Bio

Clinical Focus


  • Psychiatry

Academic Appointments


  • Clinical Assistant Professor, Psychiatry and Behavioral Sciences

Professional Education


  • Board Certification: Psychiatry, American Board of Psychiatry and Neurology (2012)
  • Medical Education:Washington University in St Louis (2007) MO
  • Fellowship:Stanford University - Dept of Psychiatry (2012) CA
  • Residency:Stanford University - Dept of Psychiatry (2011) CA

Research & Scholarship

Clinical Trials


  • Valproic Acid for Treatment of Hyperactive or Mixed Delirium in ICU Recruiting

    Delirium is the most often encountered psychiatric diagnosis in the general hospital, with incidence up to 85% in the intensive care unit (ICU) setting and with significant consequences on patients' morbidity and mortality. Currently, although not FDA approved, antipsychotics are often considered the first-line pharmacological treatment. However, there can be limitations to their use, including side effects or lack of efficacy. Valproic acid (VPA) is one of the alternatives at times used in such patients which from limited case series data appears to be helpful and tolerated. VPA can provide relief from agitation that poses a threat to the safety and recovery of the patient. Moreover, mechanistically it addresses the neurochemical and cellular abnormalities inherent in delirium (it has NMDA-antagonist, anti-dopaminergic, GABAergic,anti-inflammatory, anti-apoptotic, and histone deacetylase inhibitor properties, among others). The purpose of this study is to evaluate the efficacy and tolerability of the VPA in the first known to us randomized controlled trial.

    View full details

Publications

Journal Articles


  • An Insatiable Desire for Tofu: A Case of Restless Legs and Unusual Pica in Iron Deficiency Anemia PSYCHOSOMATICS Sher, Y., Maldonado, J. R. 2014; 55 (6): 680-685

    View details for Web of Science ID 000346182000019

    View details for PubMedID 25497506

  • The "Prediction of Alcohol Withdrawal Severity Scale" (PAWSS): Systematic literature review and pilot study of a new scale for the prediction of complicated alcohol withdrawal syndrome ALCOHOL Maldonado, J. R., Sher, Y., Ashouri, J. F., Hills-Evans, K., Swendsen, H., Lolak, S., Miller, A. C. 2014; 48 (4): 375-390

    Abstract

    To date, no screening tools for alcohol withdrawal syndromes (AWS) have been validated in the medically ill. Although several tools quantify the severity of AWS (e.g., Clinical Institute Withdrawal Assessment for Alcohol [CIWA]), none identify subjects at risk of AWS, thus missing the opportunity for timely prophylaxis. Moreover, there are no validated tools for the prediction of complicated (i.e., moderate to severe) AWS in the medically ill.Our goals were (1) to conduct a systematic review of the published literature on AWS to identify clinical factors associated with the development of AWS, (2) to use the identified factors to develop a tool for the prediction of alcohol withdrawal among patients at risk, and (3) to conduct a pilot study to assess the validity of the tool.For the creation of the Prediction of Alcohol Withdrawal Severity Scale (PAWSS), we conducted a systematic literature search using PRISMA (preferred reporting items for systematic reviews and meta-analyses) guidelines for clinical factors associated with the development of AWS, using PubMed, PsychInfo, MEDLINE, and Cochrane Databases. Eligibility criteria included: (i) manuscripts dealing with human subjects, age 18 years or older, (ii) manuscripts directly addressing descriptions of AWS or its predisposing factors, including case reports, naturalistic case descriptions, and all types of clinical trials (e.g., randomized, single-blind, or open label studies), (iii) manuscripts describing characteristics of alcohol use disorder (AUD), and (iv) manuscripts dealing with animal data (which were considered only if they directly dealt with variables described in humans). Obtained data were used to develop the Prediction of Alcohol Withdrawal Severity Scale, in order to assist in the identification of patients at risk for complicated AWS. A pilot study was conducted to assess the new tool's psychometric qualities on patients admitted to a general inpatient medicine unit over a 2-week period, who agreed to participate in the study. Blind to PAWSS results, a separate group of researchers retrospectively examined the medical records for evidence of AWS.The search produced 2802 articles describing factors potentially associated with increased risk for AWS, increased severity of withdrawal symptoms, and potential characteristics differentiating subjects with various forms of AWS. Of these, 446 articles met inclusion criteria and underwent further scrutiny, yielding a total of 233 unique articles describing factors predictive of AWS. A total of 10 items were identified as correlated with complicated AWS (i.e., withdrawal hallucinosis, withdrawal-related seizures, and delirium tremens) and used to construct the PAWSS. During the pilot study, a total of 68 subjects underwent evaluation with PAWSS. In this pilot sample the sensitivity, specificity, and positive and negative predictive values of PAWSS were 100%, using the threshold score of 4.The results of the literature search identified 10 items which may be correlated with risk for complicated AWS. These items were assembled into a tool to assist in the identification of patients at risk: PAWSS. The results of this pilot study suggest that PAWSS may be useful in identifying risk of complicated AWS in medically ill, hospitalized individuals. PAWSS is the first validated tool for the prediction of severe AWS in the medically ill and its use may aid in the early identification of patients at risk for complicated AWS, allowing for prophylaxis against AWS before severe alcohol withdrawal syndromes develop.

