Validation of the short forms of the Pelvic Floor Distress Inventory (PFDI-20), Pelvic Floor Impact Questionnaire (PFIQ-7), and Pelvic Organ Prolapse/ Urinary Incontinence Sexual Questionnaire (PISQ-12) in Finnish

Background: Although several validated generic health-related quality of life instruments exist, disease-specific instruments are important as they are often more sensitive to changes in symptom severity. It is essential to validate the instruments in a new population and language before their use. The objective of the study was to translate into Finnish the short forms of three condition-specific questionnaires (PFDI-20, PFIQ-7 and PISQ-12) and to evaluate their psychometric properties in Finnish women with symptomatic pelvic organ prolapse.Methods: A multistep translation method was used followed by an evaluation of validity and reliability in prolapse patients. Convergent and discriminant validity, internal consistency and reliability via test-retest were calculated.Results: Sixty-three patients waiting for prolapse surgery filled the three questionnaires within two weeks. Response rate for each item was high in PFDI-20 and PISQ-12 (99.8 and 98.9% respectively). For PFIQ-7 response rate was only 60%. In PFIQ-7, six respondents (9.5%) reached the minimum value of zero showing floor effect. None of the instruments had ceiling effect. Based on the item-total correlations both PFIQ-7 and PFDI-20 had acceptable convergent validity, while the convergent validity of PISQ-12 was lower, r = 0.138-0.711. However, in this instrument only three questions (questions 6, 10 and 11) had r < 0.3 while others had r = 0.380. In the test-retest analysis all the three instruments showed good reliability (ICC 0.75-0.92). Similarly, the internal consistency of the instruments, measured by Cronbach's a, was good (range 0.69-0.96) indicating high homogeneity.Conclusions: Finnish validated translation of the PFDI-20 and PISQ-12 have acceptable psychometric properties and can be used for both research purposes and clinical evaluation of pelvic organ prolapse symptoms. The Finnish version of PFIQ-7 displayed low response rate and some evidence of a floor effect, and thus its use is not recommended in its current form

Plasma phosphorylated tau 217 and phosphorylated tau 181 as biomarkers in Alzheimer's disease and frontotemporal lobar degeneration: a retrospective diagnostic performance study

Background: Plasma tau phosphorylated at threonine 217 (p-tau217) and plasma tau phosphorylated at threonine 181 (p-tau181) are associated with Alzheimer's disease tau pathology. We compared the diagnostic value of both biomarkers in cognitively unimpaired participants and patients with a clinical diagnosis of mild cognitive impairment, Alzheimer's disease syndromes, or frontotemporal lobar degeneration (FTLD) syndromes. / Methods: In this retrospective multicohort diagnostic performance study, we analysed plasma samples, obtained from patients aged 18–99 years old who had been diagnosed with Alzheimer's disease syndromes (Alzheimer's disease dementia, logopenic variant primary progressive aphasia, or posterior cortical atrophy), FTLD syndromes (corticobasal syndrome, progressive supranuclear palsy, behavioural variant frontotemporal dementia, non-fluent variant primary progressive aphasia, or semantic variant primary progressive aphasia), or mild cognitive impairment; the participants were from the University of California San Francisco (UCSF) Memory and Aging Center, San Francisco, CA, USA, and the Advancing Research and Treatment for Frontotemporal Lobar Degeneration Consortium (ARTFL; 17 sites in the USA and two in Canada). Participants from both cohorts were carefully characterised, including assessments of CSF p-tau181, amyloid-PET or tau-PET (or both), and clinical and cognitive evaluations. Plasma p-tau181 and p-tau217 were measured using electrochemiluminescence-based assays, which differed only in the biotinylated antibody epitope specificity. Receiver operating characteristic analyses were used to determine diagnostic accuracy of both plasma markers using clinical diagnosis, neuropathological findings, and amyloid-PET and tau-PET measures as gold standards. Difference between two area under the curve (AUC) analyses were tested with the Delong test. / Findings: Data were collected from 593 participants (443 from UCSF and 150 from ARTFL, mean age 64 years [SD 13], 294 [50%] women) between July 1 and Nov 30, 2020. Plasma p-tau217 and p-tau181 were correlated (r=0·90, p<0·0001). Both p-tau217 and p-tau181 concentrations were increased in people with Alzheimer's disease syndromes (n=75, mean age 65 years [SD 10]) relative to cognitively unimpaired controls (n=118, mean age 61 years [SD 18]; AUC=0·98 [95% CI 0·95–1·00] for p-tau217, AUC=0·97 [0·94–0·99] for p-tau181; pdiff=0·31) and in pathology-confirmed Alzheimer's disease (n=15, mean age 73 years [SD 12]) versus pathologically confirmed FTLD (n=68, mean age 67 years [SD 8]; AUC=0·96 [0·92–1·00] for p-tau217, AUC=0·91 [0·82–1·00] for p-tau181; pdiff=0·22). P-tau217 outperformed p-tau181 in differentiating patients with Alzheimer's disease syndromes (n=75) from those with FTLD syndromes (n=274, mean age 67 years [SD 9]; AUC=0·93 [0·91–0·96] for p-tau217, AUC=0·91 [0·88–0·94] for p-tau181; pdiff=0·01). P-tau217 was a stronger indicator of amyloid-PET positivity (n=146, AUC=0·91 [0·88–0·94]) than was p-tau181 (n=214, AUC=0·89 [0·86–0·93]; pdiff=0·049). Tau-PET binding in the temporal cortex was more strongly associated with p-tau217 than p-tau181 (r=0·80 vs r=0·72; pdiff<0·0001, n=230). / Interpretation: Both p-tau217 and p-tau181 had excellent diagnostic performance for differentiating patients with Alzheimer's disease syndromes from other neurodegenerative disorders. There was some evidence in favour of p-tau217 compared with p-tau181 for differential diagnosis of Alzheimer's disease syndromes versus FTLD syndromes, as an indication of amyloid-PET-positivity, and for stronger correlations with tau-PET signal. Pending replication in independent, diverse, and older cohorts, plasma p-tau217 and p-tau181 could be useful screening tools to identify individuals with underlying amyloid and Alzheimer's disease tau pathology. / Funding: US National Institutes of Health, State of California Department of Health Services, Rainwater Charitable Foundation, Michael J Fox foundation, Association for Frontotemporal Degeneration, Alzheimer's Association

