Tirzepatide and prevention of chronic kidney disease

Chronic kidney disease; Diabetes mellitus; ObesityMalaltia renal crònica; Diabetis mellitus; ObesitatEnfermedad renal crónica; Diabetes mellitus; ObesidadTirzepatide is a twincretin recently approved to improve glycemic control in type 2 diabetes mellitus (T2DM). More specifically, tirzepatide is an agonist of both the glucose-dependent insulinotropic polypeptide (GIP) and the glucagon-like peptide-1 (GLP1) receptors. In recent clinical trials in persons with obesity or overweight with associated conditions, tirzepatide decreased body weight and other cardiorenal risk factors (blood pressure, low-density lipoprotein cholesterol, glycated hemoglobin and albuminuria). Moreover, in a post hoc analysis of the SURPASS-4 randomized clinical trial, tirzepatide decreased albuminuria and total estimated glomerular filtration rate (eGFR) slopes and nearly halved the risk of a pre-specified composite kidney endpoint (eGFR decline ≥40%, renal death, kidney failure or new-onset macroalbuminuria) in participants with T2DM and high cardiovascular risk when compared with insulin glargine. Similar to other kidney-protective drugs, tirzepatide, alone or combined with sodium-glucose co-transporter 2 inhibitors, caused an early dip in eGFR. Moreover, tirzepatide also decreased eGFR slopes in participants with eGFR >60 mL/min/1.73 m2 or with normoalbuminuria. We now review the potential kidney health implications of tirzepatide, addressing its structure and function, relationship to current GLP1 receptor agonists, impact of recent results for the treatment and prevention of kidney disease, and expectations for the future.FIS/Fondos FEDER (PI18/01366, PI19/00588, PI19/00815, PI20/00744, DTS18/00032, ERA-PerMed-JTC2018 KIDNEY AT390 TACK AC18/00064 and PERSTIGAN AC18/00071, ISCIII-RETIC REDinREN RD016/0009), Sociedad Española de Nefrología, Sociedad Madrileña de Nefrología (SOMANE), FRIAT, Comunidad de Madrid en Biomedicina (B2017/BMD-3686 and CIFRA2-CM). Instituto de Salud Carlos III (ISCIII) RICORS program (RICORS2040-395 , RD21/0005/0001) and SPACKDc PMP21/00109, FEDER funds funded by European Union—Next Generation EU’, Mecanismo para la Recuperación y la Resiliencia (MRR) and RD16/0009

Host Cell Poly(ADP-ribose) glycohydrolase Is Crucial for Trypanosoma cruzi Infection Cycle

Trypanosoma cruzi, etiological agent of Chagas´ disease, has a complex life cycle which involves the invasion of mammalian host cells, differentiation and intracellular replication. Here we report the first insights into the biological role of a poly(ADPribose) glycohydrolase in a trypanosomatid (TcPARG). In silico analysis of the TcPARG gene pointed out the conservation of key residues involved in the catalytic process and, by Western blot, we demonstrated that it is expressed in a life stagedependant manner. Indirect immunofluorescense assays and electron microscopy using an anti-TcPARG antibody showed that this enzyme is localized in the nucleus independently of the presence of DNA damage or cell cycle stage. The addition of poly(ADP-ribose) glycohydrolase inhibitors ADP-HPD (adenosine diphosphate (hydroxymethyl)pyrrolidinediol) or DEA (6,9-diamino-2-ethoxyacridine lactate monohydrate) to the culture media, both at a 1 μM concentration, reduced in vitro epimastigote growth by 35% and 37% respectively, when compared to control cultures. We also showed that ADP-HPD 1 μM can lead to an alteration in the progression of the cell cycle in hydroxyurea synchronized cultures of T. cruzi epimastigotes. Outstandingly, here we demonstrate that the lack of poly(ADP-ribose) glycohydrolase activity in Vero and A549 host cells, achieved by chemical inhibition or iRNA, produces the reduction of the percentage of infected cells as well as the number of amastigotes per cell and trypomastigotes released, leading to a nearly complete abrogation of the infection process. We conclude that both, T. cruzi and the host, poly(ADP-ribose) glycohydrolase activities are important players in the life cycle of Trypanosoma cruzi, emerging as a promising therapeutic target for the treatment of Chagas´ disease.Fil: Vilchez Larrea, Salomé Catalina. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones en Ingeniería Genética y Biología Molecular; ArgentinaFil: Schlesinger, Mariana. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones en Ingeniería Genética y Biología Molecular; ArgentinaFil: Kevorkian, María Laura. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones en Ingeniería Genética y Biología Molecular; ArgentinaFil: Flawia, Mirtha Maria. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones en Ingeniería Genética y Biología Molecular; Argentina. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Departamento de Fisiología, Biología Molecular y Celular; ArgentinaFil: Alonso, Guillermo Daniel. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones en Ingeniería Genética y Biología Molecular; Argentina. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Departamento de Fisiología, Biología Molecular y Celular; ArgentinaFil: Fernandez Villamil, Silvia Hebe. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones en Ingeniería Genética y Biología Molecular; Argentina. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Química Biológica; Argentin

