calculating the transmissibility of the virus. In this study, we developed a Bats-Hosts-Reservoir-People transmission network model for simulating the potential transmission from the infection source (probably be bats) to the human infection. Since the Bats-Hosts-Reservoir network was hard to explore clearly and public concerns were focusing on the transmission from Huanan Seafood Wholesale Market (reservoir) to people, we simplified the model as Reservoir-People (RP) transmission network model. The next generation matrix approach was adopted to calculate the basic reproduction number (R0) from the RP model to assess the transmissibility of the SARS-CoV-2. The value of R0 was estimated of 2.30 from reservoir to person and 3.58 from person to person which means that the expected number of secondary infections that result from introducing a single infected individual into an otherwise susceptible population was 3.58. Our model showed that the transmissibility of SARS-CoV-2 was higher than the Middle East respiratory syndrome in the Middle East countries, similar to severe acute respiratory syndrome, but lower than MERS in the Republic of Korea.


Taste receptor signalling - from tongues to lungs.
Taste buds are the transducing endorgans of gustation. Each taste bud comprises 50-100 elongated cells, which extend from the basal lamina to the surface of the tongue, where their apical microvilli encounter taste stimuli in the oral cavity. Salts and acids utilize apically located ion channels for transduction, while bitter, sweet and umami (glutamate) stimuli utilize G-protein-coupled receptors (GPCRs) and second-messenger signalling mechanisms. This review will focus on GPCR signalling mechanisms. Two classes of taste GPCRs have been identified, the T1Rs for sweet and umami (glutamate) stimuli and the T2Rs for bitter stimuli. These low affinity GPCRs all couple to the same downstream signalling effectors that include Gβγ activation of phospholipase Cβ2, 1,4,5-inositol trisphosphate mediated release of Ca(2+) from intracellular stores and Ca(2+) -dependent activation of the monovalent selective cation channel, TrpM5. These events lead to membrane depolarization, action potentials and release of ATP as a transmitter to activate gustatory afferents. The Gα subunit, α-gustducin, activates a phosphodiesterase to decrease intracellular cAMP levels, although the precise targets of cAMP have not been identified. With the molecular identification of the taste GPCRs, it has become clear that taste signalling is not limited to taste buds, but occurs in many cell types of the airways. These include solitary chemosensory cells, ciliated epithelial cells and smooth muscle cells. Bitter receptors are most abundantly expressed in the airways, where they respond to irritating chemicals and promote protective airway reflexes, utilizing the same downstream signalling effectors as taste cells.


DRO1 inactivation drives colorectal carcinogenesis in ApcMin/+ mice.
Colorectal cancer develops from adenomatous precursor lesions by a multistep process that involves several independent mutational events in oncogenes and tumor suppressor genes. Inactivation of the adenomatous polyposis coli (APC) tumor suppressor gene is an early event and a prerequisite for the development of human colorectal adenoma. Previous in vitro studies identified DRO1 (CCDC80) to be a putative tumor suppressor gene that is negatively regulated in colorectal cancers and downregulated upon neoplastic transformation of epithelial cells. To investigate the in vivo role of DRO1 in colorectal carcinogenesis, a constitutive DRO1 knockout mouse model was generated. Disruption of DRO1 did not result in spontaneous intestinal tumor formation, consistent with the notion that DRO1 might have a role in suppressing the development of colon tumors in Apc(Min) (/+) mice, a widely used model for studying the role of APC in intestinal tumorigenesis that is hampered by the fact that mice predominantly develop adenomas in the small intestine and not in the colon. Here, deletion of DRO1 in Apc(Min) (/+) mice results in earlier death, a dramatically increased colonic tumor burden, and frequent development of colorectal carcinoma. Furthermore, enhanced phosphorylation of ERK1/2 is observed in colon epithelium and tumors from DRO1 knockout mice. Thus, this study reveals that inactivation of DRO1 is required for colorectal carcinogenesis in the Apc(Min) (/+) mouse and establishes a new mouse model for the study of colorectal cancer. This report characterizes a new mouse model for the study of colorectal cancer and establishes DRO1 (CCDC80) as a tumor suppressor via a mechanism involving ERK phosphorylation.


