Improvement in clinical markers in CF patients using a reduced glutathione regimen: An uncontrolled, observational study

AbstractCFTR mutation, which causes cystic fibrosis (CF), has also recently been identified as causing glutathione system dysfunction and systemic deficiency of reduced glutathione (GSH). Such dysfunction and deficiency regarding GSH may contribute to the pathophysiology of CF. We followed 13 patients (age range 1–27 years) with cystic fibrosis who were using a regimen of reduced glutathione (GSH), including oral glutathione and inhaled buffered glutathione in an uncontrolled, observational study. Dosage ranged from 66–148 mg/kg/day in divided doses, and the term examined was the initial 5.5 months of GSH use (45 days of incrementally adjusted dose, plus 4 months of use at full dosage). Baseline and post-measurements of FEV1 percent predicted, BMI percentile, and weight percentile were noted, in addition to bacterial status and pulmonary exacerbations. Significant improvement in the following clinical parameters was observed: average improvement in FEV1 percent predicted (N=10) was 5.8 percentage points (p<0.0001), average weight percentile (N=13) increased 8.6 points (p<0.001), BMI percentile (N=11) improved on average 1.22 points (p<0.001). All patients improved in FEV1 and BMI, if measured in their case; 12 of 13 patients improved in weight percentile. Positive sputum cultures of bacteria in 11 patients declined from 13 to 5 (p<0.03) with sputum cultures of Pseudomonas aeruginosa becoming negative in 4 of 5 patients previously culturing PA, including two of three patients chronically infected with PA as determined by antibody status. Use of a daily GSH regimen appears to be associated in CF patients with significant improvement in lung function and weight, and a significant decline in bacteria cultured in this uncontrolled study. These findings bear further clinical investigation in larger, randomized, controlled studies

Intention Attribution and the Development of Moral Evaluation

Research with infants and toddlers suggests that even early in development, humans evaluate others by considering the outcome of an action in relation to the intention underlying it. When someone tries but fails to do a good deed, for example, it seems that it is “the thought that counts.” However, research with slightly older children in the preschool years has produced mixed results: in some cases, children are solely considering the positive or negative outcome of an action when evaluating others, while in others, intention attributions are integrated. Such contradictory findings have prompted debate about the development of moral reasoning. Here, we examine extant research on early moral evaluation and propose that differences in the way that task procedures present intention and outcome information can (1) support or preclude young children’s intention attribution and (2) alter the relative saliency or predominance of each kind of information. In turn, these differences would influence the frequency and degree to which young children generate intention-oriented moral evaluations

The effect of school summer holidays on inequalities in children and young people’s mental health and cognitive ability in the UK using data from the millennium cohort study

BACKGROUND: Summer learning loss has been the subject of longstanding concern among researchers, the public and policy makers. The aim of the current research was to investigate inequality changes in children’s mental health and cognitive ability across the summer holidays. METHODS: We conducted linear and logistic regression analysis of mental health (borderline-abnormal total difficulty and prosocial scores on the strengths and difficulties questionnaire (SDQ)) and verbal cognitive ability (reading, verbal reasoning or vocabulary) at ages 7, 11 and 14, comparing UK Millennium Cohort Study members who were interviewed before and after the school summer holidays. Inequalities were assessed by including interaction terms in the outcome models between a discrete binary variable with values representing time periods and maternal academic qualifications. Coefficients of the interaction terms were interpreted as changes from the pre- to post-holiday period in the extent of inequality in the outcome between participants whose mothers had high or low educational qualifications. Separate models were fitted for each age group and outcome. We used inverse probability weights to allow for differences in the characteristics of cohort members assessed before and after the summer holidays. RESULTS: Mental health (borderline/abnormal SDQ total and prosocial scores) at ages 7 and 14 worsened and verbal cognitive ability scores at age 7 were lower among those surveyed after the summer holidays. Mental health inequalities were larger after the holidays at age 7 ([OR = 1.4; 95%CI (0.6, 3.2) and 14: [OR = 1.5; 95%CI (0.7, 3.2)], but changed little at age 11 (OR = 0.9; 95%CI (0.4, 2.6)]. There were differences in pro-social behaviours among those surveyed before/after the school holidays at age 14 [OR = 1.2; 95%CI (0.5, 3.5)] but not at age 7 or 11. There was little change in inequalities in verbal cognitive ability scores over the school holidays [Age 7: b = 1.3; 95%CI (− 3.3, 6.0); Age 11: b = − 0.7; 95%CI (− 4.3, 2.8); Age 14: b = − 0.3; 95%CI (− 1.0, 0.4)]. CONCLUSION: We found inequalities in mental health and cognitive ability according to maternal education, and some evidence or worsening mental health and mental health inequalities across school summer holidays. We found little evidence of widening inequalities in verbal cognitive ability. Widespread school closures during the COVID-19 restrictions have prompted concerns that prolonged closures may widen health and educational inequalities. Management of school closures should focus on preventing or mitigating inequalities that may arise from differences in the support for mental health and learning provided during closures by schools serving more or less disadvantaged children. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12889-022-12540-2

