Parental Decision-Making on Childhood Vaccination

A growing number of parents delay vaccinations or are deciding not to vaccinate their children altogether. This increases the risk of contracting vaccine-preventable diseases and disrupting herd immunity, and also impair the trust in the capacities of health care systems to protect people. Vaccine hesitancy is related to a range of both psychological and demographic determinants, such as attitudes towards vaccinations, social norms, and trust in science. We focus on parents and our aim is to understand those determinants, because they are a special group in this issue – proxy decision makers – as they are deciding for their children, who are unable to do so themselves. The fact that deciding to vaccinate is a socially forced choice that concerns a child’s health makes vaccine-related decisions highly important and involving for parents. This high involvement might lead to parents overemphasizing the potential side effects that they know to be vaccine-related, and by amplifying those, parents are more focused on the potential outcomes of vaccine-related decisions, which can yield specific pattern of the outcome bias. We propose two related studies to investigate factors which promote vaccine hesitancy, protective factors that determine parental vaccination decisions, and outcome bias in parental vaccination intentions. We will explore demographic and psychological factors, and test parental involvement related to vaccine hesitancy using an online battery in a correlation panel design study. The second study is an experimental study, in which we will investigate the moderating role of parents’ high involvement in the specific domain of vaccination decision making. We expect that higher involvement among parents, compared to non-parents, will shape the pattern of the proneness to outcome bias. The studies will be conducted across eight countries in Europe and Asia (Finland, Germany, Hong Kong, the Netherlands, Serbia, Slovenia, Spain, and the United Kingdom), rendering findings that will aid with understanding the underlying mechanisms of vaccine hesitancy and paving the way for developing interventions that are custom-made for parents.Peer reviewe

Randomized phase 3 evaluation of trifarotene 50 μg/g cream treatment of moderate facial and truncal acne.

BACKGROUND: Acne vulgaris often affects the face, shoulders, chest, and back, but treatment of nonfacial acne has not been rigorously studied. OBJECTIVES: Assess the safety and efficacy of trifarotene 50 μg/g cream, a novel topical retinoid, in moderate facial and truncal acne. METHODS: Two phase III double-blind, randomized, vehicle-controlled, 12-week studies of once-daily trifarotene cream versus vehicle in subjects aged 9 years or older. The primary end points were rate of success on the face, as determined by the Investigator\u27s Global Assessment (clear or almost clear and ≥2-grade improvement), and absolute change from baseline in inflammatory and noninflammatory counts from baseline to week 12. The secondary end points were rate of success on the trunk (clear or almost clear and ≥2-grade improvement) and absolute change in truncal inflammatory and noninflammatory counts from baseline to week 12. Safety was assessed through adverse events, local tolerability, vital signs, and routine laboratory testing results. RESULTS: In both studies, at week 12 the facial success rates according to the Investigator\u27s Global Assessment and truncal Physician\u27s Global Assessment and change in inflammatory and noninflammatory lesion counts (both absolute and percentage) were all highly significant (P \u3c .001) in favor of trifarotene when compared with the vehicle. LIMITATIONS: Adjunctive topical or systemic treatments were not studied. CONCLUSION: These studies demonstrate that trifarotene appears to be safe, effective, and well tolerated in treatment of both facial and truncal acne

Expropriated from the hereafter: the fate of the landless in the Southern Highlands of Madagascar

During the period following the abolition of slavery by the French colonial government in 1896, the Southern Highlands of Madagascar was settled by ex-slaves. These early settlers constructed a foundation myth of themselves as tompon-tany, or 'masters of the land', a discourse not only equating land with tombs, kinship and ancestors, but also coupled with a skilful deployment of 'Malagasy customs'. In order to exclude later migrants who also wanted to settle, the 'masters of the land' attempted to establish control over holdings in the area. To this end, and to reinforce their own legitimacy as landholders, the tompon-tany labelled subsequent migrants andevo ('lave' or of 'slave descent') who - as a tombless people - have no rights to land. Because they have neither tombs nor ancestors, the landless andevo are socially ostracised and economically marginalised. As an 'impure people', they are not entitled to a place in the hereafter

