Quality of Life and psychopathology in adults who underwent Hematopoietic Stem Cell Transplantation (HSCT) in childhood: a qualitative and quantitative analysis.

Background: Patients who undergo pediatric Hematopoietic Stem Cell Transplantation (HSCT) may experience long-term psychological sequelae and poor Quality of Life (QoL) in adulthood. This study aimed to investigate subjective illness experience, QoL, and psychopathology in young adults who have survived pediatric HSCT. Method: The study involved patients treated with HSCT in the Hematology-Oncology Department between 1984 and 2007. Psychopathology and QoL were investigated using the SCL-90-R and SF-36. Socio-demographic and medical information was also collected. Finally, participants were asked to write a brief composition about their experiences of illness and care. Qualitative analysis of the texts was performed using T-LAB, an instrument for text analysis that allows the user to highlight the occurrences and co-occurrences of lemma. Quantitative analyses were performed using non-parametric tests (Spearman correlations, Kruskal-Wallis and Mann-Whitney tests). Results: Twenty-one patients (9 males) participated in the study. No significant distress was found on the SCL-90 Global Severity Index, but it was found on specific scales. On the SF-36, lower scores were reported on scales referring to bodily pain, general health, and physical and social functioning. All the measures were significantly (p < 0.05) associated with specific socio-demographic and medical variables (gender, type of pathology, type of HSCT, time elapsed between communication of the need to transplant and effective transplantation, and days of hospitalization). With regard to the narrative analyses, males focused on expressions related to the body and medical therapies, while females focused on people they met during treatment, family members, and donors. Low general health and treatment with autologous HSCT were associated with memories about chemotherapy, radiotherapy, and the body parts involved, while high general health was associated with expressions focused on gratitude (V-Test \ub1 1.96). Conclusion: Pediatric HSCT survivors are more likely to experience psychological distress and low QoL in adulthood compared with the general population. These aspects, along with survivors' subjective illness experience, show differences according to specific medical and socio-demographic variables. Studies are needed in order to improve the care and long-term follow-up of these families

Prognostic value of gender and primary tumor location in metastatic colon cancer

Sex might influence prognosis in patients affected by colorectal cancer. We retrospectively studied a cohort of patients affected by metastatic colon cancer (mCC) stratified by sex and primary tumor location. RAS mutational status was also included in the analysis. Overall, 616 patients met the eligibility criteria, 261 women and 355 men. Neither gender, nor RAS mutational status influenced overall survival (OS) in the entire population. As expected, patients with right-sided colon cancer (RCC) had a significant shorter OS compared to those with left-sided colon cancer (LCC) (21.3 vs 33.1 months, p= 0.002). When the analysis was performed stratifying for gender, RCC retained worse prognosis among men (OS 20.5 vs 33.9 months, p= 0.008), but not among women (p= 0.132). Similarly, the presence of RAS mutations had no prognostic effect in women, but was significantly associate with shorter survival in men (OS 29.5 vs 33.7 months, p= 0.046). In addition, when comparing clinical outcome of women or men according to sidedness and RAS mutational status, RCC was associated with dismal prognosis only in men with RAS mutated tumor (OS 17.2 vs 32.3 months, p= 0.008). Our study highlights the importance of gender in the outcome of patients with mCC

Dynamic expression of genes associated with schizophrenia and bipolar disorder across development

