Frontotemporal dementia presentation in patients with heterozygous p.H157Y variant of TREM2.

BACKGROUND: The triggering receptor expressed on myeloid cell 2 (TREM2) is a major regulator of neuroinflammatory processes in neurodegeneration. To date, the p.H157Y variant of TREM2 has been reported only in patients with Alzheimer's disease. Here, we report three patients with frontotemporal dementia (FTD) from three unrelated families with heterozygous p.H157Y variant of TREM2: two patients from Colombian families (study 1) and a third Mexican origin case from the USA (study 2). METHODS: To determine if the p.H157Y variant might be associated with a specific FTD presentation, we compared in each study the cases with age-matched, sex-matched and education-matched groups-a healthy control group (HC) and a group with FTD with neither TREM2 mutations nor family antecedents (Ng-FTD and Ng-FTD-MND). RESULTS: The two Colombian cases presented with early behavioural changes, greater impairments in general cognition and executive function compared with both HC and Ng-FTD groups. These patients also exhibited brain atrophy in areas characteristic of FTD. Furthermore, TREM2 cases showed increased atrophy compared with Ng-FTD in frontal, temporal, parietal, precuneus, basal ganglia, parahippocampal/hippocampal and cerebellar regions. The Mexican case presented with FTD and motor neuron disease (MND), showing grey matter reduction in basal ganglia and thalamus, and extensive TDP-43 type B pathology. CONCLUSION: In all TREM2 cases, multiple atrophy peaks overlapped with the maximum peaks of TREM2 gene expression in crucial brain regions including frontal, temporal, thalamic and basal ganglia areas. These results provide the first report of an FTD presentation potentially associated with the p.H157Y variant with exacerbated neurocognitive impairments.

Multivariate word properties in fluency tasks reveal markers of Alzheimer's dementia.

INTRODUCTION: Verbal fluency tasks are common in Alzheimer's disease (AD) assessments. Yet, standard valid response counts fail to reveal disease-specific semantic memory patterns. Here, we leveraged automated word-property analysis to capture neurocognitive markers of AD vis-à-vis behavioral variant frontotemporal dementia (bvFTD). METHODS: Patients and healthy controls completed two fluency tasks. We counted valid responses and computed each word's frequency, granularity, neighborhood, length, familiarity, and imageability. These features were used for group-level discrimination, patient-level identification, and correlations with executive and neural (magnetic resonanance imaging [MRI], functional MRI [fMRI], electroencephalography [EEG]) patterns. RESULTS: Valid responses revealed deficits in both disorders. Conversely, frequency, granularity, and neighborhood yielded robust group- and subject-level discrimination only in AD, also predicting executive outcomes. Disease-specific cortical thickness patterns were predicted by frequency in both disorders. Default-mode and salience network hypoconnectivity, and EEG beta hypoconnectivity, were predicted by frequency and granularity only in AD. DISCUSSION: Word-property analysis of fluency can boost AD characterization and diagnosis. HIGHLIGHTS: We report novel word-property analyses of verbal fluency in AD and bvFTD. Standard valid response counts captured deficits and brain patterns in both groups. Specific word properties (e.g., frequency, granularity) were altered only in AD. Such properties predicted cognitive and neural (MRI, fMRI, EEG) patterns in AD. Word-property analysis of fluency can boost AD characterization and diagnosis.

Educational disparities in brain health and dementia across Latin America and the United States.

BACKGROUND: Education influences brain health and dementia. However, its impact across regions, specifically Latin America (LA) and the United States (US), is unknown. METHODS: A total of 1412 participants comprising controls, patients with Alzheimer's disease (AD), and frontotemporal lobar degeneration (FTLD) from LA and the US were included. We studied the association of education with brain volume and functional connectivity while controlling for imaging quality and variability, age, sex, total intracranial volume (TIV), and recording type. RESULTS: Education influenced brain measures, explaining 24%-98% of the geographical differences. The educational disparities between LA and the US were associated with gray matter volume and connectivity variations, especially in LA and AD patients. Education emerged as a critical factor in classifying aging and dementia across regions. DISCUSSION: The results underscore the impact of education on brain structure and function in LA, highlighting the importance of incorporating educational factors into diagnosing, care, and prevention, and emphasizing the need for global diversity in research. HIGHLIGHTS: Lower education was linked to reduced brain volume and connectivity in healthy controls (HCs), Alzheimer's disease (AD), and frontotemporal lobar degeneration (FTLD). Latin American cohorts have lower educational levels compared to the those in the United States. Educational disparities majorly drive brain health differences between regions. Educational differences were significant in both conditions, but more in AD than FTLD. Education stands as a critical factor in classifying aging and dementia across regions.

