Fiscal Smell Tests: A Mid-Term Reality Check of Massachusetts Finances

In his latest budget message the Governor points to achievement of a real, but fragile fiscal balance. On the credit side of the ledger, he cites four balanced budgets, reduced reliance on one-time revenues, no new taxes, five tax cuts, no deficit borrowing, and a triple upgrade in bond rating. On the debit side are continued spending pressures, slow tax revenue growth and burdensome levels of debt. But is the fiscal condition of the Commonwealth stable, albeit fragile? Or would a careful reading of the numbers transmit another message? The purpose of this report is to measure the Commonwealth\u27s financial health against a generally accepted list of performance indicators in order to render an independent judgment about the state\u27s fiscal progress and condition

Anxiety and Depression as Comorbid Factors in Drinking Behaviors of Undergraduate College Students Attending an Urban Private University in the Northeastern United States

High-risk drinking is the number one public health concern on college campuses (Berkowitz, 2003; Kapner, 2003; Wechsler, 2002). To date, high-risk drinking prevention programs have met with limited success (Kapner, 2003). This study examined differences among four drinking behavior groups: non-drinkers [(ND), (n = 128)], low-risk drinkers [(LRD), (n = 252)], high-risk drinkers [(HRD), (n = 272)], and frequent high-risk drinkers [(FHRD), (n = 290)] with respect to anxiety and depression for male (n = 457) and female (n = 485) undergraduates (N = 942) attending an urban private university in the northeastern United States; and, the perceptions of two undergraduate focus groups (N = 10) and one faculty/staff group (N = 14) for why undergraduates engage in high-risk drinking and actions to reduce this behavior. Volunteer participants completed a demographic questionnaire, the Alcohol Use Disorders Identification Test, the Beck Anxiety Inventory, and the Beck Depression Inventory. An ANOVA indicated differences among the groups with respect to anxiety (F = 6.49, p \u3c .001), but not with respect to depression. The FHRD group had higher anxiety (M = .68) than the ND group (M = .33) and the LRD group (M = .44). A t-test indicated differences (p \u3c .01) in the level of anxiety between HRD females (M = .69) and HRD males (M = .40), with no differences for depression. A chi-square analysis indicated differences between males and females with respect to drinking behavior group classification (χ² = 22.40, df = 3, p = .001). Focus group results suggested several reasons why students engage in high-risk drinking: it is the norm, easy access to alcohol, low accountability for drinking, cope with anxiety, relieve boredom, lift depression, cope with anger, family history of alcohol use, alcohol dependence, and poor self-esteem. Implications for educators are discussed

Disruption of the Sarcoglycan–Sarcospan Complex in Vascular Smooth Muscle A Novel Mechanism for Cardiomyopathy and Muscular Dystrophy

AbstractTo investigate mechanisms in the pathogenesis of cardiomyopathy associated with mutations of the dystrophin–glycoprotein complex, we analyzed genetically engineered mice deficient for either α-sarcoglycan (Sgca) or δ-sarcoglycan (Sgcd). We found that only Sgcd null mice developed cardiomyopathy with focal areas of necrosis as the histological hallmark in cardiac and skeletal muscle. Absence of the sarcoglycan–sarcospan (SG-SSPN) complex in skeletal and cardiac membranes was observed in both animal models. Loss of vascular smooth muscle SG-SSPN complex was only detected in Sgcd null mice and associated with irregularities of the coronary vasculature. Administration of a vascular smooth muscle relaxant prevented onset of myocardial necrosis. Our data indicate that disruption of the SG-SSPN complex in vascular smooth muscle perturbs vascular function, which initiates cardiomyopathy and exacerbates muscular dystrophy

Frizzled-3a and slit2 genetically interact to modulate midline axon crossing in the telencephalon