Common genetic variation contributes a substantial proportion of risk for both schizophrenia and bipolar disorder. Furthermore, there is evidence of significant, but not complete, overlap in genetic risk between the two disorders. It has been hypothesised that genetic variants conferring risk for these disorders do so by influencing brain development, leading to the later emergence of symptoms. The comparative profile of risk gene expression for schizophrenia and bipolar disorder across development over different brain regions however remains unclear. Using genotypes derived from genome-wide associations studies of the largest available cohorts of patients and control subjects, we investigated whether genes enriched for schizophrenia and bipolar disorder association show a bias for expression across any of 13 developmental stages in prefrontal cortical and subcortical brain regions. We show that genetic association with schizophrenia is positively correlated with expression in the prefrontal cortex during early midfetal development and early infancy, and negatively correlated with expression during late childhood, which stabilises in adolescence. In contrast, risk-associated genes for bipolar disorder did not exhibit a bias towards expression at any prenatal stage, although the pattern of postnatal expression was similar to that of schizophrenia. These results highlight the dynamic expression of genes harbouring risk for schizophrenia and bipolar disorder across prefrontal cortex development and support the hypothesis that prenatal neurodevelopmental events are more strongly associated with schizophrenia than bipolar disorder

Regenerative medicine therapy: adipose derived extracellular vesicles in viral myocarditis

Objective: Myocarditis, inflammation of the heart muscle, is an autoimmune heart disease that can be caused by viruses, bacteria and toxins. Myocarditis can lead to dilated cardiomyopathy (DCM) and heart failure. Currently there are no disease-specific therapies for treating myocarditis or preventing progression to DCM. Adipose Extracellular Vesicles (AEVs) are lipid bilayer nanoparticles that are released into the outside environment of adipocytes and provide promising regenerative potential for inflammatory diseases like myocarditis. Methods: Lipoaspirate was obtained from women and men and AEVs isolated from the lipoaspirate using tangential flow filtration. We injected wild type male BALB/c mice with 250uL AEVs (1×10^10 EV/mL) intraperitoneally or sucrose control on day -1, 0, 1 with viral infection on day 0. Mice were harvested on day 10 post infection at the peak of myocarditis. Results: We found that male mice treated with AEVs from a female patient had a significantly higher body weight (p=0.0003), less calcification in the gut (p=0.001) and less myocardial inflammation (p=0.007) than controls. Mouse hearts analyzed by qRT-PCR revealed that AEV treated mice had significantly lower relative gene expression of cell markers for total immune cells (CD45, p=0.002), macrophages (CD11b, p=0.002, F4/80, p=0.0004); specifically M2 macrophages (Chi313, p=0.003), as well as CD3+ (p=0.007) and CD4+ T cells (p=0.01) than controls. Additionally, we found that mice treated with AEVs from a male patient also had significantly less myocardial inflammation (p=0.01). Conclusion: AEVs could provide an innovative therapy to reduce cardiac inflammation and decrease the risk of developing DCM following myocarditis

Exploration of first onsets of mania, schizophrenia spectrum disorders and major depressive disorder in perimenopause

Although the relationship between perimenopause and changes in mood has been well established, knowledge of risk of a broad spectrum of psychiatric disorders associated with reproductive aging is limited. Here we investigate whether the perimenopause (that is, the years around the final menstrual period (FMP)) is associated with increased risk of developing psychiatric disorders compared with the late reproductive stage. Information on menopausal timing and psychiatric history was obtained from nurse-administered interviews and online questionnaires from 128,294 female participants within UK Biobank. Incidence rates of psychiatric disorders during the perimenopause (4 years surrounding the FMP) were compared with the reference premenopausal period (6–10 years before the FMP). The rates were calculated for major depressive disorder (MDD), mania, schizophrenia spectrum disorders and other diagnoses. Overall, of 128,294 participants, 753 (0.59%) reported their first onset of a psychiatric disorder during the late reproductive stage (incidence rate 1.53 per 1,000 person-years) and 1,133 (0.88%) during the perimenopause (incidence rate 2.33 per 1,000 person-years). Compared with the reference reproductive period, incidence rates of psychiatric disorders significantly increased during the perimenopause (incidence rate ratio (RR) of 1.52, 95% confidence interval (CI) 1.39–1.67) and decreased back down to that observed in the premenopausal period in the postmenopause (RR of 1.09 (95% CI 0.98–1.21)). The effect was primarily driven by increased incidence rates of MDD, with an incidence RR of 1.30 (95% CI 1.16–1.45). However, the largest effect size at perimenopause was observed for mania (RR of 2.12 (95% CI 1.30–3.52)). No association was found between perimenopause and incidence rates of schizophrenia spectrum disorders (RR of 0.95 (95% CI 0.48–1.88)). In conclusion, perimenopause was associated with an increased risk of developing MDD and mania. No association was found between perimenopause and first onsets of schizophrenia spectrum disorders