Hdm2 recruits a hypoxia-sensitive corepressor to negatively regulate p53-dependent transcription

The transcription factor p53 lies at the center of a protein network that controls cell cycle progression and commitment to apoptosis. p53 is inactive in proliferating cells, largely because of negative regulation by the Hdm2/Mdm2 oncoprotein, with which it physically associates. Release from this negative regulation is sufficient to activate p53 and can be triggered in cells by multiple stimuli through diverse pathways. This diversity is achieved in part because Hdm2 uses multiple mechanisms to inactivate p53; it targets p53 for ubiquitination and degradation by the proteosome, shuttles it out of the nucleus and into the cytoplasm, prevents its interaction with transcriptional coactivators, and contains an intrinsic transcriptional repressor activity. Here we show that Hdm2 can also repress p53 activity through the recruitment of a known transcriptional corepressor, hCtBP2. This interaction, and consequent repression of p53-dependent transcription, is relieved under hypoxia or hypoxia-mimicking conditions that are known to increase levels of intracellular NADH. CtBP proteins can undergo an NADH-induced conformational change, which we show here results in a loss of their Hdm2 binding ability. This pathway represents a novel mechanism whereby p53 activity can be induced by cellular stress.<br/

Guidelines for the Neuropsychological Assessment of Patients with Parkinson's Disease

Background Presence of mild cognitive impairment is currently the best predictor for the development of Parkinson's disease dementia. Diagnostic criteria for both Parkinson's with mild cognitive impairment and Parkinson's disease dementia have been suggested by the Movement Disorder Society. However, not all cognitive tests recommended are available in the German language with proper standard values. Objectives To define evidence-based guidelines for neuropsychological assessment of patients with Parkinson's disease in German. Methods Two systematic literature searches were conducted. First, articles that presented international guidelines (consensus papers or reviews) for the application of standardized neuropsychological assessments for the diagnosis of cognitive impairment in Parkinson's disease were selected. Of those, only neuropsychological assessments in German language with normative values referring either to a German, Austrian, or Swiss population were considered. Second, articles comparing test performances of healthy controls vs. Parkinson's disease and/or different cognitive Parkinson's disease subtypes (e.g. no cognitive impairment, Parkinson's with mild cognitive impairment, Parkinson's disease dementia) were selected. Effect sizes for group differentiation were calculated. Results Out of 127 full-text articles reviewed, 48 tests were identified during the first literature search. In the second search, 1716 articles were reviewed and 23 papers selected. The strongest effect sizes for group discrimination were revealed for tests assessing executive function, attention, and visuo-cognitive abilities. Based on the results of the two literature searches, consensus guidelines were defined by the authors, allowing for Level-II diagnosis for Parkinson's with mild cognitive impairment and Parkinson's disease dementia. Conclusions: The presented guidelines may have the potential to standardize and improve the neuropsychological assessment of Parkinson's disease patients in German speaking countries

α-Ketoglutarate Accelerates the Initial Differentiation of Primed Human Pluripotent Stem Cells.

Pluripotent stem cells (PSCs) can self-renew or differentiate from naive or more differentiated, primed, pluripotent states established by specific culture conditions. Increased intracellular α-ketoglutarate (αKG) was shown to favor self-renewal in naive mouse embryonic stem cells (mESCs). The effect of αKG or αKG/succinate levels on differentiation from primed human PSCs (hPSCs) or mouse epiblast stem cells (EpiSCs) remains unknown. We examined primed hPSCs and EpiSCs and show that increased αKG or αKG-to-succinate ratios accelerate, and elevated succinate levels delay, primed PSC differentiation. αKG has been shown to inhibit the mitochondrial ATP synthase and to regulate epigenome-modifying dioxygenase enzymes. Mitochondrial uncoupling did not impede αKG-accelerated primed PSC differentiation. Instead, αKG induced, and succinate impaired, global histone and DNA demethylation in primed PSCs. The data support αKG promotion of self-renewal or differentiation depending on the pluripotent state

Positron emission tomography and functional characterization of a complete ​PBR/​TSPO knockout