Efecto diferencial de dos cepas de Rhizophagus intraradices sobre la biomasa y el rendimiento y composición de aceites esenciales de Calamintha nepeta

El objetivo de este trabajo fue determinar, bajo condiciones de invernadero, el efecto de dos cepas geográficamente diferentes de Rhizophagus intraradices (M3 y GA5) sobre la biomasa total y el rendimiento y composición de aceites esenciales (AE) de Calamintha nepeta, con fertilización fosforada (P) o sin esta. La biomasa de la planta no fue significativamente afectada por ningún tratamiento, y se observaron valores más altos en las plantas control. Las cepas mostraron diferencias en sus tasas de colonización y en las respuestas a la fertilización con fósforo: M3 redujo sus valores de colonización, mientras que GA5 no los modificó. En ausencia de fertilización fosforada, las plantas colonizadas por ambas cepas presentaron rendimientos de AE diferentes a aquellos de las plantas control: M3 los aumentó y GA5 los disminuyó. La composición porcentual de AE no fue modificada significativamente por ninguno de los tratamientos. M3 podría ser considerada como un posible bioinoculante fúngico para la producción de C. nepeta destinada al mercado de las plantas aromáticas.The aim of this work was to determine the effects of two geographically different strains of Rhizophagus intraradices (M3 and GA5) on the total biomass and essential oil (EO) yield and composition of Calamintha nepeta, with or without phosphorus (P) fertilization, under greenhouse conditions.The plant biomass was not significantly affected by any of the treatments, showing higher values in control plants. Strains had a differential response in their root colonization rates: M3 reduced these parameters while GA5 did not modify them. Both strains affected EO yield in absence of P fertilization: M3 promoted EO yield in C. nepeta plants and GA5 resulted in negative effects. The percentage composition of EO was not significantly modified by either strain or P fertilization. M3 strain could be a potential fungal bioinoculant for production and commercialization of C. nepeta in the aromatic plant market.Fil: Colombo, Roxana. Universidad de Buenos Aires. Facultad de Cs.exactas y Naturales. Departamento de Biodiversidad y Biologia Experimental; ArgentinaFil: Martinez, Alicia Elba. Universidad de Buenos Aires. Facultad de Cs.exactas y Naturales. Departamento de Biodiversidad y Biologia Experimental; ArgentinaFil: Fernández Di Pardo, Agustina. Universidad de Buenos Aires. Facultad de Cs.exactas y Naturales. Departamento de Biodiversidad y Biologia Experimental; ArgentinaFil: Fernandez Bidondo, Laura. Universidad de Buenos Aires. Facultad de Cs.exactas y Naturales. Departamento de Biodiversidad y Biologia Experimental; ArgentinaFil: Van Baren, Catalina Maria. Universidad de Buenos Aires. Facultad de Farmacia y Bioquimica. Instituto de Química y Metabolismo del Fármaco; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Química y Metabolismo del Fármaco (i); ArgentinaFil: Di Leo Lira, Paola Maria del Rosario. Universidad de Buenos Aires. Facultad de Farmacia y Bioquimica. Instituto de Química y Metabolismo del Fármaco; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Química y Metabolismo del Fármaco (i); ArgentinaFil: Godeas, Alicia Margarita. Universidad de Buenos Aires. Facultad de Cs.exactas y Naturales. Departamento de Biodiversidad y Biologia Experimental; Argentin

