Germline selection shapes human mitochondrial DNA diversity.
Approximately 2.4% of the human mitochondrial DNA (mtDNA) genome exhibits common homoplasmic genetic variation. We analyzed 12,975 whole-genome sequences to show that 45.1% of individuals from 1526 mother-offspring pairs harbor a mixed population of mtDNA (heteroplasmy), but the propensity for maternal transmission differs across the mitochondrial genome. Over one generation, we observed selection both for and against variants in specific genomic regions; known variants were more likely to be transmitted than previously unknown variants. However, new heteroplasmies were more likely to match the nuclear genetic ancestry as opposed to the ancestry of the mitochondrial genome on which the mutations occurred, validating our findings in 40,325 individuals. Thus, human mtDNA at the population level is shaped by selective forces within the female germ line under nuclear genetic control, which ensures consistency between the two independent genetic lineages.


Mandibular dimensional changes and skeletal maturity.
Growth and development of the human face provides a fascinating interplay of form and function. Among the various facial bones, the mandible plays a very important role during various growth-modification therapies. These treatment modalities will yield a better result in less time if properly correlated with skeletal maturity. It is very essential to know where the site of growth occurs and also the time when it occurs or ceases to occur. This study was conducted to assess the mandibular dimensions at various stages of skeletal maturation. The subjects included 6 to 18-year-old children who were grouped according to their middle phalanx of the third finger stages of skeletal maturity. Lateral cephalographs were taken and, from their cephalometric tracings, linear and angular measurements of the mandible were made. The values obtained were subjected to statistical analysis. Results showed that the mandibular height, length and symphysis thickness increased with skeletal maturity. An increase in angles SNB (Sella, Nasion, Supramentale) and L1-MP (Long axis lower incisors- Mandibular plane) and a decrease in the gonial angle and ANB (Subspinale, Nasion, Supramentale) angle were observed. The study showed a significant correlation between mandibular growth and skeletal maturity.


Dengue virus inhibits human hematopoietic progenitor growth in vitro.
Dengue disease, whether it be classical dengue fever (DF), dengue hemorrhagic fever (DHF), or dengue shock syndrome (DSS), is frequently associated with hematologic disorders. The underlying cause of these abnormalities is unknown. To determine if an inhibitory effect on human hematopoietic progenitor growth can be observed, normal cord blood mononuclear cells were exposed to low-passaged clinical isolates from DF, DHF, and DSS patients and to the prototype strain of dengue-3 virus (H-87). In primary methylcellulose cultures, there was no inhibition of colony formation. After an initial 8-day liquid culture, inhibition was observed with the isolates, but strain H-87 had no effect. Furthermore, isolates from patients with DSS showed a more potent inhibitory effect. These data represent the first documented study of in vitro impaired progenitor cell growth by dengue virus and suggest that this inhibition could be dependent upon the isolate tested.


Tenosynovitis, peritendinitis and the tennis elbow syndrome.
Both tenosynovitis and peritendinitis of the wrist and forearm and the tennis elbow syndrome are common problems among industrial workers. Yet not much is known of the etiology of these diseases and, especially, of the role of mechanical factors in the etiology. The role of different causative factors is usually studied through comparison of the occurrence rates of the disease in differentially exposed working populations. However, not many such epidemiologic studies have been done. That repetitive movements in manual work may cause tenosynovitis or peritendinitis is generally accepted. Efforts to study further movements and the work positions at fault have, however, failed to show any single set of movements or hand positions. It is often postulated that movements such as repetitive dorsiflexions of the wrist and prosupinations of the forearm are causative for the tennis elbow syndrome, but there is no scientific proof for this argumentation. There are also several proposed mechanisms for the pathogenesis of the disease. In the treatment of the acute phase of these diseases in an occupational health setting, rest for the affected limb is essential. Prevention of the diseases and their recurrences probably requires changes in work conditions. Yet, at the moment, there is not much scientific basis for these measures.


Role of defective calcium regulation in cardiorespiratory dysfunction in Huntington's disease.
Huntington's disease (HD) is a progressive, autosomal dominant neurodegenerative disorder affecting striatal neurons beginning in young adults with loss of muscle coordination and cognitive decline. Less appreciated is the fact that patients with HD also exhibit cardiac and respiratory dysfunction, including pulmonary insufficiency and cardiac arrhythmias. The underlying mechanism for these symptoms is poorly understood. In the present study we provide insight into the cause of cardiorespiratory dysfunction in HD and identify a potentially novel therapeutic target. We now show that intracellular calcium (Ca2+) leak via posttranslationally modified ryanodine receptor/intracellular calcium release (RyR) channels plays an important role in HD pathology. RyR channels were oxidized, PKA phosphorylated, and leaky in brain, heart, and diaphragm both in patients with HD and in a murine model of HD (Q175). HD mice (Q175) with endoplasmic reticulum Ca2+ leak exhibited cognitive dysfunction, decreased parasympathetic tone associated with cardiac arrhythmias, and reduced diaphragmatic contractile function resulting in impaired respiratory function. Defects in cognitive, motor, and respiratory functions were ameliorated by treatment with a novel Rycal small-molecule drug (S107) that fixes leaky RyR. Thus, leaky RyRs likely play a role in neuronal, cardiac, and diaphragmatic pathophysiology in HD, and RyRs are a potential novel therapeutic target.


Lateral hypothalamic NMDA receptors and glutamate as physiological mediators of eating and weight control.
To determine whether endogenous lateral hypothalamic (LH) glutamate and its N-methyl-D-aspartate (NMDA) receptors might participate in the stimulation of natural eating, LH injection of the NMDA antagonist D-(-)-2-amino-5-phosphonopentanoic acid (D-AP5) was tested in adult male rats for suppressive actions on feeding elicited by 1) NMDA, kainic acid or D, L-alpha-amino-3-hydroxy-5-methylisoxazole (AMPA) injected into the LH; 2) food deprivation; and 3) the onset of the nocturnal period. D-AP5 (10-100 nmol) reduced by 72-90% the approximately 10-g eating response elicited by NMDA (10 nmol) without affecting the quantitatively similar eating responses elicited by kainic acid (1.0 nmol) or AMPA (1.0 nmol). This treatment also suppressed deprivation-induced eating by as much as 61% and nocturnal eating by as much as 40%. To determine its long-term effects, D-AP5 (50 nmol) was injected bilaterally into the LH twice a day for 8 consecutive days. This treatment caused up to 65% reductions in daily food intake and body weight loss of up to 13 g/day. These findings, showing behaviorally selective suppressions of eating and body weight by D-AP5, argue that endogenous LH glutamate acts to regulate natural eating and body weight and that NMDA receptors participate in these functions.


Second monovalent SARS-CoV-2 mRNA booster restores Omicron-specific neutralizing activity in both nursing home residents and health care workers.
We examined whether the second monovalent SARS-CoV-2 mRNA booster increased antibody levels and their neutralizing activity to Omicron variants in nursing home residents (NH) residents and healthcare workers (HCW). We sampled 376 NH residents and 63 HCW after primary mRNA vaccination, first and second boosters, for antibody response and pseudovirus neutralization assay against SARS-CoV-2 wild-type (WT) (Wuhan-Hu-1) strain, Omicron BA.1 and BA.5 variants. Antibody levels and neutralizing activity progressively increased with each booster but subsequently waned over 3-6 months. NH residents, both those without and with prior infection, had a robust geometric mean fold rise (GMFR) of 8.1 (95% CI 4.4, 14.8) and 7.8 (95% CI 4.8, 12.9) respectively in Omicron-BA.1 subvariant specific neutralizing antibody levels following the second booster vaccination (p < 0.001). These results support the ongoing efforts to ensure that both NH residents and HCW are up-to-date on recommended SARS-CoV-2 vaccine booster doses.


Concurrent Verbal Encouragement and Wingate Anaerobic Cycle Test Performance in Females: Athletes vs. Non-Athletes.
To examine the effect of concurrent verbal encouragement on the performance of the WAnT in female athletes vs. female non-athletes. College-age female subjects were recruited where ten of the subjects were intercollegiate athletes (ATH, n1 =10) and the nine were non-athletes (NON, n2 =9). The WAnT was novel to all subjects and the subjects were blinded to the study's purpose. Prior to the experimental trials, subjects were measured for body composition and performed a familiarity WAnT trial without verbal encouragement. Subjects then performed the WAnT twice, once with concurrent verbal encouragement (VE) and once without (NVE), in a balanced cross-over design. Peak (PP) and mean power (MP), and total work (TW) were compared between ATH and NON across VE and NVE using an ANOVA (1 between, 1 within), α=0.05. ATH and NON did not differ (p>0.05) in age or body composition with the exception of fat-free mass which differed significantly (ATH=53.7±6.6, NON=46.1±5.7 kg) (p<0.05). A significant (p<0.05) main effect for ATH/NON was observed where ATH outperformed NON when pooled across VE/NVE trials for PP (ATH=13.0±1.4, NON=11.3±1.7 W·kg-1), MP (ATH=7.7±1.1, NON=6.7±0.9 W·kg-1) and TW (ATH=232±35, NON=201±26 J·kg-1). When pooled across all subjects (ATH and NON), the VE/NVE trials did not differ (p>0.05) for PP (VE=12.4±1.7, NVE=12.0±1.9 W·kg-1), MP (VE=7.3±1.1, NVE=7.2±1.2 W·kg-1) and TW (VE=219±33, NVE=215±35 J·kg-1). The ATH/NON interaction with VE/NVE was not significant (p>0.05). Concurrent verbal encouragement does not affect performance on the WAnT in females, nor does it affect WAnT performance in female athletes and non-athletes differently.


Nanostructured potential of optical trapping using a plasmonic nanoblock pair.
We performed two-dimensional mapping of optical trapping potentials experienced by a 100 nm dielectric particle above a plasmon-resonant gold nanoblock pair with a gap of several nanometers. Our results demonstrate that the potentials have nanoscale spatial structures that reflect the near-field landscape of the nanoblock pair. When an incident polarization parallel to the pair axis is rotated by 90°, a single potential well turns into multiple potential wells separated by a distance smaller than the diffraction limit; this is associated with super-resolution optical trapping. In addition, we show that the trap stiffness can be enhanced by approximately 3 orders of magnitude compared to that with conventional far-field trapping.