The evolutionarily conserved peripheral benzodiazepine receptor (PBR), or 18-kDa translocator protein (TSPO), is thought to be essential for cholesterol transport and steroidogenesis, and thus life. TSPO has been proposed as a biomarker of neuroinflammation and a new drug target in neurological diseases ranging from Alzheimer’s disease to anxiety. Here we show that global C57BL/6-Tspotm1GuWu(GuwiyangWurra)-knockout mice are viable with normal growth, lifespan, cholesterol transport, blood pregnenolone concentration, protoporphyrin IX metabolism, fertility and behaviour. However, while the activation of microglia after neuronal injury appears to be unimpaired, microglia from GuwiyangWurraTSPO knockouts produce significantly less ATP, suggesting reduced metabolic activity. Using the isoquinoline PK11195, the ligand originally used for the pharmacological and structural characterization of the PBR/TSPO, and the imidazopyridines CLINDE and PBR111, we demonstrate the utility of GuwiyangWurraTSPO knockouts to provide robust data on drug specificity and selectivity, both in vitro and in vivo, as well as the mechanism of action of putative TSPO-targeting drugs

Clinical characteristics and outcomes of invasive Lomentospora prolificans infections: Analysis of patients in the FungiScope (R) registry

Objectives Invasive fungal infections caused by Lomentospora prolificans are associated with very high mortality rates and can be challenging to treat given pan-drug resistance to available antifungal agents. The objective of this study was to describe the clinical presentation and outcomes in a cohort of patients with invasive L prolificans infections. Methods We performed a retrospective review of medical records of patients with invasive L prolificans infection in the FungiScope(R) registry of rare invasive fungal infections. Patients diagnosed between 01 January 2008 and 09 September 2019 were included in for analysis. Results The analysis included 41 patients with invasive L prolificans infection from eight different countries. Haematological/oncological malignancies were the most frequent underlying disease (66%), disseminated infection was frequent (61%), and the lung was the most commonly involved organ (44%). Most infections (59%) were breakthrough infections. Progression/deterioration/treatment failure was observed in 23/40 (58%) of patients receiving antifungal therapy. In total, 21/41 (51%) patients, and 77% of patients with underlying haematological/oncological malignancy, had a fatal outcome attributed to invasive fungal infection. Combination antifungal therapy was frequent (24/40) and associated with improved survival. In particular, treatment regimens including terbinafine were significantly associated with higher treatment success at final assessment (P = .012), with a positive trend observed for treatment regimens that included voriconazole (P = .054). Conclusions Lomentospora prolificans infections were associated with mortality rates of 77% and above in patients with underlying haematological/oncological malignancies and those with disseminated infections. While combination therapy is the preferred option for now, the hope lies with novel antifungals currently under development

Subtypes of mild cognitive impairment in patients with Parkinson's disease: evidence from the LANDSCAPE study

Objective Inconsistent results exist regarding the cognitive profile in patients with Parkinson's disease with mild cognitive impairment (PD-MCI). We aimed at providing data on this topic from a large cohort of patients with PD-MCI. Methods Sociodemographic, clinical and neuropsychological baseline data from patients with PD-MCI recruited in the multicentre, prospective, observational DEMPARK/LANDSCAPE study were analysed. Results 269 patients with PD-MCI (age 67.8 +/- 7.4, Unified Parkinson's Disease Rating Scale (UPDRS-III) scores 23.2 +/- 11.6) were included. PD-MCI subtypes were 39.4% non-amnestic single domain, 30.5% amnestic multiple domain, 23.4% non-amnestic multiple domain and 6.7% amnestic single domain. Executive functions were most frequently impaired. The most sensitive tests to detect cognitive dysfunctions were the Modified Card Sorting Test, digit span backwards and word list learning direct recall. Multiple stepwise regression analyses showed that global cognition, gender and age, but not education or disease-related parameters predicted PD-MCI subtypes. Conclusions This study with the so far largest number of prospectively recruited patients with PD-MCI indicates that non-amnestic PD-MCI is more frequent than amnestic PD-MCI; executive dysfunctions are the most typical cognitive symptom in PD-MCI; and age, gender and global cognition predict the PD-MCI subtype. Longitudinal data are needed to test the hypothesis that patients with PD-MCI with specific cognitive profiles have different risks to develop dementia