Neurocognitive patterns across genetic levels in behavioral variant frontotemporal dementia: a multiple single cases study.

BACKGROUND: Behavioral variant frontotemporal dementia (bvFTD) has been related to different genetic factors. Identifying multimodal phenotypic heterogeneity triggered by various genetic influences is critical for improving diagnosis, prognosis, and treatments. However, the specific impact of different genetic levels (mutations vs. risk variants vs. sporadic presentations) on clinical and neurocognitive phenotypes is not entirely understood, specially in patites from underrepresented regions such as Colombia. METHODS: Here, in a multiple single cases study, we provide systematic comparisons regarding cognitive, neuropsychiatric, brain atrophy, and gene expression-atrophy overlap in a novel cohort of FTD patients (n = 42) from Colombia with different genetic levels, including patients with known genetic influences (G-FTD) such as those with genetic mutations (GR1) in particular genes (MAPT, TARDBP, and TREM2); patients with risk variants (GR2) in genes associated with FTD (tau Haplotypes H1 and H2 and APOE variants including ε2, ε3, ε4); and sporadic FTD patients (S-FTD (GR3)). RESULTS: We found that patients from GR1 and GR2 exhibited earlier disease onset, pervasive cognitive impairments (cognitive screening, executive functioning, ToM), and increased brain atrophy (prefrontal areas, cingulated cortices, basal ganglia, and inferior temporal gyrus) than S-FTD patients (GR3). No differences in disease duration were observed across groups. Additionally, significant neuropsychiatric symptoms were observed in the GR1. The GR1 also presented more clinical and neurocognitive compromise than GR2 patients; these groups, however, did not display differences in disease onset or duration. APOE and tau patients showed more neuropsychiatric symptoms and primary atrophy in parietal and temporal cortices than GR1 patients. The gene-atrophy overlap analysis revealed atrophy in regions with specific genetic overexpression in all G-FTD patients. A differential family presentation did not explain the results. CONCLUSIONS: Our results support the existence of genetic levels affecting the clinical, neurocognitive, and, to a lesser extent, neuropsychiatric presentation of bvFTD in the present underrepresented sample. These results support tailored assessments characterization based on the parallels of genetic levels and neurocognitive profiles in bvFTD.

Dynamic brain fluctuations outperform connectivity measures and mirror pathophysiological profiles across dementia subtypes: A multicenter study.

From molecular mechanisms to global brain networks, atypical fluctuations are the hallmark of neurodegeneration. Yet, traditional fMRI research on resting-state networks (RSNs) has favored static and average connectivity methods, which by overlooking the fluctuation dynamics triggered by neurodegeneration, have yielded inconsistent results. The present multicenter study introduces a data-driven machine learning pipeline based on dynamic connectivity fluctuation analysis (DCFA) on RS-fMRI data from 300 participants belonging to three groups: behavioral variant frontotemporal dementia (bvFTD) patients, Alzheimer's disease (AD) patients, and healthy controls. We considered non-linear oscillatory patterns across combined and individual resting-state networks (RSNs), namely: the salience network (SN), mostly affected in bvFTD; the default mode network (DMN), mostly affected in AD; the executive network (EN), partially compromised in both conditions; the motor network (MN); and the visual network (VN). These RSNs were entered as features for dementia classification using a recent robust machine learning approach (a Bayesian hyperparameter tuned Gradient Boosting Machines (GBM) algorithm), across four independent datasets with different MR scanners and recording parameters. The machine learning classification accuracy analysis revealed a systematic and unique tailored architecture of RSN disruption. The classification accuracy ranking showed that the most affected networks for bvFTD were the SN + EN network pair (mean accuracy = 86.43%, AUC = 0.91, sensitivity = 86.45%, specificity = 87.54%); for AD, the DMN + EN network pair (mean accuracy = 86.63%, AUC = 0.89, sensitivity = 88.37%, specificity = 84.62%); and for the bvFTD vs. AD classification, the DMN + SN network pair (mean accuracy = 82.67%, AUC = 0.86, sensitivity = 81.27%, specificity = 83.01%). Moreover, the DFCA classification systematically outperformed canonical connectivity approaches (including both static and linear dynamic connectivity). Our findings suggest that non-linear dynamical fluctuations surpass two traditional seed-based functional connectivity approaches and provide a pathophysiological characterization of global brain networks in neurodegenerative conditions (AD and bvFTD) across multicenter data.

