Posttraumatic growth in cancer survivors and their significant others: vicarious or secondary growth?

Las enfermedades graves como el cáncer, aunque generan elevado malestar emocional y estrés en los supervivientes y en sus otros significativos, también pueden suponer un estímulo en la generación de crecimiento postraumático en ambos. Los mecanismos de cómo se produce este crecimiento postraumático (vicario vs. secundario) en los otros significativos no se han estudiado. En esta revisión se analizan la evidencia y relación del crecimiento post-traumático en supervivientes de cáncer y en sus otros significativos, principalmente sus parejas, madres y padres, en relación a estos mecanismos de transmisión vicario o secundario. Se concluye que, en general, el crecimiento post-traumático en los otros significativos es una experiencia vicaria íntimamente ligada al crecimiento del superviviente en cáncer, aunque ser mujer, madre o sufrir un cáncer avanzado facilitan procesos de crecimiento post-traumático secundario en los otros significativos, que se diferencian del superviviente

Predicting Progression in Parkinson's Disease Using Baseline and 1-Year Change Measures.

BackgroundImproved prediction of Parkinson's disease (PD) progression is needed to support clinical decision-making and to accelerate research trials.ObjectivesTo examine whether baseline measures and their 1-year change predict longer-term progression in early PD.MethodsParkinson's Progression Markers Initiative study data were used. Participants had disease duration ≤2 years, abnormal dopamine transporter (DAT) imaging, and were untreated with PD medications. Baseline and 1-year change in clinical, cerebrospinal fluid (CSF), and imaging measures were evaluated as candidate predictors of longer-term (up to 5 years) change in Movement Disorders Society-Unified Parkinson's Disease Rating Scale (MDS-UPDRS) score and DAT specific binding ratios (SBR) using linear mixed-effects models.ResultsAmong 413 PD participants, median follow-up was 5 years. Change in MDS-UPDRS from year-2 to last follow-up was associated with disease duration (β= 0.351; 95% CI = 0.146, 0.555), male gender (β= 3.090; 95% CI = 0.310, 5.869), and baseline (β= -0.199; 95% CI = -0.315, -0.082) and 1-year change (β= 0.540; 95% CI = 0.423, 0.658) in MDS-UPDRS; predictors in the model accounted for 17.6% of the variance in outcome. Predictors of percent change in mean SBR from year-2 to last follow-up included baseline rapid eye movement sleep behavior disorder score (β= -0.6229; 95% CI = -1.2910, 0.0452), baseline (β= 7.232; 95% CI = 2.268, 12.195) and 1-year change (β= 45.918; 95% CI = 35.994,55.843) in mean striatum SBR, and 1-year change in autonomic symptom score (β= -0.325;95% CI = -0.695, 0.045); predictors in the model accounted for 44.1% of the variance.ConclusionsBaseline clinical, CSF, and imaging measures in early PD predicted change in MDS-UPDRS and dopamine-transporter binding, but the predictive value of the models was low. Adding the short-term change of possible predictors improved the predictive value, especially for modeling change in dopamine-transporter binding

Novel recruitment strategy to enrich for LRRK2 mutation carriers

The LRRK2 G2019S mutation is found at higher frequency among Parkinson disease (PD) patients of Ashkenazi Jewish (AJ) ancestry. This study was designed to test whether an internet-based approach could be an effective approach to screen and identify mutation carriers. Individuals with and without PD of AJ ancestry were recruited and consented through an internet-based study website. An algorithm was applied to a series of screening questions to identify individuals at increased risk to carry the LRRK2 G2019S mutation. About 1000 individuals completed the initial screening. Around 741 qualified for mutation testing and 650 were tested. Seventy-two individuals carried at least one LRRK2 G2019S mutation; 38 with PD (12.5%) and 34 without (10.1%). Among the AJ PD participants, each affected first-degree relative increased the likelihood the individual was LRRK2+ [OR = 4.7; 95% confidence interval = (2.4–9.0)]. The same was not observed among the unaffected AJ subjects (P = 0.11). An internet-based approach successfully screened large numbers of individuals to identify those with risk factors increasing the likelihood that they carried a LRRK2 G2019S mutation. A similar approach could be implemented in other disorders to identify individuals for clinical trials, biomarker analyses and other types of research studies

Socioeconomic determinants of nutritional status in children under five attended at the Hospital Infantil Napoleón Franco Pareja

