Iranian infertile couples' strategies to manage social interactions after unsuccessful treatments with assisted reproductive technologies

Many infertile couples feel vulnerable after failed treatment cycles and find insensitive remarks or inappropriate support distressing. They fear that the stress of failed treatment cycles may affect their marriage and lead to marriage breakdown. This study explored the strategies a sample of infertile couples used to manage social interactions after unsuccessful treatment with assisted reproductive technologies. A descriptive qualitative study was conducted with 34 participants including nine infertile couples, nine infertile women and two infertile men with primary infertility, two relatives, and three fertility clinic staff. The participants were selected through purposive sampling at an infertility centre in Iran, between 2016 and 2017. Data were collected using semi-structured face-to-face interviews and analysed by qualitative content analysis approach. Participants found some social interactions after failed assisted reproductive treatment cycles to be distressing and painful. They described tolerating painful emotions which cause them sadness and sorrow as well as feeling embarrassed. As a result, they found they needed to maintain their adopting concealment strategies with their families through not permitting speculation, selective disclosure, not giving details and hiding the truth. This study showed that social interactions following failed assisted reproductive cycles can be upsetting for infertile couples. Couples use different strategies to manage potentially distressing social interactions. Healthcare providers and psychologists may provide a space for safe social interactions in order to help couples to use appropriate strategies in these circumstances

Sex-Based Dimorphism of Anticancer Immune Response and Molecular Mechanisms of Immune Evasion

PURPOSE: We previously demonstrated that sex influences response to immune checkpoint inhibitors. In this article, we investigate sex-based differences in the molecular mechanisms of anticancer immune response and immune evasion in patients with NSCLC. EXPERIMENTAL DESIGN: We analyzed (i) transcriptome data of 2,575 early-stage NSCLCs from seven different datasets; (ii) 327 tumor samples extensively characterized at the molecular level from the TRACERx lung study; (iii) two independent cohorts of 329 and 391 patients, respectively, with advanced NSCLC treated with anti–PD-1/anti–PD-L1 drugs. RESULTS: As compared with men, the tumor microenvironment (TME) of women was significantly enriched for a number of innate and adaptive immune cell types, including specific T-cell subpopulations. NSCLCs of men and women exploited different mechanisms of immune evasion. The TME of females was characterized by significantly greater T-cell dysfunction status, higher expression of inhibitory immune checkpoint molecules, and higher abundance of immune-suppressive cells, including cancer-associated fibroblasts, MDSCs, and regulatory T cells. In contrast, the TME of males was significantly enriched for a T-cell–excluded phenotype. We reported data supporting impaired neoantigens presentation to immune system in tumors of men, as molecular mechanism explaining the findings observed. Finally, in line with our results, we showed significant sex-based differences in the association between TMB and outcome of patients with advanced NSCLC treated with anti–PD-1/PD-L1 drugs. CONCLUSIONS: We demonstrated meaningful sex-based differences of anticancer immune response and immune evasion mechanisms, that may be exploited to improve immunotherapy efficacy for both women and men. TRANSLATIONAL RELEVANCE: It is well known that sex (i.e., the biological differences between men and women) and gender (i.e., behavioral differences associated with being male or female) are variables that affect immune responses to both foreign and selfantigens. Such sex- and gender-based dimorphism of immune system function, in turn reflects complex interactions between genes, hormones, the environment, and commensal microbiome composition. In our previous works, we showed that patients' sex is significantly associated with effectiveness of immune checkpoint inhibitors (ICIs) in patients with several solid tumors, including NSCLC. Here, we identified meaningful differences in molecular mechanisms that drive anticancer immune response as well as in immune evasion mechanisms exploited by NSCLCs arising in men and women. Importantly, we showed that all the findings reported, were not related to other variables potentially associated with sex such as patients' age, stage of disease, tumor histotype, and smoking status. The findings reported in this our work explain our previous clinical observations and can open this area to different immunotherapy strategies in males and females with NSCLC to further improve prognosis of both