Trajectories after first-episode psychosis: Complement to ambiguous outcomes of long-term antipsychotic treatment by exploring a few hidden cases.
Patient's long-term phenomenology after first-episode psychosis could be blurred due to early intervention. The contradictory messages regarding necessity of long-term antipsychotic treatment derived from different methodologies warrants careful reappraisal. We approached a group of patients lost to follow-up in a previous study. Targeting these 44 missing patients, we sent 2 carefully worded letters to invite them for interviews to see if their life trajectories were different from those who stayed in a university-based hospital system. A total of 21 patients replied, but only 8 agreed to in-depth interviews. Of these, 2 warranted revision of their diagnoses as there had been no recurrence of psychotic symptoms and they had remained antipsychotic-free for several years despite displaying a dysthymic state; 1 fulfilled remission criteria on intermittent low-dose antipsychotics but kept a distance from any potential stressor; 1 achieved full remission with good functioning and discontinued medications for a year, but resumed taking antipsychotics after feeling an impending relapse; the other 4 showed common courses of chronic schizophrenia with repeated admission and/or rehabilitation programs in other service systems. The trajectories after first-episode psychosis should not be over-simplified by calculating the probability of relapse or the odds of achieving adequate functioning determined by medication adherence or not. Examining from a dynamic perspective employing a qualitative approach to take into account diagnostic stability, treatment preferences, psychosocial factors, individual coping strategies and personalized formulation of illness, we can gain more insight into the ambiguous information revealed by the recent literature.


Thyroid function abnormalities in HIV-infected patients.
Abnormal thyroid function test results are common among human immunodeficiency virus (HIV)-infected patients. Although the prevalence of overt thyroid disease does not appear to be significantly increased in HIV-infected patients, compared with the general population, specific patterns of abnormal thyroid function test findings are more frequently identified among HIV-infected patients. Among patients with advanced acquired immunodeficiency syndrome, nonthyroidal illness (i.e., euthyroid sick syndrome) is common. During antiretroviral therapy, the prevalence of 2 generally asymptomatic conditions (subclinical hypothyroidism, which is characterized by isolated elevated thyroid-stimulating hormone levels, and isolated low free thyroxine levels) is increased. In addition, Graves disease, which is marked by low thyroid-stimulating hormone and elevated thyroxine levels, may occur during immune reconstitution. Testing for thyroid disease among symptomatic patients should begin with measurement of the thyroid-stimulating hormone level. However, there is insufficient evidence to recommend routine thyroid screening of asymptomatic HIV-infected individuals. This review summarizes the current evidence regarding the optimal laboratory evaluation of thyroid function; highlights the causes, presentation, and treatment of thyroid dysfunction in HIV-infected patients; and discusses the controversies regarding screening.


Luminal endothelial lectins with affinity for N-acetylglucosamine determine flow-induced cardiac and vascular paracrine-dependent responses.
Coronary blood flow applied to the endothelial lumen modulates parenchymal functions via paracrine effectors, but the mechanism of flow sensation is unknown. We and others have demonstrated that coronary endothelial luminal membrane (CELM) oligosaccharides and lectins are involved in flow detection, and we proposed that cardiac effects of coronary flow result from a reversible flow-modulated lectin-oligosaccharide interaction. Recently, glycosylated and amiloride-sensitive Na(+)/Ca(++) channels (ENaCs) have been proposed to be involved in the flow-induced endothelial responses. Because N-acetylglucosamine (GlcNac) is one of the main components of glycocalyx oligosaccharides (i.e., hyaluronan [-4GlcUAbeta1-3GlcNAcbeta1-](n)), the aim of this article is to isolate and define CELM GlcNac-binding lectins and determine their role in cardiac and vascular flow-induced effects. For this purpose, we synthesized a 460-kDa GlcNac polymer (GlcNac-Pol) with high affinity toward GlcNac-recognizing lectins. In the heart, intracoronary administration of GlcNac-Pol upon binding to CELM diminishes the flow-dependent positive inotropic and dromotropic effects. Furthermore, GlcNac-Pol was used as an affinity probe to isolate CELM GlcNac-Pol-recognizing lectins and at least 35 individual lectinic peptides were identified, one of them the beta-ENaC channel. Some of these lectins could participate in flow sensing and in GlcNac-Pol-induced effects. We also adopted a flow-responsive and well-accepted model of endothelial-parenchymal paracrine interaction: isolated blood vessels perfused at controlled flow rates. We established that flow-induced vasodilatation (FIV) is blocked by endothelial luminal membrane (ELM) bound GlcNac-Pol, nitro-l-arginine methyl ester and indomethacin, amiloride, and hyaluronidase. The effect of hyaluronidase was reversed by infusion of soluble hyaluronan. These results indicate that GlcNac-Pol inhibits FIV by competing and displacing intrinsic hyaluronan bound to a lectinic structure such as the amiloride-sensitive ENaC. Nitric oxide and prostaglandins are the putative paracrine mediators of FIV.


