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Background: Early and severe neuronal loss in the cholinergic basal forebrain is observed in Alzheimer's disease (AD). To date, cholinomimetics play a central role in the symptomatic treatment of AD dementia. Although basic research indicates that a cholinergic deficit is present in AD before dementia, the efficacy of cholinomimetics in mild cognitive impairment (MCI) remains controversial. Predictors of cholinergic impairment could guide individualized therapy.Objective: To investigate if the extent of the cholinergic deficit, measured using positron emission tomography (PET) and the tracer 11C-N-methyl-4-piperidyl acetate (MP4A), could be predicted from the volume of cholinergic basal forebrain nuclei in non-demented AD patients.Methods: Seventeen patients with a high likelihood of MCI due to AD and 18 age-matched cognitively healthy adults underwent MRI-scanning. Basal forebrain volume was assessed using voxel-based morphometry and a cytoarchitectonic atlas of cholinergic nuclei. Cortical acetylcholinesterase (AChE) activity was measured using MP4A-PET.Results: Cortical AChE activity and nucleus basalis of Meynert (Ch4 area) volume were significantly decreased in MCI. The extent of the cholinergic deficit varied considerably across patients. Greater volumes of anterior basal forebrain nuclei (Ch1/2 area) and younger age (Spearman's rho (17)  = -0.596, 95% -CI [-0.905, -0.119] and 0.593, 95% -CI [0.092, 0.863])) were associated with a greater cholinergic deficit.Conclusion: Data suggest that less atrophy of the Ch1/2 area and younger age are associated with a more significant cholinergic deficit in MCI due to AD. Further investigations are warranted to determine if the individual response to cholinomimetics can be inferred from these measures. [ABSTRACT FROM AUTHOR]

Background: The ability for independent bipedal locomotion is an important prerequisite for autonomous mobility and participation in everyday life. Walking requires not only a functional musculoskeletal unit but relies on coordinated activation of muscles and may even require cognitive resources. The time-resolved monitoring of the position of joints, feet, legs and other body segments relative to each other alone or in combination with simultaneous recording of ground reaction forces and concurrent measurement of electrical muscle activity, using surface electromyography, are well-established tools for the objective assessment of gait.Research Question: The Gait Real-time Analysis Interactive Lab (GRAIL) has been introduced for gait analysis in a highly standardized and well-controlled virtual environment. However, apart from high computing capacity and sophisticated software required to run the system, handling of GRAIL data is challenging due to the utilization of different software packages resulting in a huge amount of data stored using different file formats and different sampling rates. These issues make gait analysis even with such a sophisticated instrument rather tedious, especially within the frame of an experimental or clinical study.Methods: A user-friendly Matlab based toolset for automated processing of motion capturing data recorded using the GRAIL, with the inherent option for batch analysis was developed.Results: The toolset allows the reading, resampling, filtering and synchronization of data stored in different input files recorded with the GRAIL. It includes a coordinate-based algorithm for the detection of initial contact and toe-off events to split and normalize data relative to gait cycles. Batch processing of multiple measurements and automatic detection of outliers is possible.Significance: The authors hope that the toolset will be useful to the research community and invite everyone to use, modify or implement it in their own work. [ABSTRACT FROM AUTHOR]

Objective: To determine whether vaginal progesterone for programmed endometrial preparation is noninferior to intramuscular progesterone in terms of live birth rates from frozen embryo transfer (FET).Design: Three-armed, randomized, controlled noninferiority trial.Setting: Multicenter fertility clinic.Patient(s): A total of 1,346 volunteer subjects planning vitrified-warmed transfer of high-quality nonbiopsied blastocysts were screened, of whom 1,125 subjects were ultimately enrolled and randomly assigned to treatment.Intervention(s): The subjects were randomly assigned to receive, in preparation for FET, 50 mg daily of intramuscular progesterone (control group), 200 mg twice daily of vaginal micronized progesterone plus 50 mg of intramuscular progesterone every third day (combination treatment), or 200 mg twice daily of vaginal micronized progesterone.Main Outcome Measure(s): The primary outcome was live birth rate per vitrified-warmed embryo transfer. The secondary outcomes were a positive serum human chorionic gonadotropin test 2 weeks after FET, biochemical pregnancy loss, clinical pregnancy, clinical pregnancy loss, total pregnancy loss, serum luteal progesterone concentration 2 weeks after FET, and patient's experience and attitudes regarding the route of progesterone administration, on the basis of a survey administered to the subjects between FET and pregnancy test.Result(s): A total of 1,060 FETs were completed. The live birth rate was significantly lower in women receiving only vaginal progesterone (27%) than in women receiving intramuscular progesterone (44%) or combination treatment (46%). Fifty percent of pregnancies in women receiving only vaginal progesterone ended in miscarriage.Conclusion(s): The live birth rate after vaginal-only progesterone replacement was significantly reduced, due primarily to an increased rate of miscarriage. Vaginal progesterone supplemented with intramuscular progesterone every third day was noninferior to daily intramuscular progesterone, offering an effective alternative regimen with fewer injections.Clinical Trial Registration Number: NCT02254577. [ABSTRACT FROM AUTHOR]