Rhetoric and reality: Critical perspective on education in a 3D virtual world

The emergence of any new educational technology is often accompanied by inflated expectations about its potential for transforming pedagogical practice and improving student learning outcomes. A critique of the rhetoric accompanying the evolution of 3D virtual world education reveals a similar pattern, with the initial hype based more on rhetoric than research demonstrating the extent to which rhetoric matches reality. Addressed are the perceived gaps in the literature through a critique of the rhetoric evident throughout the evolution of the application of virtual worlds in education and the reality based on the reported experiences of experts in the field of educational technology, who are all members of the Australian and New Zealand Virtual Worlds Working Group. The experiences reported highlight a range of effective virtual world collaborative and communicative teaching experiences conducted in members’ institutions. Perspectives vary from those whose reality is the actuation of the initial rhetoric in the early years of virtual world education, to those whose reality is fraught with challenges that belie the rhetoric. Although there are concerns over institutional resistance, restrictions, and outdated processes on the one-hand, and excitement over the rapid emergence of innovation on the other, the prevailing reality seems to be that virtual world education is both persistent and sustainable. Explored are critical perspectives on the rhetoric and reality on the educational uptake and use of virtual worlds in higher education, providing an overview of the current and future directions for learning in virtual worlds

Rhetoric and reality: Critical perspective on education in a 3D virtual world

The emergence of any new educational technology is often accompanied by inflated expectations about its potential for transforming pedagogical practice and improving student learning outcomes. A critique of the rhetoric accompanying the evolution of 3D virtual world education reveals a similar pattern, with the initial hype based more on rhetoric than research demonstrating the extent to which rhetoric matches reality. Addressed are the perceived gaps in the literature through a critique of the rhetoric evident throughout the evolution of the application of virtual worlds in education and the reality based on the reported experiences of experts in the field of educational technology, who are all members of the Australian and New Zealand Virtual Worlds Working Group. The experiences reported highlight a range of effective virtual world collaborative and communicative teaching experiences conducted in members’ institutions. Perspectives vary from those whose reality is the actuation of the initial rhetoric in the early years of virtual world education, to those whose reality is fraught with challenges that belie the rhetoric. Although there are concerns over institutional resistance, restrictions, and outdated processes on the one-hand, and excitement over the rapid emergence of innovation on the other, the prevailing reality seems to be that virtual world education is both persistent and sustainable. Explored are critical perspectives on the rhetoric and reality on the educational uptake and use of virtual worlds in higher education, providing an overview of the current and future directions for learning in virtual worlds