Self-assembled magnetic heterostructure of Co/DLC films.
In order to adapt to the quick and large amount of necessity in data flow for 5G cloud generation, it is necessary to develop a technology of warm storage device in market which takes a great balance between the reading/writing performance and the price per storage capacity. The technologies of warm storage devices are assumed to adopt phase change memory (PCM), resistive random access memory or magnetoresistive random access memory which have the highest possibilities to 5G structures and magnetic properties of Co on non-hydrogenated diamond like carbon (DLC)/Si(100) films and Co/DLC interface are investigated. The self-assembled magnetic heterostructure is firstly reported in hexagonal close packing Co layers perpendicular magnetic anisotropy (PMA) on Co carbide layers (in-plane) during Co deposited on DLC/Si(100). A PMA/in-plane magnetic heterostructure is expected to have the highest switching current to the energy barrier ratio of near 4 in previous report, which has great potential for developing warm memory devices. Based on these unique characteristics, we provide a novel design called magnetic anisotropy-phase change memory (Mani-PCM) which can impact the developing blueprint of memory. The working process of Mani-PCM includes in set, reset and read states as a universal PCM. This brand new technology is highly promising as warm memory devices including high reading/writing performance and economical price per storage capacity.


The predictive value of ABCB1, ABCG2, CYP3A4/5 and CYP2D6 polymorphisms for risperidone and aripiprazole plasma concentrations and the occurrence of adverse drug reactions.
We investigated in ninety Caucasian pediatric patients the impact of the main polymorphisms occurring in CYP3A, CYP2D6, ABCB1 and ABCG2 genes on second-generation antipsychotics plasma concentrations, and their association with the occurrence of adverse drug reactions. Patients with the CA/AA ABCG2 genotype had a statistically significant lower risperidone plasma concentration/dose ratio (Ct/ds) (P-value: 0.007) and an higher estimated marginal probability of developing metabolism and nutrition disorders as compared to the ABCG2 c.421 non-CA/AA genotypes (P-value: 0.008). Multivariate analysis revealed that the ABCG2 c.421 CA/AA genotype was found associated to a higher hazard (P-value: 0.004) of developing adverse drug reactions classified as metabolism and nutrition disorders. The ABCB1 2677TT/3435TT genotype had a statistically significant lower aripiprazole Ct/ds if compared with patients with others ABCB1 genotypes (P-value: 0.026). Information obtained on ABCB1 and ABCG2 gene variants may result useful to tailor treatments with these drugs in Caucasian pediatric patients.


[Significances of health and ways of taking care of oneself prepared by male frequenters of Basic Health Units - UBS].
The research sought to understand the significances of health and ways of taking care of oneself prepared by male frequenters of a Basic Health Unit - UBS in Manaus. The method used was qualitative research through semi-structured interviews with male frequenters and healthcare professionals of a UBS located in the outskirts of Manaus in the state of Amazonas. Data were analyzed using techniques of Thematization, Content Analysis and Significance Processing based on the Social Constructivist approach proposed by Spink. The research revealed the multifaceted issues of gender, which show that men "are not all equal," as there are various types of masculinities. The men interviewed in the health service showed that there are significances of health that they share with each other, but they also differ in many dimensions. The survey reflected that the plurality of significances of health and the ways of taking care of oneself confer a human character upon health and claim the proactive role of frequenters in the construction of a system of comprehensive health care. They point to indicators that can contribute to interventions in health for increasing the visibility of men in the health services and consequently the ability of the services to deal with them.