Objetivo: Determinar los factores sociales y económicos que afectan el estado nutricional de los niños menores de cinco años. Metodología: Se llevó a cabo un estudio de corte transversal con una muestra de 600 menores que asistieron al Hospital Infantil Napoleón Franco Pareja (HINFP) a cuyas madres se les aplicó un instrumento estandarizado para capturar la información socioeconómica y el estado nutricional del niño y de la madre. Se estimaron dos modelos econométricos de Umbral Generalizado, tomando como variable dependientes talla para la edad y peso para la talla y como variables independientes: peso al nacer del menor, número de controles prenatales, nivel de ingresos del hogar, uso de servicios de alcantarillado y acueducto, índice de masa corporal (IMC) de la madre, entre otras.  Resultados: De acuerdo al indicador de talla para la edad, el 48.05% de los niños sufren de desnutrición crónica. El indicador de peso para la talla reflejó que el 22.09% de los niños tuvieron un déficit en su masa corporal (desnutrición aguda) y un 13.53% se encontraba en sobrepeso u obesidad. El 76.02% de las madres con hijos con talla para la edad normal tienen educación media o superior. El 56% de los niños pertenecientes a hogares con ingresos inferiores al salario mínimo mensual legal vigente tuvieron problemas de desnutrición aguda. Respecto a los determinantes, mayores ingresos reducen la probabilidad de que un niño sufra desnutrición. El tiempo de lactancia materna, la ocupación y el estado nutricional de la madre resultaron ser factores protectores. El incremento de la edad gestacional al nacimiento, aumenta la probabilidad de tener una talla normal. Conclusiones: La presente investigación genera evidencia para revisar la política sanitaria de nutrición infantil. Elevar el nivel de ingresos y promover la lactancia materna mejorarían el estado nutricional de los niños.Objective: To determine the social and economic factors that affect he nutritional status of children under five years of age. Methods: A cross-sectional study carried out with a sample of 600 children were attended the Children’s Hospital Napoleón Franco Pareja (HINFP) whose mothers were administered a standardized instrument to capture the socioeconomic information and nutritional status of the child. Two econometric models were estimated using Generalized Threshold, taking as dependent variable-height for age and weight for height and as independent variables: birth weight of the child, number of prenatal controls, level of household income, use of sewerage and aqueduct services, mother’s body mass index (BMI), among others. Results: According to the height for age indicator, 48.05% of children suffer from chronic malnutrition. The indicator weight for height showed that 22.09% of children have a deficit in their body mass (acute malnutrition) and 13.53% were overweight or obese. 76.02% of mothers of children with normal height for age have completed secondary or higher education. 56% of children in households with incomes below current legal monthly minimum wage have acute malnutrition problems. Regarding the determinants, higher incomes reduce the likelihood that a child would suffer malnutrition. Breastfeeding time, occupation and maternal nutritional status are protective factors. Increasing gestational age at birth increases the likelihood of a normal size. Conclusions: This research generated evidence for health policy review of child nutrition. The raising of incomes and the promotion breastfeeding would improve the nutritional status of children.&nbsp

The Promise and Pitfalls of Facebook Advertising: a Genetic Counselor’s Perspective

Facebook advertising is a powerful tool for increasing the outreach and recruitment of research participants. We describe our experience as genetic counselors within the context of an internet-based research study, recruiting subjects for a Parkinson disease (PD) biomarker study

The Parkinson's progression markers initiative (PPMI) - establishing a PD biomarker cohort.

ObjectiveThe Parkinson's Progression Markers Initiative (PPMI) is an observational, international study designed to establish biomarker-defined cohorts and identify clinical, imaging, genetic, and biospecimen Parkinson's disease (PD) progression markers to accelerate disease-modifying therapeutic trials.MethodsA total of 423 untreated PD, 196 Healthy Control (HC) and 64 SWEDD (scans without evidence of dopaminergic deficit) subjects were enrolled at 24 sites. To enroll PD subjects as early as possible following diagnosis, subjects were eligible with only asymmetric bradykinesia or tremor plus a dopamine transporter (DAT) binding deficit on SPECT imaging. Acquisition of data was standardized as detailed at www.ppmi-info.org.ResultsApproximately 9% of enrolled subjects had a single PD sign at baseline. DAT imaging excluded 16% of potential PD subjects with SWEDD. The total MDS-UPDRS for PD was 32.4 compared to 4.6 for HC and 28.2 for SWEDD. On average, PD subjects demonstrated 45% and 68% reduction in mean striatal and contralateral putamen Specific Binding Ratios (SBR), respectively. Cerebrospinal fluid (CSF) was acquired from >97% of all subjects. CSF (PD/HC/SWEDD pg/mL) α-synuclein (1845/2204/2141) was reduced in PD vs HC or SWEDD (P < 0.03). Similarly, t-tau (45/53) and p-tau (16/18) were reduced in PD versus HC (P < 0.01).InterpretationPPMI has detailed the biomarker signature for an early PD cohort defined by clinical features and imaging biomarkers. This strategy provides the framework to establish biomarker cohorts and to define longitudinal progression biomarkers to support future PD treatment trials