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Abstract Background: Elevated total homocysteine (tHcy) levels are associated with an increased risk of cerebrovascular disease. It is uncertain whether tHcy is also an independent risk factor for cognitive impairment. Methods: We examined 95 stroke subjects 3 months after their strokes, and 55 healthy comparison subjects, with a detailed neuropsychological assessment, and MRI brain scans in a proportion (n = 97). Baseline measurements of tHcy, serum folate and B 12 , creatinine and plasma fibrinogen levels were obtained. Results: tHcy levels were higher in the stroke subjects by a mean 34%. These levels were significantly correlated with the first factor of a principal component analysis of the neuropsychological data, after controlling for age, folate, B 12 and creatinine levels. The correlation of Hcy levels was particularly significant with frontal-executive functioning and attention. tHcy levels were significantly correlated with number of infarcts and total stroke volume in the stroke group, but not with T 2 -weighted deep white matter hyperintensity scores, after correction for age. In the control group, tHcy levels were significantly correlated with ventricle-tobrain ratios as measures of brain atrophy. Conclusion: This study provides evidence that high tHcy levels are associated with cognitive impairment, in particular that of frontal-executive function. The major component of this association is accounted for by small and large strokes, but non-vascular neurotoxic effects of tHcy also appear to play a role. tHcy must receive greater attention as a risk factor for cognitive impairment. Copyright © 2003 S. Karger AG, Basel Homocysteine (Hcy) is a sulfur-containing amino acid formed during the metabolism of the essential amino acid methionine. Elevated plasma homocysteine levels were first linked with vascular disease by McCully A high level of Hcy is both proatherogenic and prothrombotic If Hcy promotes cognitive impairment and is a risk factor for AD, it has important epidemiological implications. In this study, we examined plasma Hcy levels in a stroke sample to determine if there was an association between Hcy levels and cognition, and if this could be accounted for by infarct size or small vessel disease as detected by MRI. Methods Sample Subjects (n = 95) were consecutive patients admitted to two large teaching hospitals affiliated with the University of New South Wales who had recently suffered an ischemic stroke as diagnosed by two neurologists, and who met the diagnostic criteria for cerebral infarction Assessment Stroke subjects had a baseline assessment within 1 week of admission which included a detailed medical history and examination, history of risk factors for cerebrovascular disease and dementia, a functional assessment and the Mini-Mental State Examination Homocysteine Measurement Fasting blood was collected and centrifuged within 6 h, and the plasma stored at -20°C for later analysis. Total Hcy was measured using a fluorescence-based immunochemical technique with demonstrated high repeatability Neuropsychological Assessment Premorbid ability was estimated on the basis of performance on the National Adult Reading Test MRI Brain Scans MRI was performed on a proportion of subjects (n = 55 stroke; n = 42 controls) using a 1.5-T Signa GE magnet and the following protocol: a scout mid-sagittal cut (2D, TR 300 ms, TE 14 ms; 5 mm thick, number of excitations 1.5); 1.5-mm-thick T 1 -weighted contiguous coronal sections through whole brain using a FSPGR sequence and 3D acquisition (TR 14.3 ms, TE 5.4 ms); 4-mm-thick T 2 -weighted FLAIR coronal slices through whole brain (TR 8900, TE 145, TI 2200, FOV 25, 256 ! 192). Fifty-three subjects did not receive MRI scans because of claustrophobia or unwillingness to undergo the test. Analysis of Data Neuropsychological Tests. Raw scores were converted to agescaled scores using published norms [24-26, 28, 36, 38-41]. Composite z-scores were obtained for each domain. The raw scores from individual tests were also used in the exploratory analyses. MRI Scans. These were rated by a trained rater with good interrater (Î scores from 0.7 to 0.9 on various measures) and intra-rater (Î 0.8 to 0.9) reliability determined on five scans each. All ratings were carried out on a computer console using ANALYZE (Mayo Foundation) software. Brain infarctions were identified on T 1 -Homocysteine and Cognitive Impairment Dement Geriatr Cogn Disord 2003;15:155-162 15

Effect of sampling effort and sampling frequency on the composition of the planktonic crustacean assemblage: a case study of the river Danube

Although numerous studies have focused on the seasonal dynamics of riverine zooplankton, little is known about its short-term variation. In order to examine the effects of sampling frequency and sampling effort, microcrustacean samples were collected at daily intervals between 13 June and 21 July of 2007 in a parapotamal side arm of the river Danube, Hungary. Samples were also taken at biweekly intervals from November 2006 to May 2008. After presenting the community dynamics, the effect of sampling effort was evaluated with two different methods; the minimal sample size was also estimated. We introduced a single index (potential dynamic information loss; to determine the potential loss of information when sampling frequency is reduced. The formula was calculated for the total abundance, densities of the dominant taxa, adult/larva ratios of copepods and for two different diversity measures. Results suggest that abundances may experience notable fluctuations even within 1 week, as do diversities and adult/larva ratios

Astrocytic Mechanisms Explaining Neural-Activity-Induced Shrinkage of Extraneuronal Space

Neuronal stimulation causes ∼30% shrinkage of the extracellular space (ECS) between neurons and surrounding astrocytes in grey and white matter under experimental conditions. Despite its possible implications for a proper understanding of basic aspects of potassium clearance and astrocyte function, the phenomenon remains unexplained. Here we present a dynamic model that accounts for current experimental data related to the shrinkage phenomenon in wild-type as well as in gene knockout individuals. We find that neuronal release of potassium and uptake of sodium during stimulation, astrocyte uptake of potassium, sodium, and chloride in passive channels, action of the Na/K/ATPase pump, and osmotically driven transport of water through the astrocyte membrane together seem sufficient for generating ECS shrinkage as such. However, when taking into account ECS and astrocyte ion concentrations observed in connection with neuronal stimulation, the actions of the Na+/K+/Cl− (NKCC1) and the Na+/HCO3− (NBC) cotransporters appear to be critical determinants for achieving observed quantitative levels of ECS shrinkage. Considering the current state of knowledge, the model framework appears sufficiently detailed and constrained to guide future key experiments and pave the way for more comprehensive astroglia–neuron interaction models for normal as well as pathophysiological situations