CNS granulomatosis in a child with chronic granulomatous disease.
Chronic granulomatous disease (CGD) is a disease in which a granulomatous process involves various organ systems and in which recurrent infections are seen. The basic defect is the absence of the granulocyte respiratory burst. CNS involvement is rare. We present a report of a child with CGD and CNS involvement, presenting with hydrocephalus. Candida was identified in the granulomata. The patient responded well to a CSF shunt and antifungal therapy.


[Chronic obstructive pulmonary disease: risk and benefit of testosterone therapy].
Muscular wasting is frequently encountered in COPD patients and is related to a decrease in exercise tolerance, a higher morbidity and mortality. One of the potential causes isa low serum testosterone, which is frequent in COPD. Various studies have explored the effect of testosterone administration alone or as part of combined pulmonary rehabilitation and nutrition protocols. Testosterone had a positive impact on muscle mass and force, and to a lesser extent on physical endurance and respiratory parameters. Future studies should better define appropriate dosage and treatment duration. In the meantime, testosterone should be administered to COPD patients with overt hypogonadism, or in multidisciplinary specialized programmes.


Initial incursion of pandemic (H1N1) 2009 influenza A virus into European pigs.
The initial incursion of pandemic (H1N1) 2009 influenza A virus (pH1N1) into a European pig population is reported. Diagnosis of swine influenza caused by pandemic virus was made during September 2009 following routine submission of samples for differential diagnosis of causative agents of respiratory disease, including influenza A virus. All four pigs (aged six weeks) submitted for investigation from a pig herd of approximately 5000 animals in Northern Ireland, experiencing acute-onset respiratory signs in finishing and growing pigs, were positive by immunofluorescence for influenza A. Follow-up analysis of lung tissue homogenates by real-time RT-PCR confirmed the presence of pH1N1. The virus was subsequently detected on two other premises in Northern Ireland; on one premises, detection followed the pre-export health certification testing of samples from pigs presumed to be subclinically infected as no clinical signs were apparent. None of the premises was linked to another epidemiologically. Sequencing of the haemagglutinin and neuraminidase genes revealed high nucleotide identity (>99.4 per cent) with other pH1N1s isolated from human beings. Genotypic analyses revealed all gene segments to be most closely related to those of contemporary pH1N1 viruses in human beings. It is concluded that all three outbreaks occurred independently, potentially as a result of transmission of the virus from human beings to pigs.


NK1.1+ thymocytes. Adult murine CD4-, CD8- thymocytes contain an NK1.1+, CD3+, CD5hi, CD44hi, TCR-V beta 8+ subset.
CD4-, CD8- thymocytes were purified from thymi obtained from normal C57BL/6 mice. By flow cytometry analysis, 5 to 10% of these double negative (DN) thymocytes were found to express NK1.1 on their surface. The NK1.1+ DN thymocytes were demonstrated, by two-color fluorescence, to be CD3lo, CD5hi, CD44hi, J11d-, B220-, MEL 14-, IL2R- with 60% expressing TCR-V beta 8 as determined by the mAb F23.1. In contrast, splenic and peripheral blood NK cells were NK1.1+, CD3-, CD5-, TCR-V beta 8- with 40 to 60% being MEL 14+. Unlike peripheral NK cells, fresh DN thymocytes enriched for NK1.1+ cells were unable to kill YAC-1, the classical murine NK cell target. However, these cells were able to mediate anti-CD3 redirected lysis even when they were assayed immediately after purification, i.e., with no culture or stimulation. These data demonstrate that adult murine thymocytes contain NK1.1+ cells which are distinct, both by function and phenotype, from peripheral NK cells. These data also raise the issue of a possible NK/T bipotential progenitor cell.


Perceptions of the need for improvements in healthcare after implementation of the Chronic Care Model.
Older people with depression constitute a vulnerable group, and evidence from different parts of the world has demonstrated the need for healthcare improvements at the community level. In this study, we described team members' perceptions of improvements in the care of older people with depression living in the community after the implementation of the Chronic Care Model, with a focus on delivery-system design, self-management support, and teamwork. This follow-up study was based on focus-group interviews with healthcare team members. The data were analyzed by qualitative content analysis. Four themes emerged: (i) ensuring a pathway to the top level of the organization; (ii) the need for leadership from senior managers; (iii) the need to formalize collaboration; and (iv) increasing self-management. Senior managers should cooperate with specialist care givers and administrators in the community. They must also redesign the delivery system to facilitate teamwork and the self-management ability of older people with depression.