Visual impairment is common in people living with dementia and regular ophthalmological exams may improve their quality of life. We evaluated visual function in a cohort of elderly individuals and ...analyzed its association with their degree of cognitive impairment. Participants underwent neurological and neuropsychological exams, neuro-ophthalmological assessment (visual acuity, intraocular pressure, rates of past ophthalmological pathologies, use of ocular correction, treatments and surgeries) and optical coherence tomography (OCT) scan. We analyzed differences in ophthalmological characteristics among diagnostic groups. The final sample of 1746 study participants aged ≥ 50 comprised 229 individuals with Subjective Cognitive Decline (SCD), 695 with mild cognitive impairment (MCI) and 833 with Dementia (Alzheimer disease: n = 660; vascular dementia: n = 92, Lewy body dementia: n = 34; frontotemporal dementia: n = 19 and other: n = 28). Age, gender and education were used as covariates. Patients with Dementia, compared to those with SCD and MCI, presented worse visual acuity (p < 0.001), used less visual correction (p = 0.02 and p < 0.001, respectively) and fewer ophthalmological treatments (p = 0.004 and p < 0.001, respectively) and underwent fewer ocular surgeries (p = 0.009 and p < 0.001, respectively). OCT image quality worsened in parallel to cognitive decline (Dementia vs SCD: p = 0.008; Dementia vs MCI: p < 0.001). No group differences in past ophthalmological disorders or abnormal OCT findings were detected. Efforts should be made to ensure dementia patients undergo regular ophthalmological assessments to correct their visual function in order to improve their quality of life.
The mitochondrial cytochrome c oxidase, the terminal enzyme of the respiratory chain, contains heme and copper centers for electron transfer. The conserved COX2 subunit contains the CuA site, a ...binuclear copper center. The copper chaperones SCO1, SCO2, and COA6, are required for CuA center formation. Loss of function of these chaperones and the concomitant cytochrome c oxidase deficiency cause severe human disorders. Here we analyzed the molecular function of COA6 and the consequences of COA6 deficiency for mitochondria. Our analyses show that loss of COA6 causes combined complex I and complex IV deficiency and impacts membrane potential-driven protein transport across the inner membrane. We demonstrate that COA6 acts as a thiol-reductase to reduce disulfide bridges of critical cysteine residues in SCO1 and SCO2. Cysteines within the CX3CXNH domain of SCO2 mediate its interaction with COA6 but are dispensable for SCO2–SCO1 interaction. Our analyses define COA6 as thiol-reductase, which is essential for CuA biogenesis.
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•Loss of COA6 affects respiratory chain complexes IV and I.•Decreased membrane potential-driven protein import due to loss of COA6.•Cysteine residues in the CX3CXNH motif of SCO2 mediate COA6 interaction.•COA6 acts as thiol reductase for copper metallochaperones during CuA biogenesis.
The COVID-19 pandemic has brought great disruption to health systems worldwide. This affected ongoing clinical research, particularly among those most vulnerable to the pandemic, like dementia ...patients. Fundació ACE is a research center and memory clinic based in Barcelona, Spain, one of the hardest-hit countries.
To describe the ad-hoc strategic plan developed to cope with this crisis and to share its outcomes.
We describe participants' clinical and demographic features. Additionally, we explain our strategic plan aimed at minimizing the impact on clinical trial research activities, which included SARS-CoV-2 RT-PCR and IgG serological tests to all participants and personnel. The outcomes of the plan are described in terms of observed safety events and drop-outs during the study period.
A total of 130 patients were participating in 16 active clinical trials in Fundació ACE when the lockdown was established. During the confinement, we performed 1018 calls to the participants, which led to identify adverse events in 26 and COVID-19 symptoms in 6. A total of 83 patients (64%) could restart on-site visits as early as May 11, 2020. All SARS-CoV-2 RT-PCR diagnostic tests performed before on-site visits were negative and only three IgG serological tests were positive. Throughout the study period, we only observed one drop-out, due to an adverse event unrelated to COVID-19.
The plan implemented by Fundació ACE was able to preserve safety and integrity of ongoing clinical trials. We must use the lessons learned from the pandemic and design crisis-proof protocols for clinical trials.
Changes in DNA methylation of crucial cancer genes including tumor suppressors can occur early in carcinogenesis, being potentially important early indicators of cancer. The objective of this study ...was to examine a multiplexed approach to assess the methylation of tumor suppressor genes as tumor stratification and clinical outcome prognostic biomarkers for lung cancer.