Clinical significance not statistical significance: a simple Bayesian alternative to p values.
To take the common "Bayesian" interpretation of conventional confidence intervals to its logical conclusion, and hence to derive a simple, intuitive way to interpret the results of public health and clinical studies. The theoretical basis and practicalities of the approach advocated is at first explained and then its use is illustrated by referring to the interpretation of a real historical cohort study. The study considered compared survival on haemodialysis (HD) with that on continuous ambulatory peritoneal dialysis (CAPD) in 389 patients dialysed for end stage renal disease in Leicestershire between 1974 and 1985. Careful interpretation of the study was essential. This was because although it had relatively low statistical power, it represented all of the data that were available at the time and it had to inform a critical clinical policy decision: whether or not to continue putting the majority of new patients onto CAPD. Conventional confidence intervals are often interpreted using subjective probability. For example, 95% confidence intervals are commonly understood to represent a range of values within which one may be 95% certain that the true value of whatever one is estimating really lies. Such an interpretation is fundamentally incorrect within the framework of conventional, frequency-based, statistics. However, it is valid as a statement of Bayesian posterior probability, provided that the prior distribution that represents pre-existing beliefs is uniform, which means flat, on the scale of the main outcome variable. This means that there is a limited equivalence between conventional and Bayesian statistics, which can be used to draw simple Bayesian style statistical inferences from a standard analysis. The advantage of such an approach is that it permits intuitive inferential statements to be made that cannot be made within a conventional framework and this can help to ensure that logical decisions are taken on the basis of study results. In the particular practical example described, this approach is applied in the context of an analysis based upon proportional hazards (Cox) regression. The approach proposed expresses conclusions in a manner that is believed to be a helpful adjunct to more conventional inferential statements. It is of greatest value in those situations in which statistical significance may bear little relation to clinical significance and a conventional analysis using p values is liable to be misleading. Perhaps most importantly, this includes circumstances in which an important public health or clinical decision must be based upon a study that has unavoidably low statistical power. However, it is also useful in situations in which a decision must be based upon a large study that indicates that an effect that is highly statistically significant seems too small to be of practical relevance. In the illustrative example described, the approach helped in making a decision regarding the use of CAPD in Leicestershire during the latter half of the 1980s.


Functional specialization in regulation and quality control in thermal adaptive evolution.
Distinctive survival strategies, specialized in regulation and in quality control, were observed in thermal adaptive evolution with a laboratory Escherichia coli strain. The two specialists carried a single mutation either within rpoH or upstream of groESL, which led to the activated global regulation by sigma factor 32 or an increased amount of GroEL/ES chaperonins, respectively. Although both specialists succeeded in thermal adaptation, the common winner of the evolution was the specialist in quality control, that is, the strategy of chaperonin-mediated protein folding. To understand this evolutionary consequence, multilevel analyses of cellular status, for example, transcriptome, protein and growth fitness, were carried out. The specialist in quality control showed less change in transcriptional reorganization responding to temperature increase, which was consistent with the finding of that the two specialists showed the biased expression of molecular chaperones. Such repressed changes in gene expression seemed to be advantageous for long-term sustainability because a specific increase in chaperonins not only facilitated the folding of essential gene products but also saved cost in gene expression compared with the overall transcriptional increase induced by rpoH regulation. Functional specialization offered two strategies for successful thermal adaptation, whereas the evolutionary advantageous was more at the points of cost-saving in gene expression and the essentiality in protein folding.


Self-detection of atrial fibrillation in an aged population: three-year follow-up of the LietoAF intervention study.
Atrial fibrillation (AF) is often asymptomatic and undiagnosed until an ischaemic stroke occurs. An irregular pulse is a key manifestation of AF. We assessed whether pulse self-palpation is feasible in screening of AF. Altogether 205 residents of Lieto municipality aged ≥75 years were randomized in 2012 to receive brief education on pulse palpation focusing on evaluating rhythm regularity. Self-detected pulse irregularity and new AF diagnoses were recorded, and the subjects' quality of life and use of health care services were assessed during a three-year follow-up. The subjects' median age was 78.2 [3.8] years, and 89 (43.4%) were men. Overall, 139 (68%) subjects had initial good motivation/capability for regular palpation. At four months, 112 (80.6%) subjects with good and 26 (39.4%) with inadequate motivation/capability palpated their pulse daily. At 12 months, 120 (58.5%) and at 36 months, 69 (33.7%) subjects palpated their pulse at least weekly. During the intervention, 67 (32.7%) subjects reported pulse irregularity. New AF was found in 10 (4.9%) subjects, 7 (70%) of whom had reported pulse irregularity. Pulse irregularity independently predicted new AF, but only one (0.5%) subject with new AF sought undelayed medical attention due to pulse irregularity. Quality of life and number of outpatient clinic visits remained unchanged during follow-up. Pulse palpation can be learned also by the elderly, but it is challenging to form a continuing habit. The low persistence of pulse self-palpation limits its value in the screening of AF, and strategies to promote persistence and research on alternative screening methods are needed. http://www.ClinicalTrials.gov identifier: NCT01721005. The trial was registered retrospectively on October 26, 2012.


Deep-Red-Emitting Colloidal Quantum Well Light-Emitting Diodes Enabled through a Complex Design of Core/Crown/Double Shell Heterostructure.
Extending the emission peak wavelength of quasi-2D colloidal quantum wells has been an important quest to fully exploit the potential of these materials, which has not been possible due to the complications arising from the partial dissolution and recrystallization during growth to date. Here, the synthetic pathway of (CdSe/CdS)@(1-4 CdS/CdZnS) (core/crown)@(colloidal atomic layer deposition shell/hot injection shell) hetero-nanoplatelets (NPLs) using multiple techniques, which together enable highly efficient emission beyond 700 nm in the deep-red region, is proposed and demonstrated. Given the challenges of using conventional hot injection procedure, a method that allows to obtain sufficiently thick and passivated NPLs as the seeds is developed. Consequently, through the final hot injection shell coating, thick NPLs with superior optical properties including a high photoluminescence quantum yield of 88% are achieved. These NPLs emitting at 701 nm exhibit a full-width-at-half-maximum of 26 nm, enabled by the successfully maintained quasi-2D shape and minimum defects of the resulting heterostructure. The deep-red light-emitting diode (LED) device fabricated with these NPLs has shown to yield a high external quantum efficiency of 6.8% at 701 nm, which is on par with other types of LEDs in this spectral range.


In vitro comparison of the cytotoxic effects of statins on U266 myeloma cell line.
Statins are one of the most widely used drugs and have antilipidemic effects as well as antioxidant, anti-inflammatory, anti-angiogenic and anti-tumorigenic effects. It has been shown that the synergistic combinations of statins which can provide better clinical benefit in the treatment of cancer and if administered with other anticancer agents, may be an alternative treatment modality. The aim of this study was to assess the efficacy of administrating statin in multiple myeloma (MM) cell line on cell proliferation. U266 myeloma cells were cultured in 25 or 75 cm[2] flasks by using cell culture medium mixtures obtained with the supplementation of 10 per cent foetal bovine serum and one per cent of penicillin-streptomycin into RPMI 1640 medium. When the cells reached confluence (reached to the density of 70%), they were reproduced by passaging. Cytotoxicity was evaluated by using the XTT test. Statins (atorvastatin and simvastatin), were administered to the U266 myeloma cell line at 100, 50, 25, 12.5, 6.25 and 3.12 μM concentrations. Inhibitor concentration 50 (IC50) values calculated for atorvastatin and simvastatin were determined as 94 and 38 μM, respectively. While 100, 50, 25, 12.5, 6.25 and 3.12 μM concentrations were used for bortezomib, the IC50value calculated for this agent was 18.2 nM. When six concentrations of bortezomib used in the study were combined with 12.5 μM inactive concentrations of statins that did not cause inhibition in cell proliferation, both atorvastatin and simvastatin increased the effect of bortezomib at all the concentrations used, and simvastatin showed a stronger efficacy than atorvastatin. Our in vitro results indicated that atorvastatin and simvastatin when used along with the conventional treatment in myeloma patients, may improve the effectiveness of the standard therapy and prevent the bortezomib-induced cytotoxic and neurotoxic side effects when used at a low dose. Further studies need to be done in MM patints to confirm these findings.


Performance prediction of F1 hybrids between recombinant inbred lines derived from two elite maize inbred lines.
Selection of recombinant inbred lines (RILs) from elite hybrids is a key method in maize breeding especially in developing countries. The RILs are normally derived by repeated self-pollination and selection. In this study, we first investigated the accuracy of different models in predicting the performance of F(1) hybrids between RILs derived from two elite maize inbred lines Zong3 and 87-1, and then compared these models through simulation using a wider range of genetic models. Results indicated that appropriate prediction models depended on genetic architecture, e.g., combined model using breeding value and genome-wide prediction (BV+GWP) has the highest prediction accuracy for high V(D)/V(A) ratio (>0.5) traits. Theoretical studies demonstrated that different components of genetic variance were captured by different prediction models, which in turn explained the accuracy of these models in predicting the F(1) hybrid performance. Based on genome-wide prediction model (GWP), 114 untested F(1) hybrids possibly having higher grain yield than the original F(1) hybrid Yuyu22 (the single cross between Zong3 and 87-1) have been identified and recommended for further field test.


Giving-updensity and dietary shifts in the white-footed mouse, Peromyscus leucopus.
Dietary shifts are commonly exhibited by omnivorous consumers when foraging from variable food resources. One advantage of dietary shifts for a consumer is the ability to gain complementary resources from different foods. In addition, dietary shifts often affect food-web dynamics. Despite the importance of dietary shifts to organismal, community, and ecosystem ecology, empirical studies of the ecological mechanisms that control dietary shifts are limited in scope. In this study, we tested the effects of complementary resources on dietary shifts of an omnivorous mammal, the white-footed mouse Peromyscus leucopus, in the context of depletable food patches in the natural environment. We used two complementary resources: seeds that provide a higher energy gain per unit handling time and mealworms that provide a higher protein gain per unit handling time. Stable isotopes of carbon and nitrogen (delta13C, delta15N) in mouse plasma were used to quantify dietary shifts, and we determined giving-up density (GUD), the food density at which a forager leaves a food patch (for an optimal forager, it should correspond to the quitting harvest rate that balances net fitness gain with various costs of foraging). The results showed that GUD increased most significantly when a mixture of seeds and mealworms was added, compared to when only seeds or mealworms were added. This suggests that, given a similar level of food availability, a patch with a mixture of complementary foods is of higher quality than a patch with only one type of food. Moreover, GUD measured with seeds (GUDs) correlated positively with seed availability, and GUD measured with mealworms (GUDmw) correlated positively with mealworm availability, indicating that the marginal value of seeds or mealworms decreases with their relatively availability in the environment. As GUDs increased, P. leucopus shifted their diets toward higher trophic levels, and as GUDmw increased, P. leucopus shifted their diets toward lower trophic levels, suggesting dietary shifts driven by food complementarity. This study demonstrated that the combination of giving-up density and stable-isotope analysis holds great potential for testing ecological mechanisms underlying dietary shifts.