[Socioeconomic determinants and gender gaps in depressive symptoms in Chile]. / Determinantes socioeconómicos y brechas de género de la sintomatología depresiva en Chile.

BACKGROUND: There are marked differences associated with socio-economic factors in the prevalence of depressive symptoms (DS) in men and women. AIM: To estimate the association between socioeconomic status and DS in Chile and to estimate the gender gaps in this association. MATERIAL AND METHODS: The Patient Health Questionnaire-9 (PHQ-9) was applied as part of a socioeconomic survey carried out in a representative community sample (n = 2913). Using this information, we analyzed the influence of social status (education level, occupation, household income) and other psychosocial factors (gender, perceived social support, stressful life events) on DS. RESULTS: The prevalence of DS was 23.2% in women and 13.4% in men. A socioeconomic gradient was found in the distribution of DS. This gradient was more pronounced for women than for men. Gender, social support and stressful life events were the most important predictors of severe DS, with an estimated risk twice as high among women and almost three times as high among those with low social support. CONCLUSIONS: There is a combined effect between socio-economic and gender inequalities on DS. This partially explains the greater vulnerability of poor women and the DS gap between men and women.

Evaluating the reliability of neurocognitive biomarkers of neurodegenerative diseases across countries: A machine learning approach.

Accurate early diagnosis of neurodegenerative diseases represents a growing challenge for current clinical practice. Promisingly, current tools can be complemented by computational decision-support methods to objectively analyze multidimensional measures and increase diagnostic confidence. Yet, widespread application of these tools cannot be recommended unless they are proven to perform consistently and reproducibly across samples from different countries. We implemented machine-learning algorithms to evaluate the prediction power of neurocognitive biomarkers (behavioral and imaging measures) for classifying two neurodegenerative conditions -Alzheimer Disease (AD) and behavioral variant frontotemporal dementia (bvFTD)- across three different countries (>200 participants). We use machine-learning tools integrating multimodal measures such as cognitive scores (executive functions and cognitive screening) and brain atrophy volume (voxel based morphometry from fronto-temporo-insular regions in bvFTD, and temporo-parietal regions in AD) to identify the most relevant features in predicting the incidence of the diseases. In the Country-1 cohort, predictions of AD and bvFTD became maximally improved upon inclusion of cognitive screenings outcomes combined with atrophy levels. Multimodal training data from this cohort allowed predicting both AD and bvFTD in the other two novel datasets from other countries with high accuracy (>90%), demonstrating the robustness of the approach as well as the differential specificity and reliability of behavioral and neural markers for each condition. In sum, this is the first study, across centers and countries, to validate the predictive power of cognitive signatures combined with atrophy levels for contrastive neurodegenerative conditions, validating a benchmark for future assessments of reliability and reproducibility.

Demand for obstetric care and density of health resources for childbearing age Mexican women.

INTRODUCTION: In Mexico, there is an increase recorded in the number of C-sections, as well as inequity and inequality in the distribution of resources for obstetric care. OBJECTIVE: To identify the states and municipalities in Mexico that concentrate the demand for obstetric care and the C-section rates and their relationship with health resources and women of childbearing age (WCBA). METHOD: Births of the 2008-2017 period were recorded, grouped into five municipal strata, as well as 2017 health resources and WCBA. RESULTS: The 2008-2017 national rate of C-sections was 45.3/100 births; 95 and 97 % of births and C-sections were concentrated in the "very high" stratum, where 80 % or more of health resources were used, with overuse standing out. The density of health resources assigned to WCBAs reflected inequity and inequality. CONCLUSIONS: The high concentration of obstetric demand and health resources supply could entail a higher recurrence of C-sections. Policies for C-section reduction should consider proper organization and administration of health resources.