Prototipo para levantamiento arquitectónico: Desarrollo y evaluación caso de estudio del Hospital Metropolitano de Tunja

This article describes the development and implementation of a compact and portable prototype for the survey of a point cloud of the Metropolitan Hospital of Tunja, Colombia, as a result of the SENNOVA project called “Development of preliminary diagnoses in existing buildings from the merger of 4 remote sensing technologies: laser scanner, photogrammetry, thermography and ground penetrating radar, through information models (BIM)”, developed by the collaboration of the Industrial Center for Maintenance and Manufacturing (Sena Regional Boyacá). Key components of this solution include a Hesai lidar, a 9-axis inertial unit (IMU), and a UP4000 computer. The construction of the point cloud was carried out through the implementation of LIO-SAM, which is developed in the ROS framework.Data acquisition was performed in three different configurations of the LIDAR and the IMU. This approach sought to determine the most effective orientation to achieve a complete and accurate representation. Simultaneously, tests were carried out by modifying the closed loop parameter in LIO-SAM and running the software on both the UP4000 and an external computer.The results revealed that the configuration that minimizes the error is achieved by positioning the LIDAR and IMU horizontally, with the Z axis oriented vertically. However, the need for additional tests to comprehensively evaluate the influence of the closed-loop parameter was highlighted. In addition, it was observed that the UP4000 has sufficient processing capacity to execute LIO-SAM, although the simultaneous execution of more processes could affect the results obtained.El presente articulo describe la construcción e´ implementación de un prototipo compacto y portátil para el levantamiento de una nube de puntos del Hospital Metropolitano de Tunja, Colombia, como resultado del proyecto SENNOVA denominado “Desarrollo de diagnósticos preliminares en edificaciones existentes a partir de la fusión de 4 tecnologías de sensoramiento remoto: escáner láser, fotogrametría, termografía y radar de penetración de terrenos, a través de modelos de información (BIM)”, desarrollado en conjunto con el Centro Industrial de Mantenimiento y Manufactura (Sena Regional Boyacá). Los componentes clave de esta solución  incluyen un LIDAR Hesai, una unidad inercial de 9 ejes (IMU) y una computadora UP4000. La construcción de la nube de puntos´ se llevó a cabo mediante la implementación de LIO-SAM, el cual se encuentra desarrollado en el marco de ROS. La adquisición de datos fue realizada en tres configuraciones distintas del LIDAR y la IMU. Este enfoque buscaba determinar la orientación  más efectiva para lograr una representación completa y precisa. Simultáneamente, se llevaron a cabo pruebas´ modificando el parámetro de lazo cerrado en LIO-SAM y ejecutando el software tanto en la UP4000 como en un computador externo. Los resultados revelaron que la configuración que minimiza el error se logra al posicionar el LIDAR y la IMU horizontalmente, con el eje Z orientado verticalmente. No obstante, se destacó la necesidad de realizar pruebas adicionales para evaluar exhaustivamente la influencia del parámetro de lazo cerrado. Además, se observó o que la UP4000 posee suficiente capacidad de procesamiento para ejecutar LIO-SAM, aunque la ejecución simultanea de más procesos podría afectar los resultados obtenidos

SPARC inhibition accelerates NAFLD-associated hepatocellular carcinoma development by dysregulating hepatic lipid metabolism