The enigma of in vivo oxidative stress assessment: isoprostanes as an emerging target

Oxidative stress is believed to be one of the major factors behind several acute and chronic diseases, and may also be associated with ageing. Excess formation of free radicals in miscellaneous body environment may originate from endogenous response to cell injury, but also from exposure to a number of exogenous toxins. When the antioxidant defence system is overwhelmed, this leads to cell damage. However, the measurement of free radicals or their endproducts is tricky, since these compounds are reactive and short lived, and have diverse characteristics. Specific evidence for the involvement of free radicals in pathological situations has been difficult to obtain, partly owing to shortcomings in earlier described methods for the measurement of oxidative stress. Isoprostanes, which are prostaglandin-like bioactive compounds synthesized in vivo from oxidation of arachidonic acid, independently of cyclooxygenases, are involved in many human diseases, and their measurement therefore offers a way to assess oxidative stress. Elevated levels of F2-isoprostanes have also been seen in the normal human pregnancy, but their physiological role has not yet been defined. Large amounts of bioactive F2-isoprostanes are excreted in the urine in normal basal situations, with a wide interindividual variation. Their exact role in the regulation of normal physiological functions, however, needs to be explored further. Current understanding suggests that measurement of F2-isoprostanes in body fluids provides a reliable analytical tool to study oxidative stress-related diseases and experimental inflammatory conditions, and also in the evaluation of various dietary antioxidants, as well as drugs with radical-scavenging properties. However, assessment of isoprostanes in plasma or urine does not necessarily reflect any specific tissue damage, nor does it provide information on the oxidation of lipids other than arachidonic acid

The Electroencephalogram as a Biomarker Based on Signal Processing Using Nonlinear Techniques to Detect Dementia

Dementia being a syndrome caused by a brain disease of a chronic or progressive nature, in which the irreversible loss of intellectual abilities, learning, expressions arises; including memory, thinking, orientation, understanding and adequate communication, of organizing daily life and of leading a family, work and autonomous social life; leads to a state of total dependence; therefore, its early detection and classification is of vital importance in order to serve as clinical support for physicians in the personalization of treatment programs. The use of the electroencephalogram as a tool for obtaining information on the detection of changes in brain activities. This article reviews the types of cognitive spectrum dementia, biomarkers for the detection of dementia, analysis of mental states based on electromagnetic oscillations, signal processing given by the electroencephalogram, review of processing techniques, results obtained where it is proposed the mathematical model about neural networks, discussion and finally the conclusions

Exploring the Impact of the Therapeutic Alliance and Structural Factors in Treatment Groups for Domestically Abusive Men