Associations Between Schizophrenia Polygenic Liability, Symptom Dimensions, and Cognitive Ability in Schizophrenia

Importance Schizophrenia is a clinically heterogeneous disorder. It is currently unclear how variability in symptom dimensions and cognitive ability is associated with genetic liability for schizophrenia. Objective To determine whether phenotypic dimensions within schizophrenia are associated with genetic liability to schizophrenia, other neuropsychiatric disorders, and intelligence. Design, Setting, and Participants In a genetic association study, 3 cross-sectional samples of 1220 individuals with a diagnosis of schizophrenia were recruited from community, inpatient, and voluntary sector mental health services across the UK. Confirmatory factor analysis was used to create phenotypic dimensions from lifetime ratings of the Scale for the Assessment of Positive Symptoms, Scale for the Assessment of Negative Symptoms, and the MATRICS Consensus Cognitive Battery. Analyses of polygenic risk scores (PRSs) were used to assess whether genetic liability to schizophrenia, other neuropsychiatric disorders, and intelligence were associated with these phenotypic dimensions. Data collection for the cross-sectional studies occurred between 1993 and 2016. Data analysis for this study occurred between January 2019 and March 2021. Main Outcomes and Measures Outcome measures included phenotypic dimensions defined from confirmatory factor analysis relating to positive symptoms, negative symptoms of diminished expressivity, negative symptoms of motivation and pleasure, disorganized symptoms, and current cognitive ability. Exposure measures included PRSs for schizophrenia, bipolar disorder, major depression, attention-deficit/hyperactivity disorder, autism spectrum disorder, and intelligence. Results Of the 1220 study participants, 817 were men (67.0%). Participants’ mean (SD) age at interview was 43.10 (12.74) years. Schizophrenia PRS was associated with increased disorganized symptom dimension scores in both a 5-factor model (β = 0.14; 95% CI, 0.07-0.22; P = 2.80 × 10−4) and a 3-factor model across all samples (β = 0.10; 95% CI, 0.05-0.15; P = 2.80 × 10−4). Current cognitive ability was associated with genetic liability to schizophrenia (β = −0.11; 95% CI, −0.19 to −0.04; P = 1.63 × 10−3) and intelligence (β = 0.23; 95% CI, 0.16-0.30; P = 1.52 × 10−10). After controlling for estimated premorbid IQ, current cognitive performance was associated with schizophrenia PRS (β = −0.08; 95% CI, −0.14 to −0.02; P = 8.50 × 10−3) but not intelligence PRS. Conclusions and Relevance The findings of this study suggest that genetic liability for schizophrenia is associated with higher disorganized dimension scores but not other symptom dimensions. Cognitive performance in schizophrenia appears to reflect distinct contributions from genetic liabilities to both intelligence and schizophrenia

Mental health prior to and during the COVID-19 pandemic in individuals with bipolar disorder: Insights from prospective longitudinal data.