Background and aims: Non-alcoholic fatty liver (NAFLD) and its more serious form non-alcoholic steatohepatitis increase risk of hepatocellular carcinoma (HCC). Lipid metabolic alterations and its role in HCC development remain unclear. SPARC (Secreted Protein, Acidic and Rich in Cysteine) is involved in lipid metabolism, NAFLD and diabetes, but the effects on hepatic lipid metabolism and HCC development is unknown. The aim of this study was to evaluate the role of SPARC in HCC development in the context of NAFLD. Methods: Primary hepatocyte cultures from knockout (SPARC−/−) or wild-type (SPARC+/+) mice, and HepG2 cells were used to assess the effects of free fatty acids on lipid accumulation, expression of lipogenic genes and de novo triglyceride (TG) synthesis. A NAFLD-HCC model was stabilized on SPARC−/− or SPARC+/+ mice. Correlations among SPARC, lipid metabolism-related gene expression patterns and clinical prognosis were studied using HCC gene expression dataset. Results: SPARC−/− mice increases hepatic lipid deposits over time. Hepatocytes from SPARC−/− mice or inhibition of SPARC by an antisense adenovirus in HepG2 cells resulted in increased TG deposit, expression of lipid-related genes and nuclear translocation of SREBP1c. Human HCC database analysis revealed that SPARC negatively correlated with genes involved in lipid metabolism, and with poor survival. In NAFLD-HCC murine model, the absence of SPARC accelerates HCC development. RNA-seq study revealed that pathways related to lipid metabolism, cellular detoxification and proliferation were upregulated in SPARC−/− tumour-bearing mice. Conclusions: The absence of SPARC is associated with an altered hepatic lipid metabolism, and an accelerated NAFLD-related HCC development.Fil: Onorato, Agostina Mariana. Universidad Austral. Facultad de Ciencias Biomédicas. Instituto de Investigaciones en Medicina Traslacional. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones en Medicina Traslacional; ArgentinaFil: Fiore, Esteban Juan. Universidad Austral. Facultad de Ciencias Biomédicas. Instituto de Investigaciones en Medicina Traslacional. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones en Medicina Traslacional; ArgentinaFil: Bayo Fina, Juan Miguel. Universidad Austral. Facultad de Ciencias Biomédicas. Instituto de Investigaciones en Medicina Traslacional. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones en Medicina Traslacional; ArgentinaFil: Casali, Cecilia Irene. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Química y Físico-Química Biológicas "Prof. Alejandro C. Paladini". Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Química y Físico-Química Biológicas; ArgentinaFil: Fernandez, Maria del Carmen. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Química y Físico-Química Biológicas "Prof. Alejandro C. Paladini". Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Química y Físico-Química Biológicas; ArgentinaFil: Rodriguez, Marcelo Maximiliano. Universidad Austral. Facultad de Ciencias Biomédicas. Instituto de Investigaciones en Medicina Traslacional. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones en Medicina Traslacional; ArgentinaFil: Domínguez, Luciana María. Universidad Austral. Facultad de Ciencias Biomédicas. Instituto de Investigaciones en Medicina Traslacional. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones en Medicina Traslacional; ArgentinaFil: Argemi, Josepmaría. Universidad de Navarra; EspañaFil: Hidalgo, Florencia. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Favre, Cristian. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: García, Mariana. Universidad Austral. Facultad de Ciencias Biomédicas. Instituto de Investigaciones en Medicina Traslacional. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones en Medicina Traslacional; ArgentinaFil: Atorrasagasti, María Catalina. Universidad Austral. Facultad de Ciencias Biomédicas. Instituto de Investigaciones en Medicina Traslacional. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones en Medicina Traslacional; ArgentinaFil: Mazzolini Rizzo, Guillermo Daniel. Universidad Austral. Facultad de Ciencias Biomédicas. Instituto de Investigaciones en Medicina Traslacional. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones en Medicina Traslacional; Argentin