Behavioral Disturbances: An Innovative Approach to Monitor the Modulatory Effects of a Nutraceutical Diet.
In dogs, diets are often used to modulate behavioral disturbances related to chronic anxiety and stress caused by intense and restless activity. However, the traditional ways to monitor behavioral changes in dogs are complicated and not efficient. In the current clinical evaluation, a new, simple monitoring system was used to assess the effectiveness of a specific diet in positively modulating the intense and restless activity of 24 dogs of different ages and breeds. This protocol describes how to easily and rapidly evaluate improvement in a set of symptoms related to generalized anxiety by using a specific sensor, a mobile phone app, a wireless router, and a computer. The results showed that dogs treated with specific diets showed significant improvement in the times spent active and at rest after 10 days (p < 0.01 and p < 0.05, respectively). These dogs also showed an overall significant improvement in clinical and behavioral symptoms. A specific sensor, along with its related hardware, was demonstrated to successfully monitor behavioral changes relating to movement in dogs.


Quantitative real-time RT-PCR detection of breast cancer micrometastasis using a multigene marker panel.
Real-time RT-PCR is a relatively new technology that uses an online fluorescence detection system to determine gene expression levels. It has the potential to significantly improve detection of breast cancer metastasis by virtue of its exquisite sensitivity, high throughput capacity and quantitative readout system. To assess the utility of this technology in breast cancer staging, we determined the relative expression levels of 12 cancer-associated genes (mam, PIP, mamB, CEA, CK19, VEGF, erbB2, muc1, c-myc, p97, vim and Ki67) in 51 negative-control normal lymph nodes and in 17 histopathology-positive ALNs. We then performed a receiver operating characteristic (ROC) curve analysis to determine the sensitivity and specificity levels of each gene. Areas under the ROC curve indicated that the most accurate diagnostic markers were mam (99.6%), PIP (93.3%), CK19 (91.0%), mamB (87.9%), muc1 (81.5%) and CEA (79.4.0%). mam was overexpressed in 16 of 17 lymph nodes known to contain metastatic breast cancer at levels ranging from 22- to 2.8 x 10(5)-fold above normal mean expression, whereas PIP was overexpressed from 30- to 2.2 x 10(6)-fold above normal in 13 lymph nodes. Real-time RT-PCR analysis of pathology-negative LN from breast cancer patients revealed evidence of overexpression of PIP (6 nodes), mam (3 nodes) and CEA (1 node) in 8 of 21 nodes (38%). Our results provide evidence that mam, PIP, CK19, mamB, muc1 and CEA can be applied as a panel for detection of metastatic and occult micrometastatic disease.


A comparative study of complementary and alternative medicine use among heterosexually and lesbian identified women: data from the ESTHER Project (Pittsburgh, PA, 2003-2006).
The prevalence of complementary and alternative medicine (CAM) use among women in the United States is high. Little is known about how CAM use may differ based on sexual orientation. Study aims were to measure the prevalence of CAM use in a community sample of women, explore differences in CAM use patterns by sexual orientation, and identify correlates of CAM use. Analyses were based on women (Total N = 879; n = 479 lesbians) enrolled in the Epidemiologic STudy of HEalth Risk in Women (ESTHER) Project, a cross-sectional heart-disease risk-factor study. Data were collected through convenience sampling of adult females in Pittsburgh, PA (2003-2006). Main outcome measures included lifetime and past 12-month CAM use, and types of CAM modalities used in the past 12 months. The prevalence of having ever used CAM was 49.8%, with 42% having reported CAM use within the past 12 months. Lesbians had greater odds of having ever used CAM (adjusted odds ratio [AOR] = 1.68 [95% confidence interval (CI): 1.23, 2.28]) and of having used CAM in the past 12 months (AOR = 1.44 [CI: 1.06, 1.97]) than heterosexuals. In multivariate analyses, correlates of lifetime and past 12-month CAM use included being lesbian, white, higher educated, and a large-city resident; experiencing perceived discrimination in a health care setting; and having a greater spirituality rating and a history of a diagnosed mental health disorder. Past 12-month CAM use was also associated with having a provider of usual health care. Among women who used CAM within the past 12 months, heterosexuals had significantly higher yoga participation rates than lesbians. Sexual orientation is important in understanding lifetime and past 12-month CAM use. Because of the high prevalence of CAM use found in this study, medical practitioners should inquire about the CAM practices of female patients, particularly lesbians.


Dating apps and websites as tools to reach anonymous sexual contacts during an outbreak of hepatitis A among men who have sex with men, Berlin, 2017.
BackgroundIn an outbreak of hepatitis A among men who have sex with men (MSM) in Berlin (2016 and 2017), patients frequently reported anonymous sex and use of dating applications to meet sexual contacts, hampering tracing and vaccination of contacts.AimOur objective was to evaluate dating apps and websites as a means of spreading prevention messages among MSM during the ongoing outbreak.MethodsAdvertisements in different formats were placed on three MSM dating apps and eight websites for anonymous dating during three weeks in March and April 2017. We calculated frequency of ads shown and click-through rates (CTR) and investigated the independent effect of format and platform on the number of clicks using a negative binomial regression model. We evaluated the campaign's impact using a survey among visitors of a large gay-lesbian street-festival in Berlin.ResultsOverall, 1,920,180 ads were shown and clicked on 8,831 times (CTR = 0.46%). The multivariable model showed significantly more clicks on one dating app (incidence rate ratio (IRR) = 9.5; 95% confidence interval (CI): 7.7-12.2) than on websites and on full-screen ads (IRR = 3.1; 95% CI: 2.5-3.8) than on banner ads. Of 266 MSM who participated in the survey, 190 (71%) knew about the outbreak and 39 (15%) declared to have been vaccinated recently because of the campaign.ConclusionsDating apps provided a means to rapidly reach and influence a substantial number of MSM in Berlin and should complement case-based contact tracing among MSM in outbreak settings. Clicking on ads depended on platform and format used.


Long Working Hours and the Prevalence of Masked and Sustained Hypertension.
Previous studies on the effect of long working hours on blood pressure have shown inconsistent results. Mixed findings could be attributable to limitations related to blood pressure measurement and the lack of consideration of masked hypertension. The objective was to determine whether individuals who work long hours have a higher prevalence of masked and sustained hypertension. Data were collected at 3-time points over 5 years from 3547 white-collar workers. Long working hours were self-reported, and blood pressure was measured using Spacelabs 90207. Workplace clinic blood pressure was defined as the mean of the first 3readings taken at rest at the workplace. Ambulatory blood pressure was defined as the mean of the next readings recorded every 15 minutes during daytime working hours. Masked hypertension was defined as clinic blood pressure < 140/90 mm Hg and ambulatory blood pressure ≥135/85 mm Hg. Sustained hypertension was defined as clinic blood pressure ≥140/90 mm Hg and ambulatory blood pressure ≥135/85 mm Hg or being treated hypertension. Long working hours were associated with the prevalence of masked hypertension (prevalence ratio 49+=1.70 [95% CI, 1.09-2.64]), after adjustment for sociodemographics, lifestyle-related risk factors, diabetes mellitus, family history of cardiovascular disease, and job strain. The association with sustained hypertension was of a comparable magnitude (prevalence ratio 49+=1.66 [95% CI, 1.15-2.50]). Results suggest that long working hours are an independent risk factor for masked and sustained hypertension. Workplace strategies targeting long working hours could be effective in reducing the clinical and public health burden of hypertension.


Holographic grating formation in dye- and fullerene C(60)-doped nematic liquid-crystal film.
Transient and persistent holographic gratings have been observed in dye- and fullerene C(60)-doped nematic liquid-crystal films. The nature and time evolution of the underlying mechanisms, such as space-charge field production, flows, and dielectric- and conductivity-induced torques, and the resultant director axis reorientation and refractive-index gratings are examined.


Novel strategy to treat a case of recurrent lymphocytic hypophysitis using rituximab.
Lymphocytic hypophysitis is an uncommon autoimmune condition that often results in significant morbidity. Although most cases resolve spontaneously or after a short course of steroids, rarely, refractory cases can cause persistent neurological deficits despite aggressive medical and surgical management. A 41-year-old woman presented with progressive visual loss in the left eye and was found to have a sellar mass. She underwent transsphenoidal surgery because of lesion enlargement. Histopathology was consistent with adenohypophysitis with B-cell predominance. Despite steroid treatment, her neurological condition worsened and she experienced loss of vision in the right eye. Craniotomy with decompression of the right optic nerve was performed. Her condition improved initially, but she continued to have progressive visual compromise over the following months. She was therefore treated with rituximab, a monoclonal antibody against B cells. Her vision improved significantly within a few weeks. There was no clinical or radiographic exacerbation 2 years after starting immunotherapy. Rituximab, an anti-CD20 antibody that specifically depletes B lymphocytes, can be an effective treatment strategy for patients with steroid-refractory, B cell-predominant lymphocytic hypophysitis.


Nurse-Led Supportive Care Intervention for Men With Advanced Prostate Cancer.
To understand the context for implementing ProsCare by prostate cancer specialist nurses (PCSNs) and, in doing so, further develop the intervention and implementation strategy. 30 PCSNs participated in four semistructured focus groups to evaluate a telephone-based supportive care intervention led by nurses for men with advanced prostate cancer. Data were coded into the Consolidated Framework for Implementation Research to evaluate the ProsCare program content and guide the implementation and evaluation of this targeted program for men with advanced prostate cancer. Participants strongly endorsed specific ProsCare program components amid a recommendation of delivery mechanisms and a comprehensive centralized implementation strategy, including PCSN role promotion, education, and professional development. PCSNs validated ProsCare and supported its implementation as a supportive care intervention. ProsCare is a feasible nurse-led intervention closely matched with men's supportive care needs and the PCSN scope of practice.