Objectives Many studies have examined the impact of COVID-19 on the mental health of the public, but few have focused on individuals with existing severe mental illness with longitudinal data before and during the pandemic. Aims: To investigate the impact of the COVID-19 pandemic on the mental health of people with bipolar disorder (BD). Methods In an ongoing study of people with BD who used an online mood monitoring tool, True Colours, 356 participants provided weekly data on their mental health. Symptoms of depression, mania, insomnia, and suicidal thoughts were compared in 2019 and 2020. From May 2020, participants also provided weekly data on the effect of the COVID-19 pandemic on anxiety, coping strategies, access to care, and medications. Results On average, symptoms of depression, mania, insomnia, and suicidal thoughts did not significantly differ in 2020 compared to 2019, but there was evidence of heterogeneity. There were high rates of anxiety about the pandemic and its impact on coping strategies, which increased to over 70% of responders in January 2021. A significant proportion of participants reported difficulty accessing routine care (27%) and medications (21%). Conclusions Although mood symptoms did not significantly increase during the pandemic overall, we observed heterogeneity among our BD sample and other impacted areas. Individuals' unique histories and psychosocial circumstances are key and should be explored in future qualitative studies. The significant impacts of the pandemic may take time to manifest, particularly among those who are socioeconomically disadvantaged, highlighting the need for further long-term prospective studies

Sequía e inundación en la hiperllanura pampeana : una mirada desde el lote al municipio

71-77En la Región Pampeana la lluvia, y su elevada variabilidad, es la principal determinante de la producción agropecuaria (Hall et al., 1992)que motoriza la economía de muchos municipios. En los sistemas de producción pampeanos, en los que el riego es aún una práctica poco común, la escasez de lluvias resiente a la producción y propaga sus efectos en el tiempo y en la comunidad a partir de los daños económicos que genera. En el otro extremo, las lluvias excesivas desencadenan procesos de anegamiento e inundación capaces de generar daños de magnitud similar a los de la sequía. En paisajes extremadamente planos o de 'hiperllanura' (Jobbágy et al., 2008), como son los de la Pampa Deprimida e Interior, el escurrimiento lento y dificultoso lleva a que los excesos hídricos se almacenen localmente, elevando los niveles freáticos e incrementando el área ocupada por agua en las zonas más bajas del paisaje. Las inundaciones resultantes son de avance gradual y sostenido y pueden durar muchos meses, generando pérdidas productivas y daños en la infraestructura de áreas rurales y urbanas. En el Oeste Pampeano y en gran parte de la cuenca del Río Salado las fluctuaciones del nivel de la napa freática están estrechamente conectadas al balance hídrico local y con los cuerpos superficiales de agua (Aragón et al., 2010; Badano, 2010). Los excesos hídricos son almacenados localmente en lagunas o en la napa freática, que lentamente sube de nivel. Las napas cercanas a la superficie aumentan fuertemente el rendimiento de los cultivos, especialmente en años secos (Nosetto et al., 2009), representando una vía de transferencia de agua de años de exceso a años de déficit (Jobbagy et al., 2008). Sin embargo, una vez que la napa supera un umbral de cercanía a la superficie el rendimiento cae abruptamente (Nosetto et al., 2009)y, a nivel de paisaje, el área ocupada por cuerpos de agua se expande con mucha rapidez, las lagunas comienzan a coalecer y en casos extremos se disparan inundaciones regionales (Aragón et al., 2010). Como el drenaje superficial natural y/o artificial de los excedentes tiene un alcance limitado en la región (Badano, 2010), cobra gran importancia el control de la recarga para evitar llegar a ese umbral crítico en el que aumenta el riesgo de inundación. Existen evidencias de que el reemplazo de pasturas perennes por cultivos ha aumentado la recarga (Nosetto et al., 2012), especialmente cuando luego de algunos años secos se siembran campos bajos que luego, en años húmedos, quedan sin sembrar o pierden sus cultivos tempranamente. Al margen del riesgo de inundación, los productores también se beneficiarían si lograran disminuir los excedentes hídricos. Aumentar la transpiración vegetal es una de las avenidas más potentes para lograr mayor productividad del agua limitando otras vías de pérdidas del sistema (Passioura, 2006), como el drenaje profundo o la evaporación desde grandes cuerpos de agua durante una inundación. Por eso, aunque pueden existir conflictos entre distintos usos de la tierra y los intereses de los municipios, también es claro que puede haber oportunidades para un beneficio mutuo. Lograr un uso más inteligente y justo del territorio requiere del conocimiento de los beneficios y riesgos que enfrentan sus múltiples usuarios y las alternativas disponibles. Frente al rol dual del agua en la Hiperllanura Pampeana, es valioso adaptar las estrategias de uso de la tierra para minimizar riesgos y daños maximizando la producción y el desarrollo económico. Para dar este paso surge una necesidad previa que es la de comprender la percepción que distintos actores del territorio tienen respecto a estas fluctuaciones ecohidrológicas. Con ese objetivo, realizamos un taller de discusión en la localidad de América, guiados por las siguientes preguntas: ¿en qué medida difieren los efectos, productivos y económicos, de la sequía y la inundación? ¿Cómo afectan estas perturbaciones aperturbaciones a distintos productores y a todo un municipio? ¿Cuáles son sus opciones y respuestas más comunes? Este trabajo presenta los hallazgos más sobresalientes

