Purification and properties of the malic enzyme and the malate dehydrogenases from the gill tissue of the ribbed mussel (Modiolus demissus)

To assess the role of dicarboxylic acid metabolism in the synthesis of alanine and other compounds by the ribbed mussel under conditions of hyperosmotic and anaerobic stress, the cytosolic and mitochondrial malate dehydrogenases and the mitochondrial malic enzyme from this organism were purified and their kinetics studied. Both the cytosolic and mitochondrial malate dehydrogenases were found to be dimers with native M[subscript] r = 60,000. One cMDH allele (designated slow) was found to predominate in populations from Cape Cod, MA. Similar low K[subscript] m\u27s were observed for purified preparations of the slow/slow homodimer (cMDH) and for the purified mitochondrial MDH (mMDH) for the substrates NAD and NADH under all experimental conditions. The mMDH had lower apparent K[subscript] m\u27s for oxaloacetate and higher apparent K[subscript] m\u27s for malate under all experimental conditions. Both forms exhibited substrate inhibition by oxaloacetate and malate with the mMDH more sensitive as assessed by the lower apparent K[subscript] i\u27s for these substrates. The mMDH was more sensitive to inhibition by sodium chloride, and lithium chloride than the cMDH. Alanine and sodium acetate were inhibitory to the cMDH, whereas the mitochondrial form was insensitive to inhibition by these compounds. The mMDH was more sensitive to inhibition by the malate analogue hydroxymalonate than the cMDH. The cMDH was more sensitive to inhibition by ATP than the mMDH. The mitochondrial malic enzyme (ME) had high affinity for metal ions. Mg[superscript]2+ (K[subscript]0.5 140 micromolar) and Co[superscript]2+ (K[subscript]0.5 2 picomolar) were able to restore only 60% of the Mn[superscript]2+ (K[subscript]0.5 18 picomolar) dependent activity. Only limited reactivity was found when NAD was substituted for NADP. Each of the several salts tested (sodium chloride, potassium chloride, lithium chloride, and sodium acetate), hydroxymalonate, and fumarate were inhibitory. Product inhibition patterns indicated that this enzyme operates according to a random reaction mechanism. This ME was a tetramer with native M[subscript] r 265,000. The co-localization of these activities with aspartate aminotransferase and the alanine aminotransferase may account for the appearance in alanine of aspartate derived label during hyperosmotic stress and anaerobic stress

Development of the Perinatal Depression Inventory (PDI)-14 using item response theory: a comparison of the BDI-II, EPDS, PDI, and PHQ-9

The objective of this study is to develop a simple, brief, self-report perinatal depression inventory that accurately measures severity in a number of populations. Our team developed 159 Likert-scale perinatal depression items using simple sentences with a fifth-grade reading level. Based on iterative cognitive interviewing (CI), an expert panel improved and winnowed the item pool based on pre-determined criteria. The resulting 67 items were administered to a sample of 628 pregnant and 251 postpartum women with different levels of depression at private and public sector obstetrics clinics, together with the Beck Depression Inventory (BDI-II), Edinburg Postpartum Depression Scale (EPDS), and the Patient Health Questionnaire (PHQ-9), as well as Module A of the Structured Clinical Interview for DSM-IV Diagnoses (SCID). Responses were evaluated using Item Response Theory (IRT). The Perinatal Depression Inventory (PDI)-14 items are highly informative regarding depression severity and function similarly and informatively across pregnant/postpartum, white/non-white, and private-clinic/public-clinic populations. PDI-14 scores correlate well with the PHQ-9, EPDS, and BDI-II, but the PDI-14 provides a more precise measure of severity using far fewer words. The PDI-14 is a brief depression assessment that excels at accurately measuring depression severity across a wide range of severity and perinatal populations.Electronic supplementary materialThe online version of this article (doi:10.1007/s00737-015-0553-9) contains supplementary material, which is available to authorized users

The Early Psychosis Screener (EPS): Quantitative validation against the SIPS using machine learning