Wharton's jelly-derived mesenchymal stem cells combined with praziquantel as a potential therapy for Schistosoma mansoni-induced liver fibrosis.
Liver fibrosis is one of the most serious consequences of S. mansoni infection. The aim of the present study was to investigate the potential anti-fibrotic effect of human Wharton's jelly-derived mesenchymal stem cells (WJMSCs) combined with praziquantel (PZQ) in S. mansoni-infected mice. S. mansoni-infected mice received early (8(th) week post infection) and late (16(th) week post infection) treatment with WJMSCs, alone and combined with oral PZQ. At the 10(th) month post infection, livers were collected for subsequent flow cytometric, histopathological, morphometric, immunohistochemical, gene expression, and gelatin zymographic studies. After transplantation, WJMSCs differentiated into functioning liver-like cells as evidenced by their ability to express human hepatocyte-specific markers. Regression of S. mansoni-induced liver fibrosis was also observed in transplanted groups, as evidenced by histopathological, morphometric, and gelatin zymographic results besides decreased expression of three essential contributors to liver fibrosis in this particular model; alpha smooth muscle actin, collagen-I, and interleukin-13. PZQ additionally enhanced the beneficial effects observed in WJMSCs-treated groups. Our results suggest that combining WJMSCs to PZQ caused better enhancement in S. mansoni-induced liver fibrosis, compared to using each alone.


Threats: power, family mealtimes, and social influence.
One of the most basic topics in social psychology is the way one agent influences the behaviour of another. This paper will focus on threats, which are an intensified form of attempted behavioural influence. Despite the centrality to the project of social psychology, little attention has been paid to threats. This paper will start to rectify this oversight. It reviews early examples of the way social psychology handles threats and highlights key limitations and presuppositions about the nature and role of threats. By contrast, we subject them to a programme of empirical research. Data comprise video records of a collection of family mealtimes that include preschool children. Threats are recurrent in this material. A preliminary conceptualization of features of candidate threats from this corpus will be used as an analytic start point. A series of examples are used to explicate basic features and dimensions that build the action of threatening. The basic structure of the threats uses a conditional logic: if the recipient continues problem action/does not initiate required action then negative consequences will be produced by the speaker. Further analysis clarifies how threats differ from warnings and admonishments. Sequential analysis suggests threats set up basic response options of compliance or defiance. However, recipients of threats can evade these options by, for example, reworking the unpleasant upshot specified in the threat, or producing barely minimal compliance. The implications for broader social psychological concerns are explored in a discussion of power, resistance, and asymmetry; the paper ends by reconsidering the way social influence can be studied in social psychology.


Adenomyosis demonstrates increased expression of the basic fibroblast growth factor receptor/ligand system compared with autologous endometrium.
Basic fibroblast growth factor (bFGF) is an angiogenic growth factor present in human endometrium and myometrium. Women with leiomyoma-related abnormal uterine bleeding have local dysregulation of bFGF and its type 1 receptor (FGF-R). This study was designed to evaluate if adenomyosis expresses bFGF and FGF-R, and if present, to compare bFGF and FGF-R expression in adenomyosis and autologous endometrium. Menopausal uteri containing endometrium and adenomyosis were analyzed using immunohistochemistry with monoclonal antibodies specific for bFGF, FGF-R, and proliferating cell nuclear antigen (PCNA), a marker of cellular proliferation. The expression and intensity of staining for bFGF, FGF-R, and PCNA were evaluated in the glandular epithelium and stroma of adenomyosis and endometrium. Glandular epithelial staining was significantly greater in adenomyosis compared with autologous endometrium for bFGF and FGF-R. Stromal staining for bFGF and PCNA was significantly increased in adenomyosis compared with autologous endometrium. Upregulation of the bFGF receptor/ligand system and increased cellular proliferation in adenomyosis may contribute to the pathogenesis of abnormal uterine bleeding associated with adenomyosis.


Raman imaging highlights biochemical heterogeneity of human eosinophils versus human eosinophilic leukaemia cell line.
Eosinophils are acidophilic granulocytes that develop in the bone marrow. Although their population contributes only to approximately 1-6% of all leucocytes present in the human blood, they possess a wide range of specific functions. They play a key role in inflammation-regulating processes, when their numbers can increased to above 5 × 109 /l of peripheral blood. Their characteristic feature is the presence of granules containing eosinophil peroxidase (EPO), the release of which can trigger a cascade of events promoting oxidative stress, apoptosis or necrosis, leading finally to cell death. Raman spectroscopy is a powerful technique to detect EPO, which comprises a chromophore protoporphyrin IX. Another cell structure associated with inflammation processes are lipid bodies (lipid-rich organelles), also well recognized and imaged using high resolution confocal Raman spectroscopy. In this work, eosinophils isolated from the blood of a human donor were analysed versus their model, EoL-1 human eosinophilic leukaemia cell line, by Raman spectroscopic imaging. We showed that EPO was present only in primary cells and not found in the cell line. Eosinophils were activated using phorbol 12-myristate 13-acetate, which resulted in lipid bodies formation. An effect of cells stimulation was studied and compared for eosinophils and EoL-1.


Alterations in biochemical composition and ribonucleic acid metabolism induced in rat liver by cortisone.
An investigation of the effect of cortisone administration upon the chemical composition of intracellular particulates of rat liver has been made. Livers were homogenized in 0.25 M sucrose solutions and submitted to differential centrifugation. Five fractions were prepared: mitochondria (Mit), microsomes (Mi), ultracentrifugable (U), non-sedimentable (S), and nuclear (Nuc). Measurement was made of total and polymerized RNA, nitrogen, lipide P, and uptake of P(32) by the RNA of each fraction. The following observations were made:- Cortisone administration caused a fall in concentration in all measured constituents except glycogen. On a per liver basis, however, total liver RNA was unchanged in amount; nitrogen content of Mi fell and that of S increased; the lipide P of Mit and Mi also decreased. The biochemical composition of a statistical mitochondrion was significantly altered; in contrast, the microsomal fraction decreased in amount, but the relationship between the chemical constituents was unchanged. When polymerized RNA was sought by a process involving precipitation from ethanol at 20 degrees C., none was found in the Mit of cortisone livers and the amount in Mi was much less than found in the normal. When, however, precipitation was conducted at 4 degrees C., yields of polymerized RNA in all fractions after cortisone were equal to or greater than those found in the normal. Furthermore, incubation of mixtures of homogenates from normal and cortisone livers resulted in loss of warm precipitable RNA. These data strongly suggest the presence of an enzyme in cortisone livers which upon incubation with normal livers made preparation of polymerized RNA virtually impossible by use of the warm method. This agent, thought to operate in vivo and in vitro, was not present in significant amounts in normal livers, since incubation in this instance had no effect upon the amount of polymerized RNA. Mit from cortisone livers obtained by the cold technique had a significantly decreased rate of incorporation of P(32) even though the yield of RNA from this fraction was increased. To reconcile these observations, it was proposed that under the influence of cortisone a variant of normal RNA is synthesized or normal RNA is converted to this variant. This "new" RNA has new solubility properties, a new rate of incorporation of P(32), and conceivably it cannot act as a template for normal protein synthesis.


Regulatory role of tryptophan degradation pathway in HLA-G expression by human monocyte-derived dendritic cells.
Dendritic cells (DC) are strong inducers of immunity but they can also be tolerogenic. During monocyte differentiation to DC the immunosuppressive indoleamine-2,3-dioxygenase (IDO) is induced. IDO degrades Trp to kynurenine, which is further metabolized to 3-hydroxyanthranilic acid. DC can also express mRNA and protein of the tolerogenic molecule HLA-G, but there is no surface expression. We studied the effect of the Trp degrading pathway on HLA-G expression by DC. When monocytes were differentiated to immature DC in presence of either Trp or its metabolites kynurenine or 3-hydroxyanthranilic acid they expressed cell surface HLA-G, and Trp also increased shedding of HLA-G1. Trp induced HLA-G cell surface expression when present during maturation with IFN-gamma+LPS, but not with TNF-alpha. Kynurenine increased HLA-G expression in both TNF-alpha and IFN-gamma+LPS matured DC, and 3-hydroxyanthranilic acid had a very weak effect on HLA-G cell surface expression when present during maturation. Shedding of HLA-G1 was more pronounced in IFN-gamma+LPS-matured DC than in immatured DC. Maturation with IFN-gamma+LPS in presence of kynurenine also increased HLA-G5 secretion. The mechanism involved seems to be post-translational as mRNA and cellular HLA-G protein content was not increased with Trp, kynurenine or 3-hydroxyanthranilic acid treatments. Finally, immature DC preincubated with Trp, kynurenine and 3-hydroxyanthranilic acid have after a decreased capacity to stimulate T cells in mixed lymphocyte reaction. In IFN-gamma+LPS-matured DC this decreased capacity was obtained with kynurenine and 3-hydroxyanthranilic acid. These results suggest that IDO can induce HLA-G cell surface expression in DC, and that these two molecules can cooperate in the immune suppression.


PlanTAPDB, a phylogeny-based resource of plant transcription-associated proteins.
Diversification of transcription-associated protein (TAP) families during land plant evolution is a key process yielding increased complexity of plant life. Understanding the evolutionary relationships between these genes is crucial to gain insight into plant evolution. We have determined a substantial set of TAPs that are focused on, but not limited to, land plants using PSI-BLAST searches and subsequent filtering and clustering steps. Phylogenies were created in an automated way using a combination of distance and maximum likelihood methods. Comparison of the data to previously published work confirmed their accuracy and usefulness for the majority of gene families. Evidence is presented that the flowering plant apical stem cell regulator WUSCHEL evolved from an ancestral homeobox gene that was already present after the water-to-land transition. The presence of distinct expanded gene families, such as COP1 and HIT in moss, is discussed within the evolutionary backdrop. Comparative analyses revealed that almost all angiosperm transcription factor families were already present in the earliest land plants, whereas many are missing among unicellular algae. A global analysis not only of transcription factors but also of transcriptional regulators and novel putative families is presented. A wealth of data about plant TAP families and all data accrued throughout their automated detection and analysis are made available via the PlanTAPDB Web interface. Evolutionary relationships of these genes are readily accessible to the nonexpert at a mouse-click. Initial analyses of selected gene families revealed that PlanTAPDB can easily be exerted for knowledge discovery.


