Association Between Depressive Symptoms and Cardiac Structure and Function in a Peruvian Population.

Depressive disorders are a leading cause of disability and are globally pervasive. It is estimated that 80% of depression occurs in low-income and middle-income countries. Depression is associated with worse outcomes in patients with cardiac disease including heart failure (HF); however, mechanistic understanding to explain heightened risk in HF remains poorly characterized. We examined the association between depressive symptoms and cardiac structure and function by transthoracic echocardiography. We selected a random sample of adult participants in Puno and Pampas de San Juan de Miraflores, Peru, from the CRONICAS cohort study. Depression symptoms were self-reported and measured with the Center for Epidemiological Studies Depression Scale in 2010. Participants underwent transthoracic echocardiography in 2014. Multivariable linear regression was used to examine the relationship between depressive symptoms and echocardiographic measures of cardiac structure and function and was adjusted for relevant covariates. Three hundred and seventy-three participants (mean age 56.7 years, 57% female) were included in this analysis of which 91 participants (24%) had clinically significant depressive symptoms. After adjustment, clinically significant depressive symptoms were associated with a reduced diastolic relaxation velocity compared to non-depressed subjects (-0.72 cm/s, 95% CI -1.21 to -0.24, p = 0.004). Other differences between depressed and non- depressed participants were less obvious. In conclusion, clinically significant depressive symptoms were associated with a lower septal e' velocity in the Peruvian population. Depressive symptoms were not obviously associated with other abnormalities in cardiac structure or function

Heterogeneity of Purkinje cell simple spike-complex spike interactions:zebrin- and non-zebrin-related variations

KEY POINTS: Cerebellar Purkinje cells (PCs) generate two types of action potentials, simple and complex spikes. Although they are generated by distinct mechanisms, interactions between the two spike types exist. Zebrin staining produces alternating positive and negative stripes of PCs across most of the cerebellar cortex. Thus, here we compared simple spike-complex spike interactions both within and across zebrin populations. Simple spike activity undergoes a complex modulation preceding and following a complex spike. The amplitudes of the pre- and post-complex spike modulation phases were correlated across PCs. On average, the modulation was larger for PCs in zebrin positive regions. Correlations between aspects of the complex spike waveform and simple spike activity were found, some of which varied between zebrin positive and negative PCs. The implications of the results are discussed with regard to hypotheses that complex spikes are triggered by rises in simple spike activity for either motor learning or homeostatic functions. ABSTRACT: Purkinje cells (PCs) generate two types of action potentials, called simple and complex spikes (SSs and CSs). We first investigated the CS-associated modulation of SS activity and its relationship to the zebrin status of the PC. The modulation pattern consisted of a pre-CS rise in SS activity, and then, following the CS, a pause, a rebound, and finally a late inhibition of SS activity for both zebrin positive (Z+) and negative (Z-) cells, though the amplitudes of the phases were larger in Z+ cells. Moreover, the amplitudes of the pre-CS rise with the late inhibitory phase of the modulation were correlated across PCs. In contrast, correlations between modulation phases across CSs of individual PCs were generally weak. Next, the relationship between CS spikelets and SS activity was investigated. The number of spikelets/CS correlated with the average SS firing rate only for Z+ cells. In contrast, correlations across CSs between spikelet numbers and the amplitudes of the SS modulation phases were generally weak. Division of spikelets into likely axonally propagated and non-propagated groups (based on their interspikelet interval) showed that the correlation of spikelet number with SS firing rate primarily reflected a relationship with non-propagated spikelets. In sum, the results show both zebrin-related and non-zebrin-related physiological heterogeneity in SS-CS interactions among PCs, which suggests that the cerebellar cortex is more functionally diverse than is assumed by standard theories of cerebellar function

Hematopoietic Cell Transplantation in Patients With Primary Immune Regulatory Disorders (PIRD): A Primary Immune Deficiency Treatment Consortium (PIDTC) Survey.

Primary Immune Regulatory Disorders (PIRD) are an expanding group of diseases caused by gene defects in several different immune pathways, such as regulatory T cell function. Patients with PIRD develop clinical manifestations associated with diminished and exaggerated immune responses. Management of these patients is complicated; oftentimes immunosuppressive therapies are insufficient, and patients may require hematopoietic cell transplant (HCT) for treatment. Analysis of HCT data in PIRD patients have previously focused on a single gene defect. This study surveyed transplanted patients with a phenotypic clinical picture consistent with PIRD treated in 33 Primary Immune Deficiency Treatment Consortium centers and European centers. Our data showed that PIRD patients often had immunodeficient and autoimmune features affecting multiple organ systems. Transplantation resulted in resolution of disease manifestations in more than half of the patients with an overall 5-years survival of 67%. This study, the first to encompass disorders across the PIRD spectrum, highlights the need for further research in PIRD management

International genome-wide meta-analysis identifies new primary biliary cirrhosis risk loci and targetable pathogenic pathways.

Primary biliary cirrhosis (PBC) is a classical autoimmune liver disease for which effective immunomodulatory therapy is lacking. Here we perform meta-analyses of discovery data sets from genome-wide association studies of European subjects (n=2,764 cases and 10,475 controls) followed by validation genotyping in an independent cohort (n=3,716 cases and 4,261 controls). We discover and validate six previously unknown risk loci for PBC (Pcombined<5 × 10(-8)) and used pathway analysis to identify JAK-STAT/IL12/IL27 signalling and cytokine-cytokine pathways, for which relevant therapies exist

y Integrated analysis of 8-week glecaprevir/pibrentasvir in Japanese and overseas patients without cirrhosis and with hepatitis C virus genotype 1 or 2 infection

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Lessons from the Subprime Meltdown

This paper uses Hyman P. Minsky's approach to analyze the current international financial crisis, which was initiated by problems in the American real estate market. In a 1987 manuscript, Minsky had already recognized the importance of the trend toward securitization of home mortgages. This paper identifies the causes and consequences of the financial innovations that created the real estate boom and bust. It examines the role played by each of the key playersincluding brokers, appraisers, borrowers, securitizers, insurers, and regulatorsin creating the crisis. Finally, it proposes short-run solutions to the current crisis, as well as longer-run policy to prevent it (a debt deflation) from happening again