Genome-wide association study of borderline personality disorder reveals genetic overlap with the bipolar disorder, schizophrenia and major depression

Borderline personality disorder (BOR) is determined by environmental and genetic factors, and characterized by affective instability and impulsivity, diagnostic symptoms also observed in manic phases of Bipolar Disorder (BIP). Up to 20% of BIP patients show comorbidity with BOR. This report describes the first case-control genome-wide association study (GWAS) of BOR, performed in one of the largest BOR patient samples worldwide. The focus of our analysis was: (i) to detect genes and gene-sets involved in BOR; and (ii) to investigate the genetic overlap with BIP. As there is considerable genetic overlap between BIP, Major Depression (MDD) and Schizophrenia (SCZ) and a high comorbidity of BOR and MDD, we also analyzed the genetic overlap of BOR with SCZ and MDD. GWAS, gene-based tests,and gene-set-analyses were performed in 998 BOR patients and 1,545 controls. LD score regression was used to detect genetic overlap between BOR and these disorders. Single marker analysis revealed no significant association after correction for multiple testing. Genebased analysis yielded two significant genes: DPYD (p=4.42x10-7) and PKP4 (p=8.67x10-7); and gene-set-analysis yielded a significant finding for exocytosis (GO:0006887, pFDR=0.019). Prior studies have implicated DPYD, PKP4 and exocytosis in BIP and SCZ. The most notable finding of the present study was the genetic overlap of BOR with BIP (rg=0.28 [p=2.99x10-3]), SCZ (rg=0.34 [p=4.37x10-5]), and MDD (rg=0.57 [p=1.04x10-3]). Our study is the first to demonstrate that BOR overlaps with BIP, MDD and SCZ on the genetic level. Whether this is confined to transdiagnostic clinical symptoms should be examined in future studies

Emerging therapies in pheochromocytoma and paraganglioma: Immune checkpoint inhibitors in the starting blocks

Pheochromocytoma and paraganglioma are neuroendocrine neoplasms, originating in the adrenal medulla and in parasympathetic and sympathetic autonomic nervous system ganglia, respec-tively. They usually present as localized tumours curable with surgery. However, these tumours may exhibit heterogeneous clinical course, ranging from no/minimal progression to aggressive (progres-sive/metastatic) behavior. For this setting of patients, current therapies are unsatisfactory. Immune checkpoint inhibitors have shown outstanding results for several types of solid cancers. We therefore aimed to summarize and discuss available data on efficacy and safety of current FDA-approved immune checkpoint inhibitors in patients with pheochromocytoma and paraganglioma. After an extensive search, we found 15 useful data sources (four full-published articles, four supplements of scientific journals, seven ongoing registered clinical trials). The data we detected, even with the limit of the small number of patients treated, make a great expectation on the therapeutic use of immune checkpoint inhibitors. Besides, the newly detected predictors of response will (hopefully) be of great helps in selecting the subset of patients that might benefit the most from this class of drugs. Finally, new trials are in the starting blocks, and they are expected to shed in the next future new light on a therapy, which is considered a milestone in oncology