Genomic structure and expression of Jmjd6 and evolutionary analysis in the context of related JmjC domain containing proteins.
The jumonji C (JmjC) domain containing gene 6 (Jmjd6, previously known as phosphatidylserine receptor) has misleadingly been annotated to encode a transmembrane receptor for the engulfment of apoptotic cells. Given the importance of JmjC domain containing proteins in controlling a wide range of diverse biological functions, we undertook a comparative genomic analysis to gain further insights in Jmjd6 gene organisation, evolution, and protein function. We describe here a semiautomated computational pipeline to identify and annotate JmjC domain containing proteins. Using a sequence segment N-terminal of the Jmjd6 JmjC domain as query for a reciprocal BLAST search, we identified homologous sequences in 62 species across all major phyla. Retrieved Jmjd6 sequences were used to phylogenetically analyse corresponding loci and their genomic neighbourhood. This analysis let to the identification and characterisation of a bi-directional transcriptional unit compromising the Jmjd6 and 1110005A03Rik genes and to the recognition of a new, before overseen Jmjd6 exon in mammals. Using expression studies, two novel Jmjd6 splice variants were identified and validated in vivo. Analysis of the Jmjd6 neighbouring gene 1110005A03Rik revealed an incident deletion of this gene in two out of three earlier reported Jmjd6 knockout mice, which might affect previously described conflicting phenotypes. To determine potentially important residues for Jmjd6 function a structural model of the Jmjd6 protein was calculated based on sequence conservation. This approach identified a conserved double-stranded beta-helix (DSBH) fold and a HxDxnH facial triad as structural motifs. Moreover, our systematic annotation in nine species identified 313 DSBH fold-containing proteins that split into 25 highly conserved subgroups. We give further evidence that Jmjd6 most likely has a function as a nonheme-Fe(II)-2-oxoglutarate-dependent dioxygenase as previously suggested. Further, we provide novel insights into the evolution of Jmjd6 and other related members of the superfamily of JmjC domain containing proteins. Finally, we discuss possibilities of the involvement of Jmjd6 and 1110005A03Rik in an antagonistic biochemical pathway.


Differential effects of light and feeding on circadian organization of peripheral clocks in a forebrain Bmal1 mutant.
In order to assess the contribution of a central clock in the hypothalamic suprachiasmatic nucleus (SCN) to circadian behavior and the organization of peripheral clocks, we generated forebrain/SCN-specific Bmal1 knockout mice by using floxed Bmal1 and pan-neuronal Cre lines. The forebrain knockout mice showed >90% deletion of BMAL1 in the SCN and exhibited an immediate and complete loss of circadian behavior in constant conditions. Circadian rhythms in peripheral tissues persisted but became desynchronized and damped in constant darkness. The loss of synchrony was rescued by light/dark cycles and partially by restricted feeding (only in the liver and kidney but not in the other tissues) in a distinct manner. These results suggest that the forebrain/SCN is essential for internal temporal order of robust circadian programs in peripheral clocks, and that individual peripheral clocks are affected differently by light and feeding in the absence of a functional oscillator in the forebrain.


Protective effects of curcumin and vitamin E against chlorpyrifos-induced lung oxidative damage.
There are increasing concerns regarding the toxic effects of chlorpyrifos (CPF) on human health. Curcumin (CUR) is a yellow pigment isolated from turmeric ground rhizome of Curcuma longa Linn., which has been identified as an antioxidant agent. This study was designed to examine the protective effect of CUR and vitamin E (Vit E) on CPF-induced lung toxicity. Rats were divided into seven groups: control, CPF (13.5 mg/kg, orally), CPF + CUR (100 and 300 mg/kg, respectively, orally), CPF + α-tocopherol (Vit E, 150 mg/kg, intraperitoneally), CPF and CUR (100 and 300 mg/kg, respectively) in combination with α-tocopherol. The regimens were administered once daily for 28 days. At the end of the treatment period, lungs were collected for evaluation of oxidative factors and histopathological parameters. CUR and Vit E led to a decrease in lipid peroxidation in the lungs of the CPF-injected animals (48% and 51%, respectively). Glutathione peroxidase inhibited by CPF (91.9 nmol/min/mg protein) was induced again by CUR and Vit E (167.1 and 171.8 nmol/min/mg protein). CUR and Vit E caused a significant induction of superoxide dismutase (103.4 U/mg protein). Catalase activity almost returned to normalcy in CPF-intoxicated rats subjected to CUR + Vit E treatment (p < 0.001). Lung sections from CPF-treated rats displayed histopathological damages, while coadministration of CUR and Vit E resulted in apparently normal morphology with a significant decrease in injuries (p < 0.05). Our findings revealed that coadministration of Vit E and CUR to CPF-treated animals prevents the oxidative damages in the lung tissues.


Prevalence of intellectual disabilities in Norway: Domestic variance.
Based on national registers, the prevalence of intellectual disability (ID) in Norway is estimated to be 0.44 per 100 inhabitants. This study aimed to examine geographic and urban-rural differences in the prevalence of ID in Norway. Methods A survey based on the national register. Financial transfers intended to provide equal services to people with ID are based on these reports. Results A higher prevalence was found in the North region of Norway. A negative correlation between the population density and the prevalence of ID was also found. Conclusion There was considerable geographic and urban-rural differences in the prevalence of ID, which may be attributable to not only the large diversity of services, but also some other factors. The results were discussed with respect to the deinstitutionalisation progress, resource-intensive services and costs. Differences also reflect some problems in diagnosing ID in people having mild ID.


Increased virulence of an epidemic strain of Mycobacterium massiliense in mice.
Chronic pulmonary disease and skin/soft tissue infections due to non-tuberculous mycobacteria (NTM) of the Mycobacterium chelonae-abscessus-massiliense group is an emerging health problem worldwide. Moreover, the cure rate for the infections this group causes is low despite aggressive treatment. Post-surgical outbreaks that reached epidemic proportions in Brazil recently were caused by M. massiliense isolates resistant to high-level disinfection with glutaraldehyde (GTA). Understanding the differences in the virulence and host immune responses induced by NTM differing in their sensitivity to disinfectants, and therefore their relative threat of causing outbreaks in hospitals, is an important issue. We compared the replication and survival inside macrophages of a GTA-susceptible reference Mycobacterium massiliense clinical isolate CIP 108297 and an epidemic strain from Brazil, CRM-0019, and characterized the immune responses of IFNγ knockout mice exposed to a high dose aerosol with these two isolates. CRM-0019 replicated more efficiently than CIP 108297 inside mouse bone marrow macrophages. Moreover, the animals infected with CRM-0019 showed a progressive lung infection characterized by a delayed influx of CD4+ and CD8+ T cells, culminating in extensive lung consolidation and demonstrated increased numbers of pulmonary CD4+ Foxp3+ regulatory T cells compared to those infected with the reference strain. Immunosuppressive activity of regulatory T cells may contribute to the progression and worsening of NTM disease by preventing the induction of specific protective immune responses. These results provide the first direct evidence of the increased virulence in macrophages and mice and pathogenicity in vivo of the Brazilian epidemic isolate and the first observation that NTM infections can be associated with variable levels of regulatory T cells which may impact on their virulence and ability to persist in the host.


Role of the Streptococcus mutans irvA gene in GbpC-independent, dextran-dependent aggregation and biofilm formation.
Dextran-dependent aggregation (DDAG) of Streptococcus mutans is an in vitro phenomenon that is believed to represent a property of the organism that is beneficial for sucrose-dependent biofilm development. GbpC, a cell surface glucan-binding protein, is responsible for DDAG in S. mutans when cultured under defined stressful conditions. Recent reports have described a putative transcriptional regulator gene, irvA, located just upstream of gbpC, that is normally repressed by the product of an adjacent gene, irvR. When repression of irvA is relieved, there is a resulting increase in the expression of GbpC and decreases in competence and synthesis of the antibiotic mutacin I. This study examined the role of irvA in DDAG and biofilm formation by engineering strains that overexpressed irvA (IrvA+) on an extrachromosomal plasmid. The IrvA+ strain displayed large aggregation particles that did not require stressful growth conditions. A novel finding was that overexpression of irvA in a gbpC mutant background retained a measure of DDAG, albeit very small aggregation particles. Biofilms formed by the IrvA+ strain in the parental background possessed larger-than-normal microcolonies. In a gbpC mutant background, the overexpression of irvA reversed the fragile biofilm phenotype normally associated with loss of GbpC. Real-time PCR and Northern blot analyses found that expression of gbpC did not change significantly in the IrvA+ strain but expression of spaP, encoding the major surface adhesin P1, increased significantly. Inactivation of spaP eliminated the small-particle DDAG. The results suggest that IrvA promotes DDAG not only by GbpC, but also via an increase in P1.


Climate change and the green energy paradox: the consequences for twaite shad Alosa fallax from the River Severn, U.K.
A stock-recruitment model with a temperature component was used to estimate the effect of an increase in temperature predicted by climate change projections on population persistence and distribution of twaite shad Alosa fallax. An increase of 1 and 2° C above the current mean summer (June to August) water temperature of 17·8° C was estimated to result in a three and six-fold increase in the population, respectively. Climate change is also predicted to result in an earlier commencement to their spawning migration into fresh water. The model was expanded to investigate the effect of any additional mortality that might arise from a tidal power barrage across the Severn Estuary. Turbine mortality was separated into two components: (1) juvenile (pre-maturation) on their out migration during their first year and on their first return to the river to spawn and (2) post-maturation mortality on adults on the repeat spawning component of the population. Under current conditions, decreasing pre-maturation and post-maturation survival by 8% is estimated to result in the stock becoming extinct. It is estimated that an increase in mean summer water temperature of 1° C would mean that survival pre and post-maturation would need to be reduced by c. 10% before the stock becomes extinct. Therefore, climate change is likely to be beneficial to populations of A. fallax within U.K. rivers, increasing survival and thus, population persistence.


Cation transport functions in vitro in patients with untreated essential hypertension: a comparison of erythrocytes and leucocytes.
We have measured intracellular sodium concentrations and specific 3H-labelled glycoside binding characteristics in the erythrocytes and leucocytes of patients with untreated essential hypertension, and have compared the results with those in well-matched normotensive control subjects. Intracellular sodium concentrations were increased in the leucocytes, but not in the erythrocytes, of patients with untreated essential hypertension. There were no differences in the 3H-labelled glycoside binding characteristics of either the erythrocytes or the leucocytes of hypertensive and normotensive subjects. There was no difference in the ability of plasma samples from hypertensive and normotensive subjects to inhibit the binding of [3H]-ouabain to intact leucocytes from normotensive subjects. These findings are not consistent with the presence of increased concentrations of a substance which behaves like a cardiac glycoside in the circulation of patients with untreated essential hypertension.