A multicandidate probe panel interrogated DNA for aberrant methylation status in 18 tumor suppressor genes in lung cancer using a methylation-specific multiplex ligation-dependent probe amplification assay (MS-MLPA). Lung cancer cell lines (n = 7), and primary lung tumors (n = 54) were examined using MS-MLPA.
Genes frequently methylated in lung cancer cell lines including SCGB3A1, ID4, CCND2 were found among the most commonly methylated in the lung tumors analyzed. HLTF, BNIP3, H2AFX, CACNA1G, TGIF, ID4 and CACNA1A were identified as novel tumor suppressor candidates methylated in lung tumors. The most frequently methylated genes in lung tumors were SCGB3A1 and DLC1 (both 50.0%). Methylation rates for ID4, DCL1, BNIP3, H2AFX, CACNA1G and TIMP3 were significantly different between squamous and adenocarcinomas. Methylation of RUNX3, SCGB3A1, SFRP4, and DLC1 was significantly associated with the extent of the disease when comparing localized versus metastatic tumors. Moreover, methylation of HTLF, SFRP5 and TIMP3 were significantly associated with overall survival.
MS-MLPA can be used for classification of certain types of lung tumors and clinical outcome prediction. This latter is clinically relevant by offering an adjunct strategy for the clinical management of lung cancer patients.
Background: We aimed to study anxiety, depression and quality of life in smokers after stroke by sex. Methods: A longitudinal prospective study with a 24-month follow-up of acute stroke patients who ...were previously active smokers. Anxiety and depression were evaluated with the Hospital Anxiety and Depression scale, and quality of life was evaluated with the EQ-5D questionnaire. Results: One hundred and eighty patients participated (79.4% men); their mean age was 57.6 years. Anxiety was most prevalent at 3 months (18.9% in men and 40.5% in women) and depression at 12 months (17.9% in men and 27% in women). The worst perceived health occurred at 24 months (EQ-VAS 67.5 in men and 65.1 in women), which was associated with depression (p < 0.001) and Rankin Scale was worse in men (p < 0.001) and depression in women (p < 0.001). Continued tobacco use was associated with worse perceived health at 3 months in men (p = 0.034) and at 12 months in both sexes. Predictor variables of worse perceived health at 24 months remaining at 3 and 12 months were tobacco use in men and neurological damage in women. Conclusion: Differences by sex are observed in the prevalence of anxiety and depression and associated factors and in the predictive factors of perceived health.
Cognitive biases have been demonstrated to be important in developing and maintaining psychosis. However, self-report measures for everyday clinical practice have been developed only recently. We ...aimed to study one of these instruments for assessing cognitive biases: the Davos Assessment of Cognitive Biases Scale (DACOBS).
In a Spanish sample of 84 patients diagnosed with schizophrenia-spectrum disorders and 152 healthy controls, we examined a) the factor structure using Confirmatory Factor Analysis (CFA) to test the original one-, three- and seven-factor solutions, b) the reliability (Cronbach's alpha), c) the discriminative power (Multivariate Analysis of Covariance - MANCOVA) and d) the relationships of cognitive biases with positive psychotic-like experiences (PPLEs) in healthy individuals and with psychotic symptoms in schizophrenia-spectrum patients.
The CFA revealed that the seven-factor solution achieved the best fit. The DACOBS overall scale (Cronbach's alpha = .92) and subscales obtained good internal consistencies. MANCOVA, controlling for age and education, demonstrated that all subscales differentiated between healthy controls and psychotic patients (Wilks' Lambda = 0.87; F7, 226 = 4.70; p < .000; partial eta squared = 0.13). In addition, the DACOBS showed high correlations with PPLEs (controls) and moderate correlations with positive and general symptoms (patients), demonstrating its predictive validity.
Concluding, the DACOBS proved to be a psychometrically suitable instrument for assessing cognitive biases in psychosis and adequately differentiated between patients and healthy individuals within the Spanish population. Norm scores are provided.
To evaluate the efficacy of plasma rich in growth factors (PRGF) for the treatment of moderate/severe dry eye.
PRGF treatment was administered to 16 patients who had moderate/severe dry eye diagnosed ...and who had not responded previously to other standard treatments. We quantified several growth factors present in the PRGF of each patient and obtained quantitative registers of the symptoms (modified score dry eye questionnaire), both before and after PRGF treatment. We also performed impression cytology to determine the degree of squamous metaplasia before and after PRGF treatment.
PRGF treatment was associated with a statistically significant improvement in score dry eye questionnaire values (P < 0.001). Results from impression cytology corroborated this improvement, but the reduction in the degree of squamous metaplasia was not statistically significant. In 75% of patients treated with PRGF, no further treatments were required, whereas in the remaining 25% other ocular treatments could be reduced.