Introduction: Empirical evidence on Ronald Inglehart's theory of value change shows that subsequent generations show a decline in values of physical and economic security (materialism) in favor of an increase in values of self-expression and autonomy (postmaterialism).Methods: We investigate in a pre-registered study whether Inglehart's theory also applies to partnership, such that millennials think less that they need a partner to be happy. We used data from the German Socio-Economic Panel (SOEP) study on 4540 17-year-olds from 16 birth cohorts.Results: Results show that adolescents' estimated importance of a romantic partner for personal happiness decreases on average with each subsequent birth cohort. Further significant predictors were socialization and relationship status of the parents, birth year of the father, as well as education and sex of the adolescent. Socioeconomic status and education level of the parents and birth year of the mother were not significant.Conclusions: Findings provide initial evidence that as society becomes more individualized, even personal happiness is increasingly seen as independent of significant others. Ronald Inglehart's theory of value change, however, seems to have only limited applicability as an explanatory model for this development. [ABSTRACT FROM AUTHOR]

ASD is a neurodevelopmental disorder impacting 1 in 44 children and early identification of children with ASD is critical for the intervention. Several screening measures have been developed for early identification, including the Autism Spectrum Rating Scales, 6–18 years Parent Report (ASRS). The ASRS has been understudied, and the current study assessed the validity of the ASRS in a clinical sample of 490 children at a tertiary ASD-specialty clinic. Results indicated that the ASRS demonstrated favorable sensitivity, but poor specificity. True positive screening results were more likely to occur for children with a multiracial background, while they were less likely to occur for children with a high social capital. Overall, though the ASRS has clinical utility as a screening measure, it did not perform effectively to differentiate ASD from Non-ASD clinical disorders. [ABSTRACT FROM AUTHOR]

Objectives: Toddler milk (i.e. a nutrient-fortified milk-based drink marketed for children 12-36 months old) is increasingly being marketed in the USA despite not being recommended for young children. There is evidence of targeted toddler milk marketing to Latinos in the USA. This study aimed to explore toddler milk perceptions and behaviours among Latino and non-Latino parents.Design: An online survey assessed toddler milk perceptions, behaviours and interpretations of nutrition-related claims. Multivariable logistic and linear regression explored socio-demographic correlates of parent reported past purchases and perceived healthfulness.Setting: Online.Participants: National convenience sample of 1078 US parents of children aged 2-12 years (48 % Latino).Results: About half of parents (51 %) had previously purchased toddler milk and few (11 %) perceived toddler milk as unhealthy. Latino parents were more likely to have purchased toddler milk than non-Latino parents (P < 0·001), but there were no differences in perceived product healthfulness (P = 0·47). Compared to parents born in the USA, parents living in the USA 10 years or less were more likely to have purchased toddler milk (P < 0·001) and perceive toddler milk as healthier (P = 0·002). Open-ended interpretations of claims were primarily positive, suggesting 'health halo' effects.Conclusions: Common misperceptions about toddler milk healthfulness suggest stronger labelling regulations are needed. Greater reported purchases by Latino parents and recent immigrants warrant further investigation. [ABSTRACT FROM AUTHOR]