The value of routine preoperative medical testing before cataract surgery. Study of Medical Testing for Cataract Surgery.
Routine preoperative medical testing is commonly performed in patients scheduled to undergo cataract surgery, although the value of such testing is uncertain. We performed a study to determine whether routine testing helps reduce the incidence of intraoperative and postoperative medical complications. We randomly assigned 19,557 elective cataract operations in 18,189 patients at nine centers to be preceded or not preceded by a standard battery of medical tests (electrocardiography, complete blood count, and measurement of serum levels of electrolytes, urea nitrogen, creatinine, and glucose), in addition to a history taking and physical examination. Adverse medical events and interventions on the day of surgery and during the seven days after surgery were recorded. Medical outcomes were assessed in 9408 patients who underwent 9626 cataract operations that were not preceded by routine testing and in 9411 patients who underwent 9624 operations that were preceded by routine testing. The most frequent medical events in both groups were treatment for hypertension and arrhythmia (principally bradycardia). The overall rate of complications (intraoperative and postoperative events combined) was the same in the two groups (31.3 events per 1000 operations). There were also no significant differences between the no-testing group and the testing group in the rates of intraoperative events (19.2 and 19.7, respectively, per 1000 operations) and postoperative events (12.6 and 12.1 per 1000 operations). Analyses stratified according to age, sex, race, physical status (according to the American Society of Anesthesiologists classification), and medical history revealed no benefit of routine testing. Routine medical testing before cataract surgery does not measurably increase the safety of the surgery.


Life events and psychiatric symptoms in adults with intellectual disabilities.
Previous research has indicated that children and adults with intellectual disabilities (ID) may respond to traumatic and other life events in a similar way to the general population. However, few studies have charted the extent of exposure to recent life events in samples of adults with ID and the association of such exposure with general psychiatric problems. Adults with ID (n = 1155) in community and residential services in a county district in North-east England were assessed using the Psychiatric Assessment for Adults with Developmental Disabilities Checklist (PAS-ADD Checklist), which includes a checklist of recent life events. Data were provided by informants who knew the index client well. Within the 12 months before data collection, the five most frequently experienced life events were: moving residence (15.5% of sample), serious illness of close relative or friend (9.0%), serious problem with close friend, neighbour or relative (8.8%), serious illness or injury to self (8.5%), and death of close family friend or other relative (8.3%). Overall, 46.3% had experienced one or more significant life events in the previous 12 months and 17.4% had experienced two or more. Logistic regression analysis revealed that the presence of one or more life events in the previous 12 months added significantly to the classification of psychiatric caseness predicted by demographic variables (age, sex, residence in community or hospital) on the PAS-ADD Affective Disorder scale. Overall, the odds ratio for affective disorder given exposure to one or more life events was 2.23 [95% confidence interval (CI) = 1.56, 3.18]. Small, but potentially significant relationships were found between life events exposure and psychiatric problems in adults with ID. Further research is needed to explore the causal direction of this relationship and also to develop more sensitive measures of life events relevant to the situation of adults in residential and community service environments.


Lung metastasis from TTF-1 positive sigmoid adenocarcinoma. pitfalls and management.
The lung is a frequent site of metastatic involvement, and in many cases the differential diagnosis between a metastasis and a primary carcinoma is a substantial question. TTF-1 is considered as a reliable marker for differential diagnosis in distinguishing primary lung carcinoma and metastasis, especially when dealing with an adenocarcinoma or a large-cell carcinoma. It was generally thought that adenocarcinomas arising in the gastrointestinal tract do not express TTF-1. Recently, it has been reported that a small percentage (1.8%-5.8%) of intestinal adenocarcinoma TTF-1 positive show differences in sensitivity/specificity depending on the antibody clones. We report a case of lung localization of a TTF-1 positive adenocarcinoma in a patient with a history of colon adenocarcinoma. Based on the current results and previous reports, we propose the following criteria for diagnosing lung metastasis from TTF-1 positive intestinal adenocarcinoma. 1) Clinical features and anamnestic history are diagnostic milestones, and provide very important information as a prognostic parameter of primary carcinoma and the time interval between the two localizations (primary and metastasis). 2) The histologic features are compatible with an enteric differentiation. 3) TTF-1 must be tested in the primary carcinoma. 4) In lung lesions, in association with TTF-1, it could be useful to test other immunohistochemical markers such as CDX-2 and NapsinA. 5) Testing other immunohistochemical or molecular markers in either lesion is not very useful. Heterogeneity between primary and metastatic lesions has been reported in the literature. Application of the above-mentioned criteria would simplify diagnosis of lung metastases from TTF-1 positive intestinal adenocarcinoma.


Long-term visual and microperimetry outcomes following autologous retinal pigment epithelium choroid graft for neovascular age-related macular degeneration.
To describe the 2- to 4-year visual and microperimetry outcomes of autologous retinal pigment epithelium (RPE)-choroid graft in patients with neovascular age-related macular degeneration (AMD). In this retrospective cohort study, 12 patients with subfoveal neovascular AMD who had undergone autologous RPE-choroid graft between August 2004 and June 2005 were reviewed. Change in visual acuity (VA), contrast sensitivity (CS), fixation stability and retinal sensitivity on microperimetry after 2-3 years and the rates of late postoperative complications were examined. Patients were followed for 26-48 months (mean, 39). Median preoperative VA (logMAR) was 0.87 but declined to 1.43 (1 year), 1.46 (2 years) and 1.38 (3 years), P = 0.001. Median CS (logCS) was 0.75 preoperatively but declined to 0.45 at 2 years. Six patients had serial microperimetry. Fixation stability declined in 1 but improved in 2 patients. All 6 had decline in retinal sensitivity over the graft during follow up. Retinal detachment did not occur after 12 months but 8 developed epiretinal membrane, 12 had cystic retinal change over the graft and 4 developed recurrent choroidal neovascularization. However, 10 grafts retained autofluorescence signal at 18-48 months of follow up. Autologous RPE-choroid graft can maintain VA, stable fixation and retinal sensitivity in some patients for over 3 years. The spatial correlation between graft autofluorescence, outer retinal structures on optical coherence tomography and retinal sensitivity are consistent with photoreceptor cell rescue. However, we caution the use of this technique as there is high complication rate and delayed loss of retinal function.


Resveratrol ameliorates high-fat diet-induced insulin resistance and fatty acid oxidation via ATM-AMPK axis in skeletal muscle.
Resveratrol (RSV) is a polyphenolic phytoalexin that exhibits diverse pharmacological actions, including its effect on the insulin resistance. However, the mechanism through which RSV improves insulin resistance is not fully understood yet. The aim of this study was to determine the mechanism through which RSV ameliorates insulin resistance in skeletal muscle of high-fat diet (HFD)-induced mouse model, as well as palmitic acid (PA) treated L6 cells, with a specific focus on the response of RSV on fatty acid oxidation. Male C57BL6/J mice were randomly divided into three groups: normal diet-fed mice (ND), the high-fat diet-fed mice (HFD), HFD supplemented with RSV (100 mg/kg body weight [BW]/day orally; n = 10). Fasting plasma glucose, insulin, total cholesterol, triglyceride (TG), and free fatty acid levels were determined. The intraperitoneal glucose tolerance test was used to measure blood glucose and area under the curve. The quantitative insulin sensitivity index was calculated to assess insulin resistance. Skeletal muscles were collected for histology study and protein expression measurement. L6 cells were cultured with PA and the glucose concentration in the culture medium, and the intracellular TG levels were tested. RSV, chloroquine, palmitoyltransferase and Ku-55933 were administered to differentiate L6 cells. The HFD fed mice showed increased BW, hyperglycemia, and hyperlipidemia. The expressions of ataxia telangiectasia mutated (ATM), 5' adenosine monophosphate-activated protein kinase (AMPK), carnitine palmitoyltransferase 1, cytochrome oxidase subunit IV protein were significantly decreased in the skeletal muscles of HFD fed mice and PA-treated L6 cells. All these effects induced by HFD and PA were reversed by RSV treatment. ATM is a key factor to improve HFD-induced lipid metabolism and insulin resistance in skeletal muscles. The effects of RSV on ameliorating HFD-induced abnormal lipid metabolism and insulin resistance mediated through ATM-AMPK pathway may due to its improvement in fatty acid oxidation efficiency and sequential reduction in ROS production in skeletal muscle. These results provide important theoretical evidence for the application of RSV in the prevention and treatment of diabetes mellitus and related metabolic diseases.


Complex contributions of Ets2 to craniofacial and thymus phenotypes of trisomic "Down syndrome" mice.
Ts65Dn mice have segmental trisomy for orthologs of about half of the genes on human chromosome 21, including Ets2. These mice develop anomalies of the cranial skeleton and thymus that parallel those in Down syndrome. Overexpression of the Ets2 transcription factor gene was posited to be sufficient to produce these craniofacial and thymus deficits in transgenic mice that constitutively overexpress a processed Ets2 transcript under a promiscuous promoter [Sumarsono et al. (1996); Nature 379:534-537; Wolvetang et al. (2003); Hum Mol Genet 12:247-255]. Evaluation of trisomic mice with varying copy numbers of a properly regulated Ets2 gene indicated increased dosage of Ets2 was not sufficient to produce effects on thymus and most of the cranial anomalies seen in Ts65Dn mice. However, mesoderm-derived cranial skeletal elements are significantly more affected in Ts65Dn, Ets2(+/-) mice compared to Ts65Dn littermates suggesting a differential interaction of Ets2-related processes with mesoderm-derived and neural crest-derived formative tissues. Our results support the growing evidence for interactions among multiple genes contributing to developmental perturbations resulting in variation in complex Down syndrome phenotypes.


Crystal structure of a glycosylated Fab from an IgM cryoglobulin with properties of a natural proteolytic antibody.
The 2.6 A (1 A=0.1 nm) resolution structure has been determined for the glycosylated Fab (fragment antigen binding) of an IgM (Yvo) obtained from a subject with Waldenström's macroglobulinaemia. Dynamic light scattering was used to estimate the gel point and monitor the formation of an ordered hydroscopic gel of Yvo IgM upon cooling. If a cryoglobulin forms gels in peripheral tissues and organs, the associated swelling and damage to microvasculature can result in considerable morbidity and mortality. The three-dimensional structure of the branched N-linked oligosaccharide associated with the CH1 domain (first constant domain of heavy chain) is reported. The carbohydrate may act to shield part of the lateral surface of the CH1 domain and crowd the junction between the CH1 and CH2 domains, thereby limiting the segmental flexibility of the Fab arms in intact Yvo IgM, especially at low temperatures. Recently, Yvo IgM was shown to have the properties of a naturally occurring proteolytic antibody [Paul, Karle, Planque, Taguchi, Salas, Nishiyama, Handy, Hunter, Edmundson and Hanson (2004) J. Biol. Chem. 279, 39611-39619; Planque, Bangale, Song, Karle, Taguchi, Poindexter, Bick, Edmundson, Nishiyama and Paul (2004) J. Biol Chem. 279, 14024-14032]. The Yvo protein displayed the ability to cleave, by a nucleophilic mechanism, the amide bonds of a variety of serine protease substrates and the gp120 coat protein of HIV. An atypical serine, arginine and glutamate motif is located in the middle of the Yvo antigen-binding site and displays an overall geometry that mimics the classical serine, histidine and aspartate catalytic triad of serine proteases. Our present findings indicate that pre-existing or natural antibodies can utilize at least one novel strategy for the cleavage of peptide bonds.