Reflections on trends in teacher education in Europe using the scenario perspective

SUMMARY In the preceding papers the scenario model of ATEE-RDC19 is used as a reflecting instrument on trends and development in teacher education in different European countries. In this short contribution, a reflection on those papers is made to see whether common trends arise. In this rough picture, it is possible to see that in all analysed countries there is a tendency towards a more pragmatic and individualistic approach in society, influencing teacher education. But these two trends (toward pragmatism and towards idealism) are not in all case studies strongly connected. However, bearing in mind some critical comments on the scenario model, strong and definitive conclusions are to be avoided.info:eu-repo/semantics/publishedVersio

Hormone replacement therapy and false positive recall in the Million Women Study: patterns of use, hormonal constituents and consistency of effect

INTRODUCTION: Current and recent users of hormone replacement therapy (HRT) have an increased risk of being recalled to assessment at mammography without breast cancer being diagnosed ('false positive recall'), but there is limited information on the effects of different patterns of HRT use on this. The aim of this study is to investigate in detail the relationship between patterns of use of HRT and false positive recall. METHODS: A total of 87,967 postmenopausal women aged 50 to 64 years attending routine breast cancer screening at 10 UK National Health Service Breast Screening Units from 1996 to 1998 joined the Million Women Study by completing a questionnaire before screening and were followed for their screening outcome. RESULTS: Overall, 399 (0.5%) participants were diagnosed with breast cancer and 2,629 (3.0%) had false positive recall. Compared to never users of HRT, the adjusted relative risk (95% CI) of false positive recall was: 1.62 (1.43–1.83), 1.80 (1.62–2.01) and 0.76 (0.52–1.10) in current users of oestrogen-only HRT, oestrogen-progestagen HRT and tibolone, respectively (p (heterogeneity) < 0.0001); 1.65 (1.43–1.91), 1.49 (1.22–1.81) and 2.11 (1.45–3.07) for current HRT used orally, transdermally or via an implant, respectively (p (heterogeneity) = 0.2); and 1.84 (1.67–2.04) and 1.75 (1.49–2.06) for sequential and continuous oestrogen-progestagen HRT, respectively (p (heterogeneity) = 0.6). The relative risk of false positive recall among current users appeared to increase with increasing time since menopause, but did not vary significantly according to any other factors examined, including duration of use, hormonal constituents, dose, whether single- or two-view screening was used, or the woman's personal characteristics. CONCLUSION: Current use of oestrogen-only and oestrogen-progestagen HRT, but not tibolone, increases the risk of false positive recall at screening

All clinically-relevant blood components transmit prion disease following a single blood transfusion: a sheep model of vCJD

Variant CJD (vCJD) is an incurable, infectious human disease, likely arising from the consumption of BSE-contaminated meat products. Whilst the epidemic appears to be waning, there is much concern that vCJD infection may be perpetuated in humans by the transfusion of contaminated blood products. Since 2004, several cases of transfusion-associated vCJD transmission have been reported and linked to blood collected from pre-clinically affected donors. Using an animal model in which the disease manifested resembles that of humans affected with vCJD, we examined which blood components used in human medicine are likely to pose the greatest risk of transmitting vCJD via transfusion. We collected two full units of blood from BSE-infected donor animals during the pre-clinical phase of infection. Using methods employed by transfusion services we prepared red cell concentrates, plasma and platelets units (including leucoreduced equivalents). Following transfusion, we showed that all components contain sufficient levels of infectivity to cause disease following only a single transfusion and also that leucoreduction did not prevent disease transmission. These data suggest that all blood components are vectors for prion disease transmission, and highlight the importance of multiple control measures to minimise the risk of human to human transmission of vCJD by blood transfusion