    View details for DOI 10.1016/j.alcohol.2014.01.004

    View details for Web of Science ID 000337071100007

    View details for PubMedID 24657098

  • The Stanford Integrated Psychosocial Assessment for Transplantation (SIPAT): A New Tool for the Psychosocial Evaluation of Pre-Transplant Candidates PSYCHOSOMATICS Maldonado, J. R., Dubois, H. C., David, E. E., Sher, Y., Lolak, S., Dyal, J., Witten, D. 2012; 53 (2): 123-132

    Abstract

    While medical criteria have been well established for each end-organ system, psychosocial listing criteria are less standardized. To address this limitation, we developed and tested a new assessment tool: the Stanford Integrated Psychosocial Assessment for Transplantation (SIPAT).The SIPAT was developed from a comprehensive review of the literature on the psychosocial factors that impact transplant outcomes. Five examiners blindly applied the SIPAT to 102 randomly selected transplant cases, including liver, heart, and lung patients. After all subject's files had been rated by the examiners, the respective transplant teams provided the research team with the patient's outcome data.Univariate logistic regression models were fit in order to predict the transplant psychosocial outcome (positive or negative) using each rater's SIPAT scores. These results show that SIPAT scores are highly predictive of the transplant psychosocial outcome (P < 0.0001). The instrument has excellent inter-rater reliability (Pearson's correlation coefficient = 0.853), even among novice raters.The SIPAT is a comprehensive screening tool to assist in the psychosocial assessment of organ transplant candidates. Its strengths includes the standardization of the evaluation process and its ability to identify subjects who are at risk for negative outcomes after the transplant, in order to allow for the development of interventions directed at improving the patient's candidacy. Our goal is that the SIPAT, in addition to a set of agreed upon minimal psychosocial listing criteria, would be used in combination with organ-specific medical listing criteria in order to establish standardized criteria for the selection of transplant recipients.

    View details for Web of Science ID 000301998100003

    View details for PubMedID 22424160

  • The Impact of Depression in Heart Disease CURRENT PSYCHIATRY REPORTS Sher, Y., Lolak, S., Maldonado, J. R. 2010; 12 (3): 255-264

    Abstract

    Depression and heart disease affect millions of people worldwide. Studies have shown that depression is a significant risk factor for new heart disease and that it increases morbidity and mortality in established heart disease. Many hypothesized and studied mechanisms have linked depression and heart disease, including serotonergic pathway and platelet dysfunction, inflammation, autonomic nervous system and hypothalamic-pituitary-adrenal axis imbalance, and psychosocial factors. Although the treatment of depression in cardiac patients has been shown to be safe and modestly efficacious, it has yet to translate into reduced cardiovascular morbidity and mortality. Understanding the impact and mechanisms behind the association of depression and heart disease may allow for the development of treatments aimed at altering the devastating consequences caused by these comorbid illnesses.

    View details for DOI 10.1007/s11920-010-0116-8

    View details for Web of Science ID 000289731700015

    View details for PubMedID 20425289

  • Differences in protonation of ubiquinone and menaquinone in fumarate reductase from Escherichia coli JOURNAL OF BIOLOGICAL CHEMISTRY Maklashina, E., Hellwig, P., Rothery, R. A., Kotlyar, V., Sher, Y., Weiner, J. H., Cecchini, G. 2006; 281 (36): 26655-26664

    Abstract

    Escherichia coli quinol-fumarate reductase operates with both natural quinones, ubiquinone (UQ) and menaquinone (MQ), at a single quinone binding site. We have utilized a combination of mutagenesis, kinetic, EPR, and Fourier transform infrared methods to study the role of two residues, Lys-B228 and Glu-C29, at the quinol-fumarate reductase quinone binding site in reactions with MQ and UQ. The data demonstrate that Lys-B228 provides a strong hydrogen bond to MQ and is essential for reactions with both quinone types. Substitution of Glu-C29 with Leu and Phe caused a dramatic decrease in enzymatic reactions with MQ in agreement with previous studies, however, the succinate-UQ reductase reaction remains unaffected. Elimination of a negative charge in Glu-C29 mutant enzymes resulted in significantly increased stabilization of both UQ-* and MQ-* semiquinones. The data presented here suggest similar hydrogen bonding of the C1 carbonyl of both MQ and UQ, whereas there is different hydrogen bonding for their C4 carbonyls. The differences are shown by a single point mutation of Glu-C29, which transforms the enzyme from one that is predominantly a menaquinol-fumarate reductase to one that is essentially only functional as a succinate-ubiquinone reductase. These findings represent an example of how enzymes that are designed to accommodate either UQ or MQ at a single Q binding site may nevertheless develop sufficient plasticity at the binding pocket to react differently with MQ and UQ.