INTRODUCCIÓN: México registra aumento de las cesáreas e inequidad y desigualdad en la distribución de recursos para la atención obstétrica. OBJETIVO: Identificar las entidades y municipios en México que concentran la demanda de atención obstétrica y tasas de cesáreas y su relación con los recursos en salud y mujeres en edad fértil (MEF). MÉTODO: Se registraron los nacimientos del periodo 2008-2017, agrupados en cinco estratos municipales, y los recursos en salud y MEF de 2017. RESULTADOS: La tasa nacional de cesáreas 2008-2017 fue de 45.3/100 nacimientos; 95 y 97 % de los nacimientos y cesáreas se concentraron en el estrato "muy alto", en el cual se utilizó 80 % o más de los recursos en salud y destacó la sobreutilización. La densidad de recursos en salud destinados a las MEF reflejó inequidad y desigualdad. CONCLUSIONES: La alta concentración de la demanda obstétrica y oferta de los recursos en salud pudiera conllevar mayor recurrencia a la cesárea. En las políticas de reducción de cesáreas es necesario considerar la organización y administración adecuadas de los recursos en salud.

A lesion model of envy and Schadenfreude: legal, deservingness and moral dimensions as revealed by neurodegeneration.

The study of moral emotions (i.e. Schadenfreude and envy) is critical to understand the ecological complexity of everyday interactions between cognitive, affective, and social cognition processes. Most previous studies in this area have used correlational imaging techniques and framed Schadenfreude and envy as unified and monolithic emotional domains. Here, we profit from a relevant neurodegeneration model to disentangle the brain regions engaged in three dimensions of Schadenfreude and envy: deservingness, morality, and legality. We tested a group of patients with behavioural variant frontotemporal dementia (bvFTD), patients with Alzheimer's disease, as a contrastive neurodegeneration model, and healthy controls on a novel task highlighting each of these dimensions in scenarios eliciting Schadenfreude and envy. Compared with the Alzheimer's disease and control groups, patients with bvFTD obtained significantly higher scores on all dimensions for both emotions. Correlational analyses revealed an association between envy and Schadenfreude scores and greater deficits in social cognition, inhibitory control, and behaviour disturbances in bvFTD patients. Brain anatomy findings (restricted to bvFTD and controls) confirmed the partially dissociable nature of the moral emotions' experiences and highlighted the importance of socio-moral brain areas in processing those emotions. In all subjects, an association emerged between Schadenfreude and the ventral striatum, and between envy and the anterior cingulate cortex. In addition, the results supported an association between scores for moral and legal transgression and the morphology of areas implicated in emotional appraisal, including the amygdala and the parahippocampus. By contrast, bvFTD patients exhibited a negative association between increased Schadenfreude and envy across dimensions and critical regions supporting social-value rewards and social-moral processes (dorsolateral prefrontal cortex, angular gyrus and precuneus). Together, this study provides lesion-based evidence for the multidimensional nature of the emotional experiences of envy and Schadenfreude. Our results offer new insights into the mechanisms subsuming complex emotions and moral cognition in neurodegeneration. Moreover, this study presents the exacerbation of envy and Schadenfreude as a new potential hallmark of bvFTD that could impact in diagnosis and progression.

Estudio de variabilidad geográfica de las hospitalizaciones potencialmente evitables en México durante tres quinquenios.

INTRODUCCIÓN: Las enfermedades que motivan hospitalización potencialmente evitable tienen la característica de ser sensibles a la prevención, diagnóstico y control ambulatorio en atención primaria a la salud. OBJETIVOS: Identificar la tendencia nacional de la hospitalización potencialmente evitable entre 2001 y 2015 y analizar el patrón geográfico a nivel municipal y priorizar municipios. MÉTODO: Se usaron los egresos hospitalarios de la Secretaría de Salud. Se calcularon tasas de prevalencia nacionales y razones municipales, estandarizadas por edad y sexo. Se emplearon estadísticos de variabilidad para analizar y elaborar mapas. RESULTADOS: De los egresos hospitalarios, 10.39, 9.81 y 9.26 % se clasificaron como hospitalizaciones potencialmente evitables para cada periodo quinquenal. La tasa nacional se incrementó en el lapso estudiado: de 36.27 a 47.24 por 10 000 habitantes. La diabetes mellitus, las gastroenteritis y otras enfermedades de las vías respiratorias inferiores fueron las causas de mayor frecuencia. Los patrones geográficos en los tres periodos fueron semejantes. Se identificaron 487 municipios prioritarios, 174 con alto uso y 313 con sobreuso hospitalario, que concentraron 35.83 % de las hospitalizaciones evitables, 8.58 y 27.25 %, respectivamente. CONCLUSIONES: En México existe amplia variabilidad geográfica de la hospitalización potencialmente evitable con un patrón casi inmutable. INTRODUCTION: Diseases that motivate potentially preventable hospitalization (PH) have the characteristic of being sensitive to prevention, diagnosis and control on an outpatient basis in primary care. OBJECTIVES: To identify the national trend of potentially avoidable hospitalization between 2001 and 2015; to analyze its geographical pattern at the municipal level and prioritize municipalities. METHOD: Hospital discharge records from the Ministry of Health were used. National prevalence rates and municipal PH ratios, standardized by age and gender, were calculated. Variability statistics were used to analyze and generate maps. RESULTS: Among all hospital discharges, 10.39%, 9.81% and 9.26% were classified as PH for each period. The national PH rate did increase in the studied period: from 36.27 to 47.24 per 10,000 population. Diabetes mellitus, gastroenteritis and other diseases of the lower respiratory tract were the most common causes. Geographic patterns of PH were similar for the three periods. A total of 487 priority municipalities were identified, 174 with hospital high use and 313 with overuse, 35.83 % were avoidable hospitalizations, 8.58% and 27.25%, respectively. CONCLUSIONS: In Mexico there is wide geographical variability in PH, with an almost unchanging geographical pattern.

Tackling variability: A multicenter study to provide a gold-standard network approach for frontotemporal dementia.

Biomarkers represent a critical research area in neurodegeneration disease as they can contribute to studying potential disease-modifying agents, fostering timely therapeutic interventions, and alleviating associated financial costs. Functional connectivity (FC) analysis represents a promising approach to identify early biomarkers in specific diseases. Yet, virtually no study has tested whether potential FC biomarkers prove to be reliable and reproducible across different centers. As such, their implementation remains uncertain due to multiple sources of variability across studies: the numerous international centers capable conducting FC research vary in their scanning equipment and their samples' socio-cultural background, and, more troublingly still, no gold-standard method exists to analyze FC. In this unprecedented study, we aim to address both issues by performing the first multicenter FC research in the behavioral-variant frontotemporal dementia (bvFTD), and by assessing multiple FC approaches to propose a gold-standard method for analysis. We enrolled 52 bvFTD patients and 60 controls from three international clinics (with different fMRI recording parameters), and three additional neurological patient groups. To evaluate FC, we focused on seed analysis, inter-regional connectivity, and several graph-theory approaches. Only graph-theory analysis, based on weighted-matrices, yielded consistent differences between bvFTD and controls across centers. Also, graph metrics robustly discriminated bvFTD from the other neurological conditions. The consistency of our findings across heterogeneous contexts highlights graph-theory as a potential gold-standard approach for brain network analysis in bvFTD. Hum Brain Mapp 38:3804-3822, 2017. © 2017 Wiley Periodicals, Inc.

Effects of a Combined Therapy With D-002 (Beeswax Alcohols) Plus D-003 (Sugarcane Wax Acids) on Osteoarthritis Symptoms.