PRGF led to symptom improvement in patients with moderate/severe dry eye. Surprisingly, the symptoms recorded in the dry eye questionnaire do not always agree with the degree of squamous metaplasia measured by impression cytology.
Subjective cognitive decline (SCD) has been proposed as a potential preclinical stage of Alzheimer's disease (AD). Nevertheless, the genetic and biomarker profiles of SCD individuals remain mostly ...unexplored.
We evaluated apolipoprotein E (APOE) ε4's effect in the risk of presenting SCD, using the Fundacio ACE Healthy Brain Initiative (FACEHBI) SCD cohort and Spanish controls, and performed a meta-analysis addressing the same question. We assessed the relationship between APOE dosage and brain amyloid burden in the FACEHBI SCD and Alzheimer's Disease Neuroimaging Initiative cohorts.
Analysis of the FACEHBI cohort and the meta-analysis demonstrated SCD individuals presented higher allelic frequencies of APOE ε4 with respect to controls. APOE dosage explained 9% (FACEHBI cohort) and 11% (FACEHBI and Alzheimer's Disease Neuroimaging Initiative cohorts) of the variance of cerebral amyloid levels.
The FACEHBI sample presents APOE ε4 enrichment, suggesting that a pool of AD patients is nested in our sample. Cerebral amyloid levels are partially explained by the APOE allele dosage, suggesting that other genetic or epigenetic factors are involved in this AD endophenotype.
•The FACEHBI sample presents APOE ε4 enrichment, suggesting it contains a pool of AD patients.•APOE ε4 is a risk factor of being diagnosed with SCD.•APOE ε4 only explains ≈10% of brain amyloid burden variability in SCD.•The relationship between APOE and brain amyloid burden across clinical diagnoses highlights the importance of adjusting for clinical status when conducting GWAS of cerebral Aβ levels.
Fundació ACE is a non-profit organization providing care based on a holistic model to persons with cognitive disorders and their families for 25 years in Barcelona, Spain. Delivering care to this ...vulnerable population amidst the COVID-19 pandemic has represented a major challenge to our institution.
To share our experience in adapting our model of care to the new situation to ensure continuity of care.
We detail the sequence of events and the actions taken within Fundació ACE to swiftly adapt our face-to-face model of care to one based on telemedicine consultations. We characterize individuals under follow-up by the Memory Unit from 2017 to 2019 and compare the number of weekly visits in 2020 performed before and after the lockdown was imposed.
The total number of individuals being actively followed by Fundació ACE Memory Unit grew from 6,928 in 2017 to 8,147 in 2019. Among those newly diagnosed in 2019, most patients had mild cognitive impairment or mild dementia (42% and 25%, respectively). Weekly visits dropped by 60% following the suspension of face-to-face activity. However, by April 24 we were able to perform 78% of the visits we averaged in the weeks before confinement began.
We have shown that Fundació ACE model of care has been able to successfully adapt to a health and social critical situation as COVID-19 pandemic. Overall, we were able to guarantee the continuity of care while preserving the safety of patients, families, and professionals. We also seized the opportunity to improve our model of care.
Objective
To evaluate the maternal, fetal, and neonatal outcomes of pregnant women complicated with preterm prelabor rupture of membranes (PPROM) eligible for outpatient care.
Methods
This study ...included a retrospective cohort of patients with singleton pregnancies with PPROM between 23+0 to 34+0 weeks who remained pregnant after the first 72 h. Outpatient management was considered in women with clinical, ultrasound and analytical stability, and easy access to hospital. Maternal, fetal, and neonatal results were compared between women managed as inpatients versus those managed as outpatients.
Results
Women eligible for the outpatient management had a better prognostic profile (no anhydramnios, longer cervical length, less intraamniotic infection, and clinical, ultrasound, and analytical stability) and presented a lower gestational age at admission and longer latency to delivery, resulting in a similar gestational age at delivery as the inpatient group. Postpartum curettage, uterine atony, respiratory distress syndrome, and bronchopulmonary dysplasia were less frequent in the outpatient group. Composite maternal‐fetal morbidity and mortality outcomes were similar in both groups, while composite neonatal morbidity and mortality outcomes were significantly lower in the outpatient group.
Conclusion
Outpatient management may be an option for women presenting stable PPROM before 34 weeks when adequate selection criteria are fulfilled. Differences in perinatal outcomes in the outpatient group compared with the inpatient group are probably attributable to baseline characteristics. Further prospective randomized studies are needed to confirm the benefits of outpatient management in PPROM.
Synopsis
Home care may be an option for managing stable preterm prelabor rupture of membranes before 34 weeks when accurate selection criteria are fulfilled.
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