Postoperative spinal epidural hematoma after microscopic lumbar decompression: a prospective magnetic resonance imaging study in 89 patients.
A prospective case series. To prospectively analyze the incidence, characteristics, clinical outcomes, and risk factors of postoperative spinal epidural hematoma (SEH) after microscopic lumbar decompression using magnetic resonance imaging (MRI). Studies prospectively focusing on postoperative SEH after microscopic lumbar decompression alone are rare. Eighty-nine patients who underwent microscopic lumbar decompressive surgery for herniated disc and/or stenosis between January 2007 and June 2007 were prospectively followed. Decompression was carried out using unilateral or bilateral laminotomy in all patients. Postoperative MRI was taken at 24 hours after surgery in all patients. Using operative report, chart, and MRI, the incidence, characteristics, and risk factors of postoperative SEH were evaluated. Clinical outcomes were evaluated 2 years after surgery using Visual Analogue Scale score and Oswestry Disability Index. Postoperative SEH developed in 13 patients (14.6%). There were 5 males and 8 females. The mean age of these patients was 57.1 years. Postoperative SEH occurred at the index level in 6 cases, and at the index level with extension toward non-decompressed adjacent levels in 7 cases. Eleven patients were asymptomatic and 2 patients complained of leg pain and/or mild weakness. No patients underwent revision surgery owing to postoperative SEH. There was no significant difference in improvements of Visual Analogue Scale and ODI scores, and clinical success rate between patients with and without SEH. Patient's age 50 years old or more was the only significant risk factor for the development of postoperative SEH (P=0.024; odds ratio=5.12). The incidence of postoperative SEH after microscopic lumbar decompressive surgery was 14.6%. Postoperative SEH did not delay clinical improvements. Age 50 years old or more was strongly associated with the development of postoperative SEH.


Comparative Associations of Street Network Design, Streetscape Attributes and Land-Use Characteristics on Pedestrian Flows in Peripheral Neighbourhoods.
Research has sufficiently documented the built environment correlates of walking. However, evidence is limited in investigating the comparative associations of micro- (streetscape features) and macro-level (street network design and land-use) environmental measures with pedestrian movement. This study explores the relative association of street-level design-local qualities of street environment-, street network configuration -spatial structure of the urban grid- and land-use patterns with the distribution of pedestrian flows in peripheral neighbourhoods. Street design attributes and ground-floor land-uses are obtained through field surveys while street network configuration is evaluated through space syntax measures. The statistical models indicate that the overall spatial configuration of street network proves to be a stronger correlate of walking than local street-level attributes while only average sidewalk width appears to be a significant correlate of walking among the streetscape measures. However, the most significant and consistent correlate of the distribution of flows is the number of recreational uses at the segment-level. This study contributes to the literature by offering insights into the comparative roles of urban design qualities of the street environment and street network layout on pedestrian movement. The findings also offer evidence-based strategies to inform specific urban design and urban master planning decisions (i.e., the provision of more generous sidewalks on streets with relatively higher directional accessibility) in creating lively, walkable environments.


Prevention of thyroidectomy scar using a new 1,550-nm fractional erbium-glass laser.
Surgical scars are a common cosmetic problem that occurs in various surgical fields including dermatology. Diverse trials have been made to prevent this annoying scar formation. Recently, 585- and 595-nm pulsed dye laser irradiation presented satisfactory cosmetic outcome for the treatment of surgical scars. Other fractionated lasers or light devices were also applied for scar treatment. To determine the effectiveness and safety of a newly developed 1,550-nm fractional erbium-glass laser in the prevention of scar formation after total thyroidectomy. Twenty-seven ethnic South Korean patients with linear surgical suture lines after total thyroidectomy operation were treated with a 1,550-nm fractional erbium-glass laser. The same surgeon performed all of the operations using the same surgical techniques. Each patient was treated four times at 1-month intervals using the same parameters (5- x 10-mm spot size, 10 mJ, 1,500 spot/cm(2), static mode). Initiation of the first irradiation was made approximately 2 to 3 weeks after the thyroidectomy. The scar prevention effects were evaluated each month for 6 months after thyroidectomy. Two kinds of assessment methods were applied in this evaluation. First, the Vancouver Scar Scale (VSS) was used. Second, three independent physicians gave a global assessment valuation to the final cosmetic results: poor (1), fair (2), good (3), or excellent (4). These results were compared with the surgical scars of a control group (patients who denied laser treatments and had no other treatments during the 6 months after total thyroidectomy by the same surgeon). The average VSS score was lower in the laser treatment group. The global assessment also presented better cosmetic outcomes in the treatment group than in the controls. A new 1,550-nm fractional erbium-glass laser may efficiently repress the formation and hypertrophy of thyroidectomy scars on the neck, and it can be safely applied in relatively dark Asian skin without noticeable adverse effects.


A Scoping Review of Technological Approaches to Environmental Monitoring.
Indoor environment quality (IEQ) can negatively affect occupant health and wellbeing. Air quality, as well as thermal, visual and auditory conditions, can determine how comfortable occupants feel within buildings. Some can be measured objectively, but many are assessed by interpreting qualitative responses. Continuous monitoring by passive sensors may be useful to identify links between environmental and physiological changes. Few studies localise measurements to an occupant level perhaps due to many environmental monitoring solutions being large and expensive. Traditional models for occupant comfort analysis often exacerbate this by not differentiating between individual building occupants. This scoping review aims to understand IEQ and explore approaches as to how it is measured with various sensing technologies, identifying trends for monitoring occupant health and wellbeing. Twenty-seven studies were reviewed, and more than 60 state-of-the-art and low-cost IEQ sensors identified. Studies were found to focus on the home or workplace, but not both. This review also found how wearable technology could be used to augment IEQ measurements, creating personalised approaches to health and wellbeing. Opportunities exist to make individuals the primary unit of analysis. Future research should explore holistic personalised approaches to health monitoring in buildings that analyse the individual as they move between environments.


7-Farnesyloxycoumarin Exerts Anti-cancer Effects on a Prostate Cancer Cell Line by 15-LOX-1 Inhibition.
Prostate cancer is one of the leading causes of cancer related deaths in males worldwide. Overexpression of 15-lipoxygenase-1 (15-LOX-1) enzyme and high activity of its metabolic pathway is reported to be a driver for prostate cancer malignancy. Farnesyloxycoumarin derivatives (3f, 4f and 7f) inhibit lipoxygenase enzyme. We hypothesized that farnesyloxycoumarins may exert an anti-cancer effect on prostate cancer cells due to their 15-LOX-1 inhibitory potential. The enzyme inhibitory activity of 3f, 4f and 7f was initially evaluated on PC-3 and DU145 prostate cancer cell lines. MTT assay was performed on cancer cell lines and HFF3 cell line to assess cytotoxicity of the compounds. The apoptotic morphology of cells after treatments was assessed by DAPI staining and single cell gel electrophoresis. Propidium iodide staining was also performed to detect cell cycle variations after treatment. 7f inhibited 15-LOX-1 at IC50=4.3 µg/mL, while 3f and 4f did not show high inhibitory activity. 7f reduced cell viability in PC-3 cells at IC50=22-31 µg/mL, however, no significant cytotoxicity was revealed on normal cells. DAPI staining and comet assay confirmed apoptosis and DNA damage in PC-3 cells after 7f treatment, while flow cytometry results revealed G1 arrest in PC-3 cells. The results are indicative of a distinctive cytotoxic mechanism for 7f compared to other coumarins, possibly due to its 15-LOX-1 inhibitory potential. Thus, this compound is valued for further assessments with the aim of developing a promising targeted therapy for prostate cancer patients.


Maintenance of Acromegaly Control in Patients Switching From Injectable Somatostatin Receptor Ligands to Oral Octreotide.
The phase 3 CHIASMA OPTIMAL trial (NCT03252353) evaluated efficacy and safety of oral octreotide capsules (OOCs) in patients with acromegaly who previously demonstrated biochemical control while receiving injectable somatostatin receptor ligands (SRLs). In this double-blind study, patients (N = 56) stratified by prior SRL dose were randomly assigned 1:1 to OOC or placebo for 36 weeks. The primary end point was maintenance of biochemical control at the end of treatment (mean insulin-like growth factor 1 [IGF-1] ≤ 1.0 × upper limit of normal [ULN]; weeks 34 and 36). Time to loss of IGF-1 response and proportion requiring reversion to injectable SRLs were assessed as broader control measures. Mean IGF-1 measurements were 0.80 and 0.97 × ULN for OOC and 0.84 and 1.69 × ULN for placebo, at baseline and end of treatment, respectively. Mean growth hormone (GH) changed from 0.66 to 0.60 ng/mL for OOCs and 0.90 to 2.57 ng/mL for placebo. Normalization of IGF-1 levels (≤ 1.0 × ULN) was maintained in 58.2% for OOCs vs 19.4% for placebo (P = .008); GH levels were maintained (< 2.5 ng/mL) in 77.7% for OOC vs 30.4% for placebo (P = .0007). Median time to loss of response (IGF-1 > 1.0 or ≥ 1.3 × ULN definitions) for patients receiving placebo was 16 weeks; for patients receiving OOCs, it was not reached for both definitions during the 36-week trial (P < .0001). Of the patients in the OOC group, 75% completed the trial on oral therapy. The OOC safety profile was consistent with previous SRL experience. OOCs may be an effective therapy for patients with acromegaly who previously were treated with injectable SRLs.