    View details for DOI 10.1074/jbc.M602938200

    View details for Web of Science ID 000240249500083

    View details for PubMedID 16829675

  • Fumarate reductase and succinate oxidase activity of Escherichia coli complex II homologs are perturbed differently by mutation of the flavin binding domain JOURNAL OF BIOLOGICAL CHEMISTRY Maklashina, E., Iverson, T. M., Sher, Y., Kotlyar, V., Andrell, J., Mirza, O., Hudson, J. M., Armstrong, F. A., Rothery, R. A., Weiner, J. H., Cecchini, G. 2006; 281 (16): 11357-11365

    Abstract

    The Escherichia coli complex II homologues succinate:ubiquinone oxidoreductase (SQR, SdhCDAB) and menaquinol:fumarate oxidoreductase (QFR, FrdABCD) have remarkable structural homology at their dicarboxylate binding sites. Although both SQR and QFR can catalyze the interconversion of fumarate and succinate, QFR is a much better fumarate reductase, and SQR is a better succinate oxidase. An exception to the conservation of amino acids near the dicarboxylate binding sites of the two enzymes is that there is a Glu (FrdA Glu-49) near the covalently bound FAD cofactor in most QFRs, which is replaced with a Gln (SdhA Gln-50) in SQRs. The role of the amino acid side chain in enzymes with Glu/Gln/Ala substitutions at FrdA Glu-49 and SdhA Gln-50 has been investigated in this study. The data demonstrate that the mutant enzymes with Ala substitutions in either QFR or SQR remain functionally similar to their wild type counterparts. There were, however, dramatic changes in the catalytic properties when Glu and Gln were exchanged for each other in QFR and SQR. The data show that QFR and SQR enzymes are more efficient succinate oxidases when Gln is in the target position and a better fumarate reductase when Glu is present. Overall, structural and catalytic analyses of the FrdA E49Q and SdhA Q50E mutants suggest that coulombic effects and the electronic state of the FAD are critical in dictating the preferred directionality of the succinate/fumarate interconversions catalyzed by the complex II superfamily.

    View details for DOI 10.1074/jbc.M512544200

    View details for Web of Science ID 000236822200078

    View details for PubMedID 16484232

  • Electron transfer and catalytic control by the iron-sulfur clusters in a respiratory enzyme, E. coli fumarate reductase JOURNAL OF THE AMERICAN CHEMICAL SOCIETY Hudson, J. M., Heffron, K., Kotlyar, V., Sher, Y., Maklashina, E., Cecchini, G., Armstrong, F. A. 2005; 127 (19): 6977-6989

    Abstract

    Factors governing the efficacy of long-range electron relays in enzymes have been examined using protein film voltammetry in conjunction with site-directed mutagenesis. Investigations of the fumarate reductase from Escherichia coli, in which three Fe-S clusters relay electrons over more than 30 A, lead to the conclusion that varying the medial [4Fe-4S] cluster potential over a 100 mV range does not have a significant effect on the inherent kinetics of electron transfer to and from the active-site flavin. The results support a proposal that the reduction potential of an individual electron relay site in a multicentered enzyme is not a strong determinant of activity; instead, as deduced from the potential dependence of catalytic electron transfer, electron flow through the intramolecular relay is rapid and reversible, and even uphill steps do not limit the catalytic rate.

    View details for DOI 10.1021/ja043404q

    View details for Web of Science ID 000229085200032

    View details for PubMedID 15884941

  • Effect of anoxia/reperfusion on the reversible active/de-active transition of NADH-ubiquinone oxidoreductase (complex I) in rat heart BIOCHIMICA ET BIOPHYSICA ACTA-BIOENERGETICS Maklashina, E., Sher, Y., Zhou, H. Z., Gray, M. O., Karliner, J. S., Cecchini, G. 2002; 1556 (1): 6-12

    Abstract

    The multi-subunit mammalian NADH-ubiquinone oxidoreductase (complex I) is part of the mitochondrial electron transport chain and physiologically serves to reduce ubiquinone with NADH as the electron donor. The three-dimensional structure of this enzyme complex remains to be elucidated and also little is known about the physiological regulation of complex I. The enzyme complex in vitro is known to exist as a mixture of active (A) and de-active (D) forms [Biochim. Biophys. Acta 1364 (1998) 169]. Studies are reported here examining the effect of anoxia and reperfusion on the A/D-equilibrium of complex I in rat hearts ex vivo. Complex I from the freshly isolated rat heart or after prolonged (1 h) normoxic perfusion exists in almost fully active form (87+/-2%). Either 30 min of nitrogen perfusion or global ischemia decreases the portion of active form of complex I to 40+/-2%. Upon re-oxygenation of cardiac tissue, complex I is converted back predominantly to the active form (80-85%). Abrupt alternation of anoxic and normoxic perfusion allows cycling between the two states of the enzyme. The possible role in the physiological regulation of complex I activity is discussed.

    View details for Web of Science ID 000178384600002

    View details for PubMedID 12351213

Stanford Medicine Resources: