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Background: The World Health Organization (WHO) has developed the Integrated Care for Older People (ICOPE) strategy to face the challenges of ageing societies. This strategy is focused on person centered care and the assessment intrinsic capacity (IC). Early identification of five domains of IC (cognition, locomotion, vitality, sensory (hearing and vision), and psychological) has been shown to be related with adverse outcomes and can guide actions towards primary prevention and healthy ageing. IC assessment proposed by the WHO ICOPE guidelines is composed by two steps: First, Screening for decreased IC by the ICOPE Screening tool; second, by the reference standard methods. The aim was to assess the performance of diagnostic measures (sensibility, specificity, diagnostic accuracy, and agreement of the ICOPE Screening tool) compared to the reference standard methods in European community-dwelling older adults., Methods: Cross-sectional analysis of the baseline of the ongoing VIMCI (Validity of an Instrument to Measure Intrinsic Capacity) cohort study, which was carried out in Primary Care centers and outpatient clinics from 5 rural and urban territories in Catalonia (Spain). Participants were 207community dwelling persons ≥ 70-year-old with Barthel ≥ 90, without dementia or advanced chronic conditions who provided their consent to participate. The 5 IC domains were assessed by the ICOPE Screening tool and the reference methods (SPPB, gait speed, MNA, Snellen chart, audiometry, MMSE, GDS5) during patients' visit. Agreement was assessed with the Gwet AC1 index., Results: ICOPE Screening tool sensitivity was higher for cognition (0.889) and ranged between 0.438 and 0.569 for most domains. Specificity ranged from 0.682 to 0.96, diagnostic accuracy from 0.627 to 0.879, Youden index from 0.12 to 0.619, and Gwet AC1 from 0.275 to 0.842., Conclusion: The ICOPE screening tool showed fair performance of diagnostic measures; it was helpful to identify those participants with satisfactory IC and showed a modest ability to identify decreased IC in older people with high degree of autonomy. Since low sensitivities were found, a process of external validation would be recommended to reach better discrimination. Further studies about the ICOPE Screening tool and its performance of diagnostic measures in different populations are urgently required., (© 2023. The Author(s).)

The RNA-binding protein RBFOX1 is an important regulator of neuron development and neuronal excitability. Rbfox1 is a dosage-sensitive gene and in both mice and humans, decreased expression of Rbfox1 has been linked to neurodevelopmental disorders. Alternative promoters drive expression of Rbfox1 transcript isoforms that encode an identical protein. The tissue- and developmental stage-specific expression of these isoforms, as well as the underlying regulatory mechanisms, are, however, unclear. Here, we set out to capture all of the Rbfox1 transcript isoforms and identify transcriptional mechanisms that regulate brain-specific Rbfox1 expression. Isoform sequencing identified multiple alternative Rbfox1 transcript variants in the mouse cerebral cortex, including transcripts with novel first exons, alternatively spliced exons and 3'-truncations. Quantitative RT-PCR determined the expression of the alternative first exons in the developing cerebral cortex and different subregions of the juvenile brain. Alternative first exons were found to be highly stage- and subregion specific in their expression patterns suggesting that they fulfill specific functions during cortex development and in different brain regions. Using reporter assays we found that the promoter regions of the two first exons E1B and E1C/E1C.1 contain several functional E-boxes. Together, we provide an extensive picture of Rbfox1 isoform expression. We further identified important regulatory mechanisms that drive neuron-specific Rbfox1 expression. Thus, our study forms the basis for further research into the mechanisms that ensure physiological Rbfox1 expression in the brain. It also helps to understand why, in patients with neurodevelopmental disorders deletion of individual RBFOX1 transcript isoforms could affect brain function., (Copyright © 2020 Casanovas, Schlichtholz, Mühlbauer, Dewi, Schüle, Strand, Strand, Zografidou and Winter.)

Background: Biomarkers for metastatic castration-resistant prostatic cancer (mCRPC) are an unmet medical need., Methods: The prognostic and predictive value for survival and response to salvage hormonal therapy (SHT) of baseline testosterone level (TL) was analysed in a cohort of 101 mCRPC patients participating in 9 non-hormonal first-line chemotherapy phase II-III trials. Inclusion criteria in all trials required a TL of <50 ng dl(-1)., Results: Median age: 70 years; visceral metastases: 19.8%; median prostate-specific antigen (PSA): 50.7 ng ml(-1); median TL: 11.5 ng dl(-1). Median overall survival (OS; 24.5 months) was significantly longer if baseline TL was above (High TL; n=52) than under (Low TL; n=49) the TL median value (32.7 vs 22.4 months, respectively; P=0.0162, hazard ratio (HR)=0.6). The presence of anaemia was an unfavourable prognostic factor (median OS: 20.6 vs 28.4 months; P=0.0025, HR=1.88 (CI95%: 1.01-3.48)). Patients presenting both anaemia and low testosterone had a worse outcome compared to those with one or none of them (median OS: 17.9 vs 22.4 vs 38.1 months; P=0.0024). High vs Low TL was associated with PSA response rate (55.6% vs 21.7%) in 41 patients receiving SHT., Conclusion: Testosterone level under castration range was a prognostic factor for survival mCRPC patients. The PSA response to SHT differed depending on TLs. Testosterone levels might help in treatment decision.

Background: Hepatitis C virus (HCV) genotyping is mandatory for tailoring dose and duration of pegylated interferon-α plus ribavirin treatment and for deciding on triple therapy eligibility. Additionally, subtyping may play a role in helping to select future treatment regimens that include directly-acting antivirals. However, commercial assays for HCV genotyping fail to identify the genotype/subtype in some cases., Objective: Our aims were (i) to determine the success rate of the commercial genotyping assay Abbott RealTime HCV Genotype II at identifying the genotype and the HCV-1 subtype; and (ii) to phylogenetically characterise the obtained indeterminate results., Study Design: HCV genotyping results obtained between 2009 and 2012 in a Spanish reference hospital were reviewed. A total of 896 people were genotyped with the Abbott RealTime HCV Genotype II assay. Specimens with an indeterminate result were retrospectively genotyped using the reference method based on the phylogenetic analysis of HCV NS5B sequences., Results: Using the commercially available assay, an indeterminate HCV genotype result was obtained in 20 of 896 patients (2.2%); these corresponded to genotypes 3a, 3k and 4d. Importantly, 8.6% of all cases where genotype 3 was detected were indeterminate. In addition, the HCV-1 subtype was not assigned in 29 of 533 cases (5.4%)., Conclusions: The implementation in the clinical microbiology laboratory of the reference method for HCV genotyping allows indeterminate genotype/subtype results to be interpreted and may lead to the identification of previously uncharacterised subtypes., (Copyright © 2013 Elsevier B.V. All rights reserved.)

Background: Only about 50% of patients chronically infected with HCV genotype 1 (HCV-1) respond to treatment with pegylated interferon-alfa and ribavirin (dual therapy), and protease inhibitors have to be administered together with these drugs increasing costs and side-effects. We aimed to develop a predictive model of treatment response based on a combination of baseline clinical and viral parameters., Methodology: Seventy-four patients chronically infected with HCV-1b and treated with dual therapy were studied (53 retrospectively -training group-, and 21 prospectively -validation group-). Host and viral-related factors (viral load, and genetic variability in the E1-E2, core and Interferon Sensitivity Determining Region) were assessed. Multivariate discriminant analysis and decision tree analysis were used to develop predictive models on the training group, which were then validated in the validation group., Principal Findings: A multivariate discriminant predictive model was generated including the following variables in decreasing order of significance: the number of viral variants in the E1-E2 region, an amino acid substitution pattern in the viral core region, the IL28B polymorphism, serum GGT and ALT levels, and viral load. Using this model treatment outcome was accurately predicted in the training group (AUROC = 0.9444; 96.3% specificity, 94.7% PPV, 75% sensitivity, 81% NPV), and the accuracy remained high in the validation group (AUROC = 0.8148, 88.9% specificity, 90.0% PPV, 75.0% sensitivity, 72.7% NPV). A second model was obtained by a decision tree analysis and showed a similarly high accuracy in the training group but a worse reproducibility in the validation group (AUROC = 0.9072 vs. 0.7361, respectively)., Conclusions and Significance: The baseline predictive models obtained including both host and viral variables had a high positive predictive value in our population of Spanish HCV-1b treatment naïve patients. Accurately identifying those patients that would respond to the dual therapy could help reducing implementation costs and additional side effects of new treatment regimens.