Feasibility and Safety of Multicenter Tissue and Biofluid Sampling for α-Synuclein in Parkinson's Disease: The Systemic Synuclein Sampling Study (S4)

BACKGROUND: α-synuclein is a lead Parkinson's disease (PD) biomarker. There are conflicting reports regarding accuracy of α-synuclein in different tissues and biofluids as a PD biomarker, and the within-subject anatomical distribution of α-synuclein is not well described. The Systemic Synuclein Sampling Study (S4) aims to address these gaps in knowledge. The S4 is a multicenter, cross-sectional, observational study evaluating α-synuclein in multiple tissues and biofluids in PD and healthy controls (HC). OBJECTIVE: To describe the baseline characteristics of the S4 cohort and safety and feasibility of this study. METHODS: Participants underwent motor and non-motor clinical assessments, dopamine transporter SPECT, biofluid collection (cerebrospinal fluid, saliva, and blood), and tissue biopsies (skin, sigmoid colon, and submandibular gland). Biopsy adequacy was determined based on presence of adequate target tissue. Tissue sections were stained with the 5C12 monoclonal antibody against unmodified α-synuclein. All specimens were acquired and processed in a standardized manner. Adverse events were systematically recorded. RESULTS: The final cohort consists of 82 participants (61 PD, 21 HC). In 68 subjects (83%), all types of specimens were obtained but only 50 (61%) of subjects had all specimens both collected and evaluable for α-synuclein. Mild adverse events were common, especially for submandibular gland biopsy, but only 1 severe adverse event occurred. CONCLUSION: Multicenter tissue and biofluid sampling for α-synuclein is feasible and generally safe. S4 will inform understanding of the concurrent distribution of α-synuclein pathology and biomarkers in biofluids and peripheral nervous system in PD

Clonal chromosomal mosaicism and loss of chromosome Y in elderly men increase vulnerability for SARS-CoV-2

The pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2, COVID-19) had an estimated overall case fatality ratio of 1.38% (pre-vaccination), being 53% higher in males and increasing exponentially with age. Among 9578 individuals diagnosed with COVID-19 in the SCOURGE study, we found 133 cases (1.42%) with detectable clonal mosaicism for chromosome alterations (mCA) and 226 males (5.08%) with acquired loss of chromosome Y (LOY). Individuals with clonal mosaic events (mCA and/or LOY) showed a 54% increase in the risk of COVID-19 lethality. LOY is associated with transcriptomic biomarkers of immune dysfunction, pro-coagulation activity and cardiovascular risk. Interferon-induced genes involved in the initial immune response to SARS-CoV-2 are also down-regulated in LOY. Thus, mCA and LOY underlie at least part of the sex-biased severity and mortality of COVID-19 in aging patients. Given its potential therapeutic and prognostic relevance, evaluation of clonal mosaicism should be implemented as biomarker of COVID-19 severity in elderly people. Among 9578 individuals diagnosed with COVID-19 in the SCOURGE study, individuals with clonal mosaic events (clonal mosaicism for chromosome alterations and/or loss of chromosome Y) showed an increased risk of COVID-19 lethality

The genetic architecture of the human cerebral cortex

The cerebral cortex underlies our complex cognitive capabilities, yet little is known about the specific genetic loci that influence human cortical structure. To identify genetic variants that affect cortical structure, we conducted a genome-wide association meta-analysis of brain magnetic resonance imaging data from 51,665 individuals. We analyzed the surface area and average thickness of the whole cortex and 34 regions with known functional specializations. We identified 199 significant loci and found significant enrichment for loci influencing total surface area within regulatory elements that are active during prenatal cortical development, supporting the radial unit hypothesis. Loci that affect regional surface area cluster near genes in Wnt signaling pathways, which influence progenitor expansion and areal identity. Variation in cortical structure is genetically correlated with cognitive function, Parkinson's disease, insomnia, depression, neuroticism, and attention deficit hyperactivity disorder