This research explored domestic abuse perpetrator group dynamics with especial attention to the vital role ofthe therapeutic alliance and the constructions men have of their own narratives; it provides important lessons. for future efficacy research with its attention to group process rather than a focus on measurable outcomes. Three Programmes participated and differed from each other on characteristics such as duration and approach; one was mainly therapeutic with additional cognitive-behavioural aspects (Programme A), one was mainly cognitive-behavioural with additional therapeutic aspects (Programme B), and one was the Home Office accredited Integrated Domestic Abuse Programme (IDAP) (cognitive-behavioural only) (Programme C). The data set was comprised of interviews with men from each programme (completers and non-completers, n=20), 50 hours of reviewed sessions from each Programme, and a Staff Day. The method of analysis for the interview data was based on the psychoanalytic defended subject, Free Association Narrative Analysis. RESULTS Key findings from this research are: that there were therapeutic alliances in the group between the facilitators and the participants and in one instance between participants; that even a strong alliance needed sufficient time to be of greater benefit to the participant; and that negative and neutral alliances generally appeared unsupportive of treatment goals. Facilitation and structural factors facilitating a robust alliance were: attention to feelings, leavings and loss; consistently high quality facilitation; boundaried compassion; gender equality; group alliance; appropriate facilitator sharing; organisational clarity; motivational interviewing; individual session work; longer length and content flexibility. Factors found to undermine the alliance were: inconsistent facilitation; disrespectful communication; inattention to feelings, loss and leavings; pedagogy; shaming; content rigidity and lack of organisational clarity. The term 'boundaried compassion' was developed to bridge the necessity to label some behaviours as unacceptable whilst being compassionate to the person. Additional findings: the high quality facilitation in the context ofa brief intervention (15 weeks for Programme B) was experienced as genuinely traumatic for most of their respondents. Combining CBT and other therapeutical approaches appears complimentary. When men were committed to the process of change, they fell into two categories: putting a 'leash' on (controlling) their anger, and 'breaking down the mask' of their defences (changing fundamental attitudes and beliefs, including those regarding masculinity).EThOS - Electronic Theses Online ServiceGBUnited Kingdo

Discriminative Accuracy of Plasma Phospho-tau217 for Alzheimer Disease vs Other Neurodegenerative Disorders

IMPORTANCE:There are limitations in current diagnostic testing approaches for Alzheimer disease (AD). OBJECTIVE: To examine plasma tau phosphorylated at threonine 217 (P-tau217) as a diagnostic biomarker for AD. DESIGN, SETTING, AND PARTICIPANTS: Three cross-sectional cohorts: an Arizona-based neuropathology cohort (cohort 1), including 34 participants with AD and 47 without AD (dates of enrollment, May 2007-January 2019); the Swedish BioFINDER-2 cohort (cohort 2), including cognitively unimpaired participants (n = 301) and clinically diagnosed patients with mild cognitive impairment (MCI) (n = 178), AD dementia (n = 121), and other neurodegenerative diseases (n = 99) (April 2017-September 2019); and a Colombian autosomal-dominant AD kindred (cohort 3), including 365 PSEN1 E280A mutation carriers and 257 mutation noncarriers (December 2013-February 2017). EXPOSURES: Plasma P-tau217. MAIN OUTCOMES AND MEASURES: Primary outcome was the discriminative accuracy of plasma P-tau217 for AD (clinical or neuropathological diagnosis). Secondary outcome was the association with tau pathology (determined using neuropathology or positron emission tomography [PET]). RESULTS: Mean age was 83.5 (SD, 8.5) years in cohort 1, 69.1 (SD, 10.3) years in cohort 2, and 35.8 (SD, 10.7) years in cohort 3; 38% were women in cohort 1, 51% in cohort 2, and 57% in cohort 3. In cohort 1, antemortem plasma P-tau217 differentiated neuropathologically defined AD from non-AD (area under the curve [AUC], 0.89 [95% CI, 0.81-0.97]) with significantly higher accuracy than plasma P-tau181 and neurofilament light chain (NfL) (AUC range, 0.50-0.72; P  .15). In cohort 3, plasma P-tau217 levels were significantly greater among PSEN1 mutation carriers, compared with noncarriers, from approximately 25 years and older, which is 20 years prior to estimated onset of MCI among mutation carriers. Plasma P-tau217 levels correlated with tau tangles in participants with (Spearman ρ = 0.64; P < .001), but not without (Spearman ρ = 0.15; P = .33), β-amyloid plaques in cohort 1. In cohort 2, plasma P-tau217 discriminated abnormal vs normal tau-PET scans (AUC, 0.93 [95% CI, 0.91-0.96]) with significantly higher accuracy than plasma P-tau181, plasma NfL, CSF P-tau181, CSF Aβ42:Aβ40 ratio, and MRI measures (AUC range, 0.67-0.90; P < .05), but its performance was not significantly different compared with CSF P-tau217 (AUC, 0.96; P = .22). CONCLUSIONS AND RELEVANCE: Among 1402 participants from 3 selected cohorts, plasma P-tau217 discriminated AD from other neurodegenerative diseases, with significantly higher accuracy than established plasma- and MRI-based biomarkers, and its performance was not significantly different from key CSF- or PET-based measures. Further research is needed to optimize the assay, validate the findings in unselected and diverse populations, and determine its potential role in clinical care