Context • Nonsteroidal, anti-inflammatory drugs effectively relieve osteoarthritis (OA) symptoms but also induce adverse effects (AEs) that limit their long-term use, which drives a search for safer treatments. D-002, a mixture of beeswax alcohols, and D-003, a mixture of sugarcane wax acids, have been effective in experimental and clinical studies for patients with OA. Objective • The study intended to investigate the effects on OA symptoms of a combined therapy using D-002 and D-003 (D-002/D-003), which were administered for 6 wk. Design • The study was a randomized, double-blind, placebo-controlled trial. Setting • The study was conducted at the Surgical Medical Research Center in Havana, Cuba. Participants • Participants were patients with mild-to-moderate OA. Intervention • Participants were randomly assigned to 1 of 4 groups-(1) a control group, which received a placebo; (2) the D-002 group (intervention group), which received 50 mg/d of D-002; (3) the D-003 group (intervention group), which received 10 mg/d of D-003; or (4) the D-002/D-003 group (intervention group), which received a combined therapy of 50 mg/d of D-002 plus 10 mg/d of D-003. The control group received tablets that were indistinguishable in appearance from the D-002 and D-003 tablets and had a similar composition, except that the active ingredients were replaced by lactose. The groups took the medications once per day for 6 wk. Outcome Measures • Symptoms were assessed using the Western Ontario and McMaster Individual Osteoarthritis Index (WOMAC) and a visual analogue scale (VAS). The primary outcome was the reduction in the total WOMAC score. The subscale scores on the WOMAC for pain, stiffness, and physical function, the VAS scores, and the use of rescue medications were secondary outcomes. Results • Of the 120 enrolled participants, 116 completed the study. The treatments with D-002, D-003, and D-002/D-003 reduced the mean total WOMAC scores significantly from baseline to postintervention, by 75.1%, 72.8%, and 91.2%, respectively. Compared with the placebo, the treatments decreased the mean WOMAC scores for pain, joint stiffness, and physical function significantly. The VAS scores significantly decreased, showing a 71.4%, a 66.9%, and an 84.7% reduction for the D-002, D-003, and D-002/D-003 groups, respectively. All the reductions were significant from the first week and were enhanced during the trial. The D-002/D-003 treatment was more effective in improving all of the scores than either monotherapy. With respect to rescue medications, 3/30, 2/30, and 2/30 used the medications in the D-002, D-003, and D-002/D-003 groups, respectively, vs 17/30 in the control group. The treatments were well tolerated. Conclusions • Administered for 6 wk, 50 mg/d of D-002 and 10 mg/d of D-003 ameliorated OA symptoms, but the combined therapy, D-002/D-003, was more effective than either monotherapy. All treatments were well tolerated.

Integration of Intention and Outcome for Moral Judgment in Frontotemporal Dementia: Brain Structural Signatures.

BACKGROUND: Moral judgment has been proposed to rely on a distributed brain network. This function is impaired in behavioral variant frontotemporal dementia (bvFTD), a condition involving damage to some regions of this network. However, no studies have investigated moral judgment in bvFTD via structural neuroimaging. METHODS: We compared the performance of 21 bvFTD patients and 19 controls on a moral judgment task involving scenarios that discriminate between the contributions of intentions and outcomes. Voxel-based morphometry was used to assess (a) the atrophy pattern in bvFTD patients, (b) associations between gray matter (GM) volume and moral judgments, and (c) structural differences between bvFTD subgroups (patients with relatively preserved moral judgment and patients with severer moral judgment impairments). RESULTS: Patients judged attempted harm as more permissible and accidental harm as less permissible than controls. The groups' performance on accidental harm was associated with GM volume in the precuneus. In controls, it was al- so associated with the ventromedial prefrontal cortex (VMPFC). Also, both groups' performance on attempted harm was associated with GM volume in the temporoparietal junction. Patients exhibiting worse performance displayed smaller GM volumes in the precuneus and temporal pole. CONCLUSIONS: Results suggest that moral judgment abnormalities in bvFTD are associated with impaired integration of intentions and outcomes, which depends on an extended brain network. In bvFTD, moral judgment seems to critically depend on areas beyond the VMPFC.

Assessment of myocardial fibrosis and microvascular damage in systemic sclerosis by magnetic resonance imaging and coronary angiotomography.

OBJECTIVE: Cardiac involvement in SSc is characterized by myocardial fibrosis, arrhythmias and pericarditis. Prevalence studies have shown variable results. The objective of this study was to determine the prevalence of cardiac involvement in SSc patients using the non-invasive, highly sensitive diagnostic methods of cardiac MRI and coronary angiotomography. METHODS: We included 62 SSc patients and excluded those with heart disease prior to the onset of SSc, renal failure, diabetes mellitus, hyperlipidaemia, arterial hypertension, untreated thyroid disease, cor pulmonale, pregnancy or contraindications to performing cardiac MRI. All underwent clinical and laboratory evaluation, ECG, coronary angiotomography and cardiac MRI. RESULTS: The prevalence of myocardial fibrosis was 45% and was higher in dcSSc (59%) than in lcSSc patients (33%; P = 0.04). The mean left ventricular ejection fraction (LVEF) was lower in patients with myocardial fibrosis (56%) than in those without fibrosis (63%; P = 0.0009); myocardial fibrosis on MRI was more frequent in the basal-septal segments of the LV. Seventy-nine per cent of patients had subendocardial perfusion defects and these were associated with higher ultrasensitive serum CRP values. There was no association of myocardial fibrosis or microvascular damage with atherosclerosis. CONCLUSION: The prevalence of myocardial fibrosis on MRI attributable to SSc is 45%, is more frequent and severe in dcSSc patients, is associated with lower LVEF and affects mainly basal LV walls. Microvascular damage in SSc is common and is associated with elevated ultrasensitive CRP levels. Cardiac damage due to SSc is not associated with coronary artery disease.