Machine learning techniques were used to identify highly informative early psychosis self-report items and to validate an early psychosis screener (EPS) against the Structured Interview for Psychosis-risk Syndromes (SIPS). The Prodromal Questionnaire–Brief Version (PQ-B) and 148 additional items were administered to 229 individuals being screened with the SIPS at 7 North American Prodrome Longitudinal Study sites and at Columbia University. Fifty individuals were found to have SIPS scores of 0, 1, or 2, making them clinically low risk (CLR) controls; 144 were classified as clinically high risk (CHR) (SIPS 3–5) and 35 were found to have first episode psychosis (FEP) (SIPS 6). Spectral clustering analysis, performed on 124 of the items, yielded two cohesive item groups, the first mostly related to psychosis and mania, the second mostly related to depression, anxiety, and social and general work/school functioning. Items within each group were sorted according to their usefulness in distinguishing between CLR and CHR individuals using the Minimum Redundancy Maximum Relevance procedure. A receiver operating characteristic area under the curve (AUC) analysis indicated that maximal differentiation of CLR and CHR participants was achieved with a 26-item solution (AUC = 0.899 ± 0.001). The EPS-26 outperformed the PQ-B (AUC = 0.834 ± 0.001). For screening purposes, the self-report EPS-26 appeared to differentiate individuals who are either CLR or CHR approximately as well as the clinician-administered SIPS. The EPS-26 may prove useful as a self-report screener and may lead to a decrease in the duration of untreated psychosis. A validation of the EPS-26 against actual conversion is underway

The Early Psychosis Screener (EPS): Item development and qualitative validation

A panel of experts assembled and analyzed a comprehensive item bank from which a highly sensitive and specific early psychosis screener could be developed. Twenty well-established assessments relating to the prodromal stage, early psychosis, and psychosis were identified. Using DSM-5 criteria, we identified the core concepts represented by each of the items in each of the assessments. These granular core concepts were converted into a uniform set of 490 self-report items using a Likert scale and a ‘past 30 days’ time frame. Partial redundancy was allowed to assure adequate concept coverage. A panel of experts and TeleSage staff rated these items and eliminated 189 items, resulting in 301 items. The items were subjected to five rounds of cognitive interviewing with 16 individuals at clinically high risk for psychosis and 26 community mental health center patients. After each round, the expert panel iteratively reviewed, rated, revised, added, or deleted items to maximize clarity and centrality to the concept. As a result of the interviews, 36 items were revised, 52 items were added, and 205 items were deleted. By the last round of cognitive interviewing, all of the items were clearly understood by all participants. In future work, responses to the final set of 148 items and machine learning techniques will be used to quantitatively identify the subset of items that will best predict clinical high-risk status and conversion

The Early Psychosis Screener for Internet (EPSI)-SR: Predicting 12 month psychotic conversion using machine learning

Introduction: A faster and more accurate self-report screener for early psychosis is needed to promote early identification and intervention. Methods: Self-report Likert-scale survey items were administered to individuals being screened with the Structured Interview for Psychosis-risk Syndromes (SIPS) and followed at eight early psychosis clinics. An a priori analytic plan included Spectral Clustering Analysis to reduce the item pool, followed by development of Support Vector Machine (SVM) classifiers. Results: The cross-validated positive predictive value (PPV) of the EPSI at the default cut-off (76.5%) exceeded that of the clinician-administered SIPS (68.5%) at separating individuals who would not convert to psychosis within 12 months from those who either would convert within 12 months or who had already experienced a first episode psychosis (FEP). When used in tandem with the SIPS on clinical high risk participants, the EPSI increased the combined PPV to 86.6%. The SVM classified as FEP/converters only 1% of individuals in non-clinical and 4% of clinical low risk populations. Sensitivity of the EPSI, however, was 51% at the default cut-off. Discussion: The EPSI identifies, comparably to the SIPS but in less time and with fewer resources, individuals who are either at very high risk to develop a psychotic disorder within 12 months or who are already psychotic. At its default cut-off, EPSI misses 49% of current or future psychotic cases. The cut-off can, however, be adjusted based on purpose. The EPSI is the first validated assessment to predict 12-month psychotic conversion. An online screening system, www.eps.telesage.org, is under development

Can we continue research in splenectomized dogs? Mycoplasma haemocanis: Old problem - New insight

We report the appearance of a Mycoplasma haemocanis infection in laboratory dogs, which has been reported previously, yet, never before in Europe. Outbreak of the disease was triggered by a splenectomy intended to prepare the dogs for a hemorrhagic shock study. The clinical course of the dogs was dramatic including anorexia and hemolytic anemia. Treatment included allogeneic transfusion, prednisone, and oxytetracycline. Systematic follow-up (n=12, blood smears, antibody testing and specific polymerase chain reaction) gives clear evidence that persistent eradication of M. haemocanis is unlikely. We, therefore, had to abandon the intended shock study. In the absence of effective surveillance and screening for M. haemocanis, the question arises whether it is prudent to continue shock research in splenectomized dogs. Copyright (C) 2004 S. Karger AG, Basel