Test for CCR5 tropism and treatment with maraviroc in Sicily: an observational retrospective multicentre study

Purpose of the study: Maraviroc (MVC) is the first CCR5 inhibitor licensed for clinical use. A pre-treatment test is mandatory to identify R5 tropic patients. Aim of this study is to detect indications and results of tropism test and to evaluate efficacy and tolerability of MVC-based regimen. Methods: An observational retrospective multicentre study was performed in Sicily in 15 Infectious Diseases Units. Clinical records of 213 screened for tropism HIV+ subjects were reviewed for age, sex, risk, clinical stage (CDC, CD4 cell count, HIV RNA viral load), therapeutic line, indication and result of test for tropism; within subjects treated with MVC, HIV RNA, CD4 cell count and metabolic parameters trend and adverse events were analysed. Summary of results: Median age 44 (IQR 30–50) years, 67.1% males; 46.3% heterosexuals, 28.6% MSMs, 21.4% IVDUs; 23.7% CDC A, 32.1% CDC B, 44.2% CDC C; median CD4 was 217 (IQR 121–374) cells/µl and mean of HIV RNA was 4.72 (Cl 95% 4.07–4.67) log10 copies/ml; median therapeutic line was 4 (IQR 2–7). 80.8% were submitted to Trofile™ test, 19.2% to genotypic test, 75.5% after a therapeutic failure. 56.8% of subjects screened were R5, 7.5% X4, 21.6% DM, 14% undefined. All X4 patients were tested after a therapeutic failure; patients screened for toxicity were more frequently R5 (75%) (p<0.01). 76 (35.7%) multi-experienced (at baseline 8% HIV RNA<50 copies/ml, median CD4 cell count 219 (IQR 124–345) cells/µl) subjects were treated with MVC plus an optimized background treatment: MVC was associated in 74% of cases with a protease inhibitors (56% darunavir/ritonavir), in 42% with raltegravir, in 56% with a NUC-sparing regimen. After 12 months of treatment 56.8% (ITT analysis) and 61.7% (AT) of patients had HIV RNA<50 copies/ml; median CD4 cell count was 387 (IQR 222–455) cells/µl. After 24 months 64.8% (ITT) 80% (AT) had HIV-RNA<50 copies/ml. Median CD4 cell count was 381 (IQR 218.515) cells/µl with a median increase of 168 (IQR 54–274) cells/µl. At 24 months median value of total and HDL cholesterol and triglycerides were within the normal range. 7 patients stopped the treatment: 2 died, 1 adverse event, 4 virological failure. Conclusions: Although the test has been proposed to patients with long treatment history and failure, only 3/5 of R5 tropic patients were treated with MVC. An high number of multi-experienced subjects treated with a MVC-based regimen obtained HIV RNA<50 copies/ml and a satisfactory increase of CD4 cell count

Virtual worlds in Australian and New Zealand higher education: Remembering the past, Understanding the present and imagining the future

3D virtual reality, including the current generation of multi-user virtual worlds, has had a long history of use in education and training, and it experienced a surge of renewed interest with the advent of Second Life in 2003. What followed shortly after were several years marked by considerable hype around the use of virtual worlds for teaching, learning and research in higher education. For the moment, uptake of the technology seems to have plateaued, with academics either maintaining the status quo and continuing to use virtual worlds as they have previously done or choosing to opt out altogether. This paper presents a brief review of the use of virtual worlds in the Australian and New Zealand higher education sector in the past and reports on its use in the sector at the present time, based on input from members of the Australian and New Zealand Virtual Worlds Working Group. It then adopts a forward-looking perspective amid the current climate of uncertainty, musing on future directions and offering suggestions for potential new applications in light of recent technological developments and innovations in the area