The anterior commissure forms the first axon connections between the two sides of the embryonic telencephalon. We investigated the role of the transmembrane receptor Frizzled-3a in the development of this commissure using zebrafish as an experimental model. Knock down of Frizzled-3a resulted in complete loss of the anterior commissure. This defect was accompanied by a loss of the glial bridge, expansion of the slit2 expression domain and perturbation of the midline telencephalic-diencephalic boundary. Blocking Slit2 activity following knock down of Frizzled-3a effectively rescued the anterior commissure defect which suggested that Frizzled-3a was indirectly controlling the growth of axons across the rostral midline. We have shown here that Frizzled-3a is essential for normal development of the commissural plate and that loss-of-function causes Slit2-dependent defects in axon midline crossing in the embryonic vertebrate forebrain. These data supports a model whereby Wnt signaling through Frizzled-3a attenuates expression of Slit2 in the rostral midline of the forebrain. The absence of Slit2 facilitates the formation of a midline bridge of glial cells which is used as a substrate for commissural axons. In the absence of this platform of glia, commissural axons fail to cross the rostral midline of the forebrain. Crown copyright (C) 2012 Published by Elsevier Ireland Ltd. All rights reserved

Loss-of-function mutations in UDP-Glucose 6-Dehydrogenase cause recessive developmental epileptic encephalopathy

AbstractDevelopmental epileptic encephalopathies are devastating disorders characterized by intractable epileptic seizures and developmental delay. Here, we report an allelic series of germline recessive mutations in UGDH in 36 cases from 25 families presenting with epileptic encephalopathy with developmental delay and hypotonia. UGDH encodes an oxidoreductase that converts UDP-glucose to UDP-glucuronic acid, a key component of specific proteoglycans and glycolipids. Consistent with being loss-of-function alleles, we show using patients’ primary fibroblasts and biochemical assays, that these mutations either impair UGDH stability, oligomerization, or enzymatic activity. In vitro, patient-derived cerebral organoids are smaller with a reduced number of proliferating neuronal progenitors while mutant ugdh zebrafish do not phenocopy the human disease. Our study defines UGDH as a key player for the production of extracellular matrix components that are essential for human brain development. Based on the incidence of variants observed, UGDH mutations are likely to be a frequent cause of recessive epileptic encephalopathy.</jats:p

Loss-of-function mutations in UDP-Glucose 6-Dehydrogenase cause recessive developmental epileptic encephalopathy

Developmental epileptic encephalopathies are devastating disorders characterized by intractable epileptic seizures and developmental delay. Here, we report an allelic series of germline recessive mutations in UGDH in 36 cases from 25 families presenting with epileptic encephalopathy with developmental delay and hypotonia. UGDH encodes an oxidoreductase that converts UDP-glucose to UDP-glucuronic acid, a key component of specific proteoglycans and glycolipids. Consistent with being loss-of-function alleles, we show using patients’ primary fibroblasts and biochemical assays, that these mutations either impair UGDH stability, oligomerization, or enzymatic activity. In vitro, patient-derived cerebral organoids are smaller with a reduced number of proliferating neuronal progenitors while mutant ugdh zebrafish do not phenocopy the human disease. Our study defines UGDH as a key player for the production of extracellular matrix components that are essential for human brain development. Based on the incidence of variants observed, UGDH mutations are likely to be a frequent cause of recessive epileptic encephalopathy

Anxiety and Depression as Comorbid Factors in Drinking Behaviors of Undergraduate Students in an Urban Private University

This study examined differences among four drinking behavior groups (non-drinkers, low-risk drinkers, high-risk drinkers, and frequent high-risk drinkers) with respect to anxiety and depression in undergraduate males (n = 457) and females (n = 485). Participants completed a demographic questionnaire, the Alcohol Use Disorders Identification Test, the Beck Anxiety Inventory, and the Beck Depression Inventory. Results indicated significant differences among the groups only with respect to anxiety (F = 6.49, p \u3c .001), and in levels of anxiety (p \u3c .01) between high-risk females and males. Findings imply needed changes in prevention approaches to reduce high-risk drinking

Extranodal diffuse large B-cell lymphoma with monoclonal gammopathy: an aggressive and primary refractory disease responding to an immunomodulatory agent

Although the clinical outcome of patients with diffuse large B cell lymphoma (DLBCL) has been improved by the addition of rituximab to standard chemotherapy, almost one-third fails or relapses after first line treatment. The presence of monoclonal gammopathy (MG) is a known adverse prognostic factor for DLBCL. Because this subset of patients does not benefit from R-CHOP, new therapeutic options are required. Herein, we report the first case of extranodal DBCL of the lung with a concomitant MG who achieved a long lasting complete remission with lenalidomide