Cross-cultural adaptation and validation of the sino-nasal outcome test (SNOT-22) for Spanish-speaking patients.

Our objective was to perform translation, cross-cultural adaptation and validation of the sino-nasal outcome test 22 (SNOT-22) to Spanish language. SNOT-22 was translated, back translated, and a pretest trial was performed. The study included 119 individuals divided into 60 cases, who met diagnostic criteria for chronic rhinosinusitis according to the European Position Paper on Rhinosinusitis 2012; and 59 controls, who reported no sino-nasal disease. Internal consistency was evaluated with Cronbach's alpha test, reproducibility with Kappa coefficient, reliability with intraclass correlation coefficient (ICC), validity with Mann-Whitney U test and responsiveness with Wilcoxon test. In cases, Cronbach's alpha was 0.91 both before and after treatment, as for controls, it was 0.90 at their first test assessment and 0.88 at 3 weeks. Kappa coefficient was calculated for each item, with an average score of 0.69. ICC was also performed for each item, with a score of 0.87 in the overall score and an average among all items of 0.71. Median score for cases was 47, and 2 for controls, finding the difference to be highly significant (Mann-Whitney U test, p < 0.001). Clinical changes were observed among treated patients, with a median score of 47 and 13.5 before and after treatment, respectively (Wilcoxon test, p < 0.001). The effect size resulted in 0.14 in treated patients whose status at 3 weeks was unvarying; 1.03 in those who were better and 1.89 for much better group. All controls were unvarying with an effect size of 0.05. The Spanish version of the SNOT-22 has the internal consistency, reliability, reproducibility, validity and responsiveness necessary to be a valid instrument to be used in clinical practice.

[Percentage of births and fertility rates in adolescents in Mexico (2008-2012): stratification and priorization of municipalities with high risk]. / Porcentaje de nacimientos y tasas de fecundidad en adolescentes de México (2008-2012): estratificación y priorización de municipios con alto riesgo.

BACKGROUND: Mexico in 2008 was designed as the first place of adolescent pregnancy at the Organization for Economic Cooperation and Development, with specific fertility rate (SFR) for 15-1 9years of age of 64.2/1,000 woman at the same age. OBJECTIVE: Estimate of percentage births and SFR in adolescent population at national, state and municipal level in Mexico in 2008-2012 at the total group of adolescents 10 to 1 9 years old and by subgroups of 10-14 and 15 tol 9 years old, identifying the priority municipalities with adolescence pregnancies. MATERIAL AND METHOD: Data bases of certificates of live birth and fetal death with gestational age of 22-45 weeks were joined in 2008-2012. RESULTS: A data base of 1 0'585,032 births in 2008-2012 was obtained, 98.9% were live births and 1.1% was stillbirths. The SFR nationwide for the period 2008-2012 were of the order of 3.l for the group of 10-1 4years, 75.3 for 15-19, 39.6 for the total group of 10-19 years and 66.1 for 20 to 49 years per 1000 women for the same age. CONCLUSION: In the last decade it has increased teen pregnancy as well as the percentage of births and the fertility rate in this age group, worrying situation for the high risk of biological, psychological and social damage that pregnancy early.

Cochlear implantation outcomes in advanced otosclerosis.

INTRODUCTION: Several studies support the use of cochlear implants (CI) in far-advanced otosclerosis (FAO). MATERIAL AND METHODS: We compared our results of CI in patients with FAO and unknown origin hearing loss (UOHL) and our incidence of facial electrical stimulation and difficult insertion of the electrode bundle up to 3 to 5 years from surgery. RESULTS: We found 17 patients with CI in FAO and UOHL. FAO patients achieved better results on the pure tone average (PTA) and recognition of monosyllables by GEE test (p=0.022; p=0.006), and particularly at 1 year on the PTA (p=0.002), at 6 months and a year in monosyllables (p=0.002; p=0.001), and at 6 months in disyllables (p=0.004). There were no differences toward complications. CONCLUSION: In our experience, placement of CI in FAO has proven successful, with results comparable to other similar cohorts, and with low complications.