Introduction: The association between difficulties on motor skills, visual-hand coordination and excess motor activity was described previously of being established the attention-deficit/hyperactivity disorder (ADHD) as a diagnostic category. These disorders have been grouped under different terminologies, being one of them the soft neurological signs (SNS). Traditionally, the European scientific community has put more attention on the SNS than the American one. However, nowadays there are a lot of neuropediatrician and community pediatrician that continue to think that those deficits, together with inattention and hyperactivity, form part of the same disorder., Development: In this article we have tried to do a neurobiological revision of the movement and the possible relationship between motor problems and cognitive processes from different points of view: neuroanatomical, findings on different clinical examination tests and neuropsychological experimental models., Conclusion: Most of the revised articles conclude that the SNS prevalence is greater in ADHD children compared with control. Therefore we recommend to include the SNS in the evaluation and diagnosis protocols of these disorders in order to improve the sensitivity and specificity of the diagnosis and to be able to evaluate the real needs of the ADHD patients.

There is a large population of Turkish-speaking migrants living in London, many of whom are refugees (Enneli, Modood, & Bradley, 2005). Primary care and secondary mental health services have consistently reported poor continuity of care among patients from this community. The aim of this study was to explore the possible interconnection of causal attributions and pathways into care among Turkish-speaking, mainly Kurdish, patients with a past history of psychosis. Narratives of illness were elicited from informants. Physical symptomatology was a prominent feature of presentation in this group. These patients did not discuss their health problems conceptualized as uniform ;models' of illness, but rather in an attributional style that emphasized the experience of traumatic life events, often related to the overarching problem of exile and settlement. Childhood and family issues of poverty and domestic violence were often raised by patients, but tended to be backgrounded as having little contributory significance. These patients sought intervention, serially or in combination, from a diverse range of practitioners, including private healthcare and traditional healers or hocas. Their explanatory models of illness were complex and fragmentary and the relationship between explanations and help seeking is seldom linear. The implications of these findings for health services are discussed.

The lichen Ramalina ecklonii (Spreng.) Mey. and Flot. was transplanted to 29 biomonitoring sites in the southeastern area of Córdoba, Argentina and tested for chlorophyll a, phaeophytin a, conjugated dienes concentration, malondialdehyde, soluble protein content and sulfur accumulation. The biomonitoring sites were determined according to (i) vehicular traffic levels, and (ii) industrial density, i.e. number and type of industries (small and medium) close to each of the sites. Each of the two groups were then broken down into three categories which provided a basis for performance analysis and quantification of the chemical parameters in the biomonitor. A pollution index (P.I.) was calculated based on the ratio of phaeophytin a to chlorophyll a and ratio of sulfur, malonaldehyde and conjugated dienes in transplanted specimens to sulfur, malonaldehyde and conjugated dienes in the freshly picked specimens. Significant differences were observed in sulfur content and P.I. in lichen samples that had been transplanted to sites with different vehicular traffic levels. At the same time, significant differences in the phaeophytin a concentration, phaeophytin a/chlorophyll a ratio and P.I. were observed at sites characterized by different levels of industrial density (all with low-to-medium traffic).