Infusion of beta-endorphin improves insulin resistance in fructose-fed rats.
In an attempt to probe the effect of beta-endorphin on insulin resistance, we used Wistar rats that were fed fructose-rich chow to induce insulin resistance. Insulin action on glucose disposal rate (GDR) was measured using the hyperinsulinemic euglycemic clamp technique, in which glucose (variable), insulin (40 mU/kg/min), and beta-endorphin (6 ng/kg/min) or vehicle were initiated simultaneously and continued for 120 min. A marked reduction in insulin-stimulated GDR was observed in fructose-fed rats compared to normal control rats. Infusion of beta-endorphin reversed the value of GDR, which was inhibited by naloxone and naloxonazine each at doses sufficient to block opioid mu-receptors. Opioid mu-receptors may therefore be activated by beta-endorphin to improve insulin resistance. Next, soleus muscle was isolated to investigate the effect of beta-endorphin on insulin signals. Insulin resistance in rats induced by excess fructose was associated with the impaired insulin receptor (IR), tyrosine autophosphorylation, and insulin receptor substrate (IRS)-1 protein content in addition to the significant decrease in IRS-1 tyrosine phosphorylation in soleus muscle. This impaired glucose transportation was also due to signaling defects that included an attenuated p85 regulatory subunit of phosphatidylinositol 3-kinase (PI3-kinase) and Akt serine phosphorylation. However, IR protein levels were not markedly changed in rats with insulin resistance. beta-endorphin infusion reversed the fructose-induced decrement in the insulin-signaling cascade with increased GDR. Apart from IR protein levels, infusion of beta-endorphin reversed the decrease in protein expression for the IRS-1, p85 regulatory subunit of PI3-kinase, and Akt serine phosphorylation in soleus muscle in fructose-fed rats. The decrease in insulin-stimulated protein expression of glucose transporter subtype 4 (GLUT 4) in fructose-fed rats returned to near-normal levels after beta-endorphin infusion. Infusion of beta-endorphin may improve insulin resistance by modulating the insulin-signaling pathway to reverse insulin responsiveness.


PTSD symptom clusters associated with short- and long-term adjustment in early diagnosed breast cancer patients.
We performed an observational prospective cohort study to investigate post-traumatic stress symptoms, emerging after cancer diagnosis, which could influence patients' short- and long-term adjustment to illness, in order to foster screening measures and management of psychological factors in daily clinical pathways. Patients' post-traumatic stress symptoms, psychological well-being and perceived quality of life were assessed through standardised questionnaires. The Profile of Mood States questionnaire was administered at pre-operative assessment (T0), surgical admission (T1) and discharge from hospital (T2). The Impact of Event Scale and the State-Trait Anxiety Inventory were administered at T0, T1, T2 and 2 years after discharge (T3). At 2-year follow-up, women were also asked to rate their perceived quality of life on a 0-10 visual analogue scale. Between January 2014 and April 2015, 150 women were enrolled. Results showed that more than 90% of patients experienced post-traumatic stress symptoms after cancer diagnosis (14% with severe symptoms and 76.7% with moderate symptoms) and post-traumatic stress disorder (PTSD) symptoms that persisted up to the 2-year from discharge follow-up, with significant improvement only 2 years after hospital discharge. In particular, mediation models showed that intrusive thoughts impede mood adjustment to the disease during the pre-surgical phase, with anxiety amplifying the negative effect, while symptoms of avoidance are more detrimental in the long term for patients' quality of life. PTSD symptom clusters have different influence on short- and long-term reaction to illness. Based on this evidence, appropriate interventions to manage PTSDs in the context of oncology should be developed.


Oxygen diffusion in ceria doped with rare-earth elements.
We examine the effects of the dopant type and the dopant distribution on the ion diffusion in ceria doped with rare-earth elements (Pr, Nd, Pm, Sm, Eu, and Gd). Diffusion is simulated by means of a Kinetic Monte Carlo method using input transition rates derived from diffusion barriers calculated in the framework of density functional theory (DFT). Based on diffusion simulations, we discuss the characteristics of the dopants in terms of the diffusion barriers, and study oxygen ion trajectories for different dopants and distributions. Our simulations show a trend of increasing ion diffusivity with increasing atomic number for all distributions.


Synthesis and characterisation of rylene diimide dimers using molecular handcuffs.
A strategy for positioning, and loosely connecting, molecules in close proximity using mechanically interlocked handcuffs is described. The strategy is demonstrated using rylene diimides, creating dimeric structures in which two components are linked through pillar[5]arene/imidazolium rotaxanes. Investigation of the resulting molecules demonstrates intriguing and new properties that arise from placing these redox active dye molecules together, allowing interactions, whilst allowing the molecules to separate as required. In particular we observe excimer emission from a perylene diimide dimer handcuff and the formation of an unusual radical anion π-dimer upon double reduction of the same molecule. The latter exhibits a unique visible absorption profile for a PDI-based molecule. We demonstrate the flexibility of our approach by making an unprecedented mixed perylene diimide/naphthalene diimide dimer which also reveals interactions between the two components. Our synthetic strategy facilitates the creation of unusual dimeric structures and allows the investigation of intermolecular interactions and the effects they have on electronic and magnetic properties.


Plankton biogeography in the North Atlantic Ocean and its adjacent seas: Species assemblages and environmental signatures.
Plankton biodiversity is a key component of marine pelagic ecosystems. They are at the base of the food web, control the productivity of marine ecosystems, and provide many provisioning and regulating ecological services. It is therefore important to understand how plankton are organized in both space and time. Here, we use data of varying taxonomic resolution, collected by the Continuous Plankton Recorder (CPR) survey, to map phytoplankton and zooplankton biodiversity in the North Atlantic and its adjacent seas. We then decompose biodiversity into 24 species assemblages and investigate their spatial distribution using ecological units and ecoregions recently proposed. Finally, we propose a descriptive method, which we call the environmental chromatogram, to characterize the environmental signature of each plankton assemblage. The method is based on a graphic that identifies where species of an assemblage aggregate along an environmental gradient composed of multiple ecological dimensions. The decomposition of the biodiversity into species assemblages allows us to show (a) that most marine regions of the North Atlantic are composed of coenoclines (i.e., gradients of biocoenoses or communities) and (b) that the overlapping spatial distribution of assemblages is the result of their environmental signatures. It follows that neither the ecoregions nor the ecological units identified in the North Atlantic are characterized by a unique assemblage but instead by a mosaic of assemblages that overlap in many places.


Demographics, Treatments, and Outcomes of Acute Respiratory Distress Syndrome: the Focused Outcomes Research in Emergency Care in Acute Respiratory Distress Syndrome, Sepsis, and Trauma (FORECAST) Study.
Acute respiratory distress syndrome (ARDS) remains a major cause of death. Epidemiology should be continually examined to refine therapeutic strategies for ARDS. We aimed to elucidate demographics, treatments, and outcomes of ARDS in Japan. This is a prospective cohort study for ARDS. We included adult patients admitted to intensive care units through emergency and critical care departments who satisfied the American-European Consensus Conference (AECC) acute lung injury (ALI) criteria. In addition, the fulfillment of the Berlin definition was assessed. Logistic regression analyses were used to examine the association of independent variables with outcomes. Our study included 166 patients with AECC ALI from 34 hospitals in Japan; among them, 157 (94.6%) fulfilled the Berlin definition. The proportion of patients with PaO2/FIO2 ≤ 100, patients under invasive positive pressure ventilation (IPPV), and in-hospital mortality was 39.2%, 92.2%, and 38.0% for patients with AECC ALI and 38.9%, 96.8%, and 37.6% for patients with Berlin ARDS, respectively. The area of lung infiltration was independently associated with outcomes of ARDS. Low-mid-tidal volume ventilation was performed in 75% of patients under IPPV. Glucocorticoid use was observed in 54% patients, and it was positively associated with mortality. Our study included a greater percentage of patients with ARDS with high severity and found that the overall mortality was 38%. The management of ARDS in Japan was characterized by high the utilization rate of glucocorticoids, which was positively associated with mortality.


Sparseness prior based iterative image reconstruction for retrospectively gated cardiac micro-CT.
Recent advances in murine cardiac studies with three-dimensional (3D) cone beam micro-CT used a retrospective gating technique. However, this sampling technique results in a limited number of projections with an irregular angular distribution due to the temporal resolution requirements and radiation dose restrictions. Both angular irregularity and undersampling complicate the reconstruction process, since they cause significant streaking artifacts. This work provides an iterative reconstruction solution to address this particular challenge. A sparseness prior regularized weighted l2 norm optimization is proposed to mitigate streaking artifacts based on the fact that most medical images are compressible. Total variation is implemented in this work as the regularizer for its simplicity. Comparison studies are conducted on a 3D cardiac mouse phantom generated with experimental data. After optimization, the method is applied to in vivo cardiac micro-CT data.


Gender differences in the neural network of facial mimicry of smiles--An rTMS study.
Under theories of embodied emotion, exposure to a facial expression triggers facial mimicry. Facial feedback is then used to recognize and judge the perceived expression. However, the neural bases of facial mimicry and of the use of facial feedback remain poorly understood. Furthermore, gender differences in facial mimicry and emotion recognition suggest that different neural substrates might accompany the production of facial mimicry, and the processing of facial feedback, in men and women. Here, repetitive transcranial magnetic stimulation (rTMS) was applied to the right primary motor cortex (M1), the right primary somatosensory cortex (S1), or, in a control condition, the vertex (VTX). Facial mimicry of smiles and emotion judgments were recorded in response to video clips depicting changes from neutral or angry to happy facial expressions. While in females rTMS over M1 and S1 compared to VTX led to reduced mimicry and, in the case of M1, delayed detection of smiles, there was no effect of TMS condition for males. We conclude that in female participants M1 and S1 play a role in the mimicry and in the use of facial feedback for accurate processing of smiles.


Rapid, reversible modulation of blood-brain barrier P-glycoprotein transport activity by vascular endothelial growth factor.
Increased brain expression of vascular endothelial growth factor (VEGF) is associated with neurological disease, brain injury, and blood-brain barrier (BBB) dysfunction. However, the specific effect of VEGF on the efflux transporter P-glycoprotein, a critical component of the BBB, is not known. Using isolated rat brain capillaries and in situ rat brain perfusion, we determined the effect of VEGF exposure on P-glycoprotein activity in vitro and in vivo. In isolated capillaries, VEGF acutely and reversibly decreased P-glycoprotein transport activity without decreasing transporter protein expression or opening tight junctions. This effect was blocked by inhibitors of the VEGF receptor flk-1 and Src kinase, but not by inhibitors of phosphatidylinositol-3-kinase or protein kinase C. VEGF also increased Tyr-14 phosphorylation of caveolin-1, and this was blocked by the Src inhibitor PP2. Pharmacological activation of Src kinase activity mimicked the effects of VEGF on P-glycoprotein activity and Tyr-14 phosphorylation of caveolin-1. In vivo, intracerebroventricular injection of VEGF increased brain distribution of P-glycoprotein substrates morphine and verapamil, but not the tight junction marker, sucrose; this effect was blocked by PP2. These findings indicate that VEGF decreases P-glycoprotein activity via activation of flk-1 and Src, and suggest Src-mediated phosphorylation of caveolin-1 may play a role in downregulation of P-glycoprotein activity. These findings also imply that P-glycoprotein activity is acutely diminished in pathological conditions associated with increased brain VEGF expression and that BBB VEGF/Src signaling could be targeted to acutely modulate P-glycoprotein activity and thus improve brain drug delivery.