Beyond the consultation room : Proposals to approach health promotion in primary care according to health-care users, key community informants and primary care centre workers

Primary health care () is the ideal setting to provide integrated services centred on the person and to implement health promotion () activities. To identify proposals to approach in the context of primary care according to health-care users aged 45-75 years, key community informants and primary care centre () workers. Descriptive-interpretive qualitative research with 276 participants from 14 of seven Spanish regions. A theoretical sampling was used for selection. A total of 25 discussion groups, two triangular groups and 30 semi-structured interviews were carried out. A thematic interpretive contents analysis was carried out. Participants consider that is not solely a matter for the health sector and they emphasize intersectoral collaboration. They believe that it is important to strengthen community initiatives and to create a healthy social environment that encourages greater responsibility and participation of health-care users in decisions regarding their own health and better management of public services and resources. , care in the community and demedicalization should be priorities for . Participants propose organizational changes in the to improve . workers are aware that falls within the scope of their responsibilities and propose to increase their training, motivation, competences and knowledge of the social environment. Informants emphasize that should be person-centred approach and empathic communication. activities should be appealing, ludic and of proven effectiveness. According to a socio-ecological and intersectoral model, services must get actively involved in together with community and through outreach interventions

Obstetric outcomes of sars-cov-2 infection in asymptomatic pregnant women

Altres ajuts: Fondo Europeo de Desarrollo Regional (FEDER)Around two percent of asymptomatic women in labor test positive for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in Spain. Families and care providers face childbirth with uncertainty. We determined if SARS-CoV-2 infection at delivery among asymptomatic mothers had different obstetric outcomes compared to negative patients. This was a multicenter prospective study based on universal antenatal screening for SARS-CoV-2 infection. A total of 42 hospitals tested women admitted for delivery using polymerase chain reaction, from March to May 2020. We included positive mothers and a sample of negative mothers asymptomatic throughout the antenatal period, with 6-week postpartum follow-up. Association between SARS-CoV-2 and obstetric outcomes was evaluated by multivariate logistic regression analyses. In total, 174 asymptomatic SARS-CoV-2 positive pregnancies were compared with 430 asymptomatic negative pregnancies. No differences were observed between both groups in key maternal and neonatal outcomes at delivery and follow-up, with the exception of prelabor rupture of membranes at term (adjusted odds ratio 1.88, 95% confidence interval 1.13-3.11; p = 0.015). Asymptomatic SARS-CoV-2 positive mothers have higher odds of prelabor rupture of membranes at term, without an increase in perinatal complications, compared to negative mothers. Pregnant women testing positive for SARS-CoV-2 at admission for delivery should be reassured by their healthcare workers in the absence of symptoms

Disorders of sex development : genetic characterization of a patient cohort

Q3Q397-106Disorders of sex development (DSDs) are congenital conditions in which the external appearance of the individual does not coincide with the chromosomal constitution or the gonadal sex. In other words, there is an ambiguous or intermediate condition between the male and female phenotypes of the anatomical sex. These atypical conditions are manifested in several ways, ranging from genital ambiguity to phenotypes that are so attenuated that they can go unnoticed or appear normal. Currently, there is a lack of understanding of the factors responsible for these outcomes; however, they are likely to be conditioned by genetic, hormonal and environmental factors during prenatal and postnatal development. The present study determined the genetic etiology of DSDs in Colombian patients by conventional cytogenetic analysis, FISH and MLPA (for SF1, DAX1, SOX9, SRY and WNT4). A cohort of 43 patients with clinical phenotypes of sex development disorder was used in the present study. Using this multistep experimental approach, a diagnostic percentage of 25.58% was obtained: 17 patients (39.53%) were classified as having gonadal development disorders, the majority of which were ovotesticular disorders with numerical and/or structural alterations of the sex chromosomes, 9 patients (20.93%) were classified as having testicular DSD with a 46,XY karyotype, and 3 patients (6.98%) as having ovarian DSD with a 46,XX karyotype. The remaining 14 patients (32.56%) were classified as ‘other’ since they could not be grouped into a specific class of gonadal development, corresponding to hypospadias and multiple congenital anomalies. These findings highlight the importance of histological and cytogenetic studies in a gonadal biopsy. In 11/43 cases, the multistep experimental protocol presented in the present study yielded etiological or histological findings that could be used to define the medical management of patients with DSDs. In conclusion, for the etiological diagnosis of DSDs, a broad‑spectrum approach that includes endocrinological tests, conventional karyotyping, molecular karyotyping by FISH and, molecular tests is required, in addition to gonadal tissue analyses, to identify genetic alterations