Objective: Soft tissue sarcomas (STS) and gastrointestinal stromal tumours (GIST) are a group of rare malignant tumours with a high and heterogenous disease burden. As evidence is scarce, we analysed the prevalence of increased emotional distress and identified distress-associated factors in these patients.Methods: The PROSa-study (Burden and medical care of sarcoma) was conducted between 2017 and 2020 in 39 study centres. Cross-sectional data from adult STS and GIST patients were analysed. Distress was measured with the Patient Health Questionnaire (PHQ-4). The relation of socioeconomic and clinical factors with distress was explored in adjusted logistic regression models.Results: Among 897 patients, 17% reported elevated anxiety and 19% reported depression. Unemployed patients (odds ratio [OR] 6.6; 95% CI 2.9-15.0), and those with a disability pension (OR 3.1; 95% CI 1.9-5.0) were more likely to experience distress compared to employed patients. Also, patients with a disability pass had higher odds of increased distress than those without (OR 1.8; 95% CI 1.2-2.7). Lowest distress was observed in patients 2 to <5 years and ≥5 years after diagnosis (comparison: <6 months) (OR 0.4; 95% CI 0.2-0.6) and (0.3; 95% CI 0.2-0.6). Patients with thoracic STS (vs. lower limbs) had twice the odds to experience distress (OR 2.0; 95% CI 1.1-3.6). Distress was seen almost twice as often in patients with progressive disease (vs. complete remission) (OR 1.7; 95% CI 1.1-2.8).Conclusion: The prevalence of elevated distress in STS and GIST patients is high. In unemployed patients, in those with a disability pension and in newly diagnosed patients a noticeable increase was observed. Clinicians should be aware of these factors and consider the social aspects of the disease. [ABSTRACT FROM AUTHOR]

Objective: The prognosis for ovarian cancer patients remains poor. A key to maximizing survival rates is early detection and treatment. This requires an accurate prediction of malignancy. Our study seeks to improve the accuracy of prediction by focusing on early subjective assessment of malignancy. We therefore investigated the assessment of patients themselves in comparison to the assessment of physicians.Methods: One thousand three hundred and thirty patients participated in a prospective and multicenter study in six hospitals in Berlin. Using univariate analysis and multivariate logistic regression models, we measured the accuracy of the early subjective assessment in comparison to the final histological outcome. Moreover, we investigated factors related to the assessment of patients and physicians.Results: The patients' assessment of malignancy is remarkably accurate. With a positive predictive value of 58%, the majority of patients correctly assessed a pelvic mass as malignant. With more information available, physicians achieved only a slightly more accurate prediction of 63%.Conclusions: For the first time, our study considered subjective factors in the diagnostic process of pelvic masses. This paper demonstrates that the patients' personal assessment should be taken seriously as it can provide a significant contribution to earlier diagnosis and thus improved therapy and overall prognosis. [ABSTRACT FROM AUTHOR]

In chronic myeloid leukemia (CML), combination therapies with tyrosine kinase inhibitors (TKIs) aim to improve the achievement of deep molecular remission that would allow therapy discontinuation. IFN-α is one promising candidate, as it has long-lasting effects on both malignant and immune cells. In connection with a multicenter clinical trial combining dasatinib with IFN-α in 40 patients with chronic-phase CML (NordCML007, NCT01725204), we performed immune monitoring with single-cell RNA and T cell receptor (TCR) sequencing (n = 4, 12 samples), bulk TCRβ sequencing (n = 13, 26 samples), flow cytometry (n = 40, 106 samples), cytokine analyses (n = 17, 80 samples), and ex vivo functional studies (n = 39, 80 samples). Dasatinib drove the immune repertoire toward terminally differentiated NK and CD8+ T cells with dampened functional capabilities. Patients with dasatinib-associated pleural effusions had increased numbers of CD8+ recently activated effector memory T (Temra) cells. In vitro, dasatinib prevented CD3-induced cell death by blocking TCR signaling. The addition of IFN-α reversed the terminally differentiated phenotypes and increased the number of costimulatory intercellular interactions and the number of unique putative epitope-specific TCR clusters. In vitro IFN-α had costimulatory effects on TCR signaling. Our work supports the combination of IFN-α with TKI therapy, as IFN-α broadens the immune repertoire and restores immunological function. [ABSTRACT FROM AUTHOR]