Designing Prepregnation and Fused Filament Fabrication Parameters for Recycled PP- and PA-Based Continuous Carbon Fiber Composites.

Continuous carbon fiber (cCF)-based 3D-printed polymer composites are known for their excellent flexural properties; however, the optimization of the overall process is still desired, depending on the material types involved. Here, the improved manufacturing of cCF-based composites is reported, considering virgin polyamide (PA) and postindustrial waste polypropylene (PP), and the parameters affecting the material properties are evaluated. Firstly, the prepregnation technique was optimized to manufacture cCF polymer filaments with various fiber-to-polymer ratios. Secondly, the fused filament fabrication (FFF) technique was optimized. It was observed that the layer height needs to be sufficiently low for proper interlayer adhesion. The influence of the printing temperature is more complicated, with filaments characterized by a lower fiber-to-polymer ratio requiring a higher nozzle diameter and higher temperatures for efficient printing; and for lower diameters, the best flexural properties are observed for parts printed at lower temperatures, maintaining a high interspace distance. Plasma treatment of the cCF was also explored, as was annealing of the produced parts to enhance the flexural properties, the latter being specifically interesting for the PP-based composite due to a lower wetting caused by a higher viscosity, despite supportive interfacial interactions. Eventually, overall guidelines were formulated for the successful production of cCF-based composites.

Tolerance Mitigates Gall Effects When Susceptible Plants Fail to Elicit Induced Defense.

Variations in plant genotypes and phenotypes are expressed in ways that lead to the development of defensive abilities against herbivory. Induced defenses are mechanisms that affect herbivore insect preferences and performance. We evaluated the performance of resistant and susceptible phenotypes of Bauhinia brevipes (Fabaceae) against attacks by the gall-inducing insect Schizomyia macrocapillata (Diptera). We hypothesized that there is a positive relationship between resistance to S. macrocapillata and host plant performance because resistance can have a high adaptive value. We evaluated plant architecture, nutritional leaf quality, leaf fluctuating asymmetry, and reproductive capacity between phenotypes. Plant performance was evaluated at three ontogenetic stages: seed, seedling, and juvenile. Overall, there were no differences in vegetative and reproductive performance or asymmetry between the resistant and susceptible mature plants. We found no relationship between leaf nutritional quality and resistance to S. macrocapillata. Plant performance was consistent across ontogeny for both phenotypes, except for five variables. Contrary to our expectations, the susceptible plants performed equally well or better than the resistant plants, suggesting that tolerance and overcompensation to herbivory in B. brevipes may be mediated by induced defense. Our study highlights the importance of multiple layers of plant defense against herbivory, where plant tolerance acts as a secondary barrier in plants susceptible to gall-inducing insects.

Brain clocks capture diversity and disparity in aging and dementia.

Brain clocks, which quantify discrepancies between brain age and chronological age, hold promise for understanding brain health and disease. However, the impact of multimodal diversity (geographical, socioeconomic, sociodemographic, sex, neurodegeneration) on the brain age gap (BAG) is unknown. Here, we analyzed datasets from 5,306 participants across 15 countries (7 Latin American countries -LAC, 8 non-LAC). Based on higher-order interactions in brain signals, we developed a BAG deep learning architecture for functional magnetic resonance imaging (fMRI=2,953) and electroencephalography (EEG=2,353). The datasets comprised healthy controls, and individuals with mild cognitive impairment, Alzheimer's disease, and behavioral variant frontotemporal dementia. LAC models evidenced older brain ages (fMRI: MDE=5.60, RMSE=11.91; EEG: MDE=5.34, RMSE=9.82) compared to non-LAC, associated with frontoposterior networks. Structural socioeconomic inequality and other disparity-related factors (pollution, health disparities) were influential predictors of increased brain age gaps, especially in LAC (R2=0.37, F2=0.59, RMSE=6.9). A gradient of increasing BAG from controls to mild cognitive impairment to Alzheimer's disease was found. In LAC, we observed larger BAGs in females in control and Alzheimer's disease groups compared to respective males. Results were not explained by variations in signal quality, demographics, or acquisition methods. Findings provide a quantitative framework capturing the multimodal diversity of accelerated brain aging.