SARS-CoV-2 Breakthrough Infections: Incidence and Risk Factors in a Large European Multicentric Cohort of Health Workers

The research aimed to investigate the incidence of SARS-CoV-2 breakthrough infections and their determinants in a large European cohort of more than 60,000 health workers

Analysis of shared heritability in common disorders of the brain

ience, this issue p. eaap8757 Structured Abstract INTRODUCTION Brain disorders may exhibit shared symptoms and substantial epidemiological comorbidity, inciting debate about their etiologic overlap. However, detailed study of phenotypes with different ages of onset, severity, and presentation poses a considerable challenge. Recently developed heritability methods allow us to accurately measure correlation of genome-wide common variant risk between two phenotypes from pools of different individuals and assess how connected they, or at least their genetic risks, are on the genomic level. We used genome-wide association data for 265,218 patients and 784,643 control participants, as well as 17 phenotypes from a total of 1,191,588 individuals, to quantify the degree of overlap for genetic risk factors of 25 common brain disorders. RATIONALE Over the past century, the classification of brain disorders has evolved to reflect the medical and scientific communities' assessments of the presumed root causes of clinical phenomena such as behavioral change, loss of motor function, or alterations of consciousness. Directly observable phenomena (such as the presence of emboli, protein tangles, or unusual electrical activity patterns) generally define and separate neurological disorders from psychiatric disorders. Understanding the genetic underpinnings and categorical distinctions for brain disorders and related phenotypes may inform the search for their biological mechanisms. RESULTS Common variant risk for psychiatric disorders was shown to correlate significantly, especially among attention deficit hyperactivity disorder (ADHD), bipolar disorder, major depressive disorder (MDD), and schizophrenia. By contrast, neurological disorders appear more distinct from one another and from the psychiatric disorders, except for migraine, which was significantly correlated to ADHD, MDD, and Tourette syndrome. We demonstrate that, in the general population, the personality trait neuroticism is significantly correlated with almost every psychiatric disorder and migraine. We also identify significant genetic sharing between disorders and early life cognitive measures (e.g., years of education and college attainment) in the general population, demonstrating positive correlation with several psychiatric disorders (e.g., anorexia nervosa and bipolar disorder) and negative correlation with several neurological phenotypes (e.g., Alzheimer's disease and ischemic stroke), even though the latter are considered to result from specific processes that occur later in life. Extensive simulations were also performed to inform how statistical power, diagnostic misclassification, and phenotypic heterogeneity influence genetic correlations. CONCLUSION The high degree of genetic correlation among many of the psychiatric disorders adds further evidence that their current clinical boundaries do not reflect distinct underlying pathogenic processes, at least on the genetic level. This suggests a deeply interconnected nature for psychiatric disorders, in contrast to neurological disorders, and underscores the need to refine psychiatric diagnostics. Genetically informed analyses may provide important "scaffolding" to support such restructuring of psychiatric nosology, which likely requires incorporating many levels of information. By contrast, we find limited evidence for widespread common genetic risk sharing among neurological disorders or across neurological and psychiatric disorders. We show that both psychiatric and neurological disorders have robust correlations with cognitive and personality measures. Further study is needed to evaluate whether overlapping genetic contributions to psychiatric pathology may influence treatment choices. Ultimately, such developments may pave the way toward reduced heterogeneity and improved diagnosis and treatment of psychiatric disorders