Greedy Elites and Poor Lambs : How Young Europeans Remember the Great War

The present study examines current social representations associated with the origins of the Great War, a major event that has profoundly affected Europe. A survey conducted in 20 European countries (N = 1906 students in social sciences) shows a high consensus: The outbreak of the war is attributed to the warring nations' leaders while the responsibility of the populations is minimized. Building on the concept of social representation of history (Liu & Hilton, 2005), we suggest that the social representations of the Great War fulfill social psychological functions in contemporary Europe. We suggest that WWI may function as a charter for European integration. Their content also suggests a desire to distinguish a positively valued ingroup ("the people") from powerful elites, construed as an outgroup.Peer reviewe

Risk factors for the development of invasive cancer in unresected ductal carcinoma in situ.

BACKGROUND: The natural history of ductal carcinoma in situ (DCIS) remains uncertain. The risk factors for the development of invasive cancer in unresected DCIS are unclear. METHODS: Women diagnosed with DCIS on needle biopsy after 1997 who did not undergo surgical resection for ≥1 year after diagnosis were identified by breast centres and the cancer registry and outcomes were reviewed. RESULTS: Eighty-nine women with DCIS diagnosed 1998-2010 were identified. The median age at diagnosis was 75 (range 44-94) years with median follow-up (diagnosis to death, invasive disease or last review) of 59 (12-180) months. Twenty-nine women (33%) developed invasive breast cancer after a median interval of 45 (12-144) months. 14/29 (48%) with high grade, 10/31 (32%) with intermediate grade and 3/17 (18%) with low grade DCIS developed invasive cancer after median intervals of 38, 60 and 51 months. The cumulative incidence of invasion was significantly higher in high grade DCIS than other grades (p = .0016, log-rank test). Invasion was more frequent in lesions with calcification as the predominant feature (23/50 v. 5/25; p = .042) and in younger women (p = .0002). Endocrine therapy was associated with a lower rate of invasive breast cancer (p = .048). CONCLUSIONS: High cytonuclear grade, mammographic microcalcification, young age and lack of endocrine therapy were risk factors for DCIS progression to invasive cancer. Surgical excision of high grade DCIS remains the treatment of choice. Given the uncertain long-term natural history of non-high grade DCIS, the option of active surveillance of women with this condition should be offered within a clinical trial

Significant benefits of AIP testing and clinical screening in familial isolated and young-onset pituitary tumors

Context Germline mutations in the aryl hydrocarbon receptor-interacting protein (AIP) gene are responsible for a subset of familial isolated pituitary adenoma (FIPA) cases and sporadic pituitary neuroendocrine tumors (PitNETs). Objective To compare prospectively diagnosed AIP mutation-positive (AIPmut) PitNET patients with clinically presenting patients and to compare the clinical characteristics of AIPmut and AIPneg PitNET patients. Design 12-year prospective, observational study. Participants & Setting We studied probands and family members of FIPA kindreds and sporadic patients with disease onset ≤18 years or macroadenomas with onset ≤30 years (n = 1477). This was a collaborative study conducted at referral centers for pituitary diseases. Interventions & Outcome AIP testing and clinical screening for pituitary disease. Comparison of characteristics of prospectively diagnosed (n = 22) vs clinically presenting AIPmut PitNET patients (n = 145), and AIPmut (n = 167) vs AIPneg PitNET patients (n = 1310). Results Prospectively diagnosed AIPmut PitNET patients had smaller lesions with less suprasellar extension or cavernous sinus invasion and required fewer treatments with fewer operations and no radiotherapy compared with clinically presenting cases; there were fewer cases with active disease and hypopituitarism at last follow-up. When comparing AIPmut and AIPneg cases, AIPmut patients were more often males, younger, more often had GH excess, pituitary apoplexy, suprasellar extension, and more patients required multimodal therapy, including radiotherapy. AIPmut patients (n = 136) with GH excess were taller than AIPneg counterparts (n = 650). Conclusions Prospectively diagnosed AIPmut patients show better outcomes than clinically presenting cases, demonstrating the benefits of genetic and clinical screening. AIP-related pituitary disease has a wide spectrum ranging from aggressively growing lesions to stable or indolent disease course