In Vitro Assembly of Neurospora Assimilatory Nitrate Reductase from Protein Subunits of a Neurospora Mutant and the Xanthine Oxidizing or Aldehyde Oxidase Systems of Higher Animals

In vitro assembly or complementation of a hybrid assimilatory nitrate reductase was attained by mixing a preparation of nitrate-induced N. crassa mutant nit-1 specifically with acid-treated (pH 2.5) bovine milk or intestinal xanthine oxidase, rabbit liver aldehyde oxidase, or chicken liver xanthine dehydrogenase. The complementation reaction specifically required induced nit-1, the only nitrate reductase mutant of Neurospora that lacked xanthine dehydrogenase and was unable to use hypoxathine or nitrate as a sole nitrogen source. The complementing activities of the above acid-treated enzymes correspond to their xanthine or aldehyde oxidizing activity profiles on sucrose density gradients. The resulting soluble, reduced nicotinamide adenine dinucleotide phosphate (NADPH)-nitrate reductases are the same as the Neurospora wild type enzyme in sucrose density gradient profile, molecular weight, substrate affinities, and sensitivity to inhibitors and temperature. By analogy to a similar in vitro complementation of nitrate reductase in mixtures of induced nit-1 and individual nonalleic Neurospora mutants, or uninduced wild type, the complemented nitrate apparently consists of an inducible protein subunit (possessing inducible NADPH-cytochrome c reductase) furnished by nit-1 and a subunit from the acid-treated xanthine or aldehyde oxidizing system which can substitute for the constitutive component furnished by the other mutants or uninduced wild type. The data suggest that Neurospora nitrate reductase and the xanthine oxidizing system and aldehyde oxidase of animals, all of which are molybdenum-containing enzymes catalyzing the reduction of nitrate to nitrite, share a highly similar protein subunit.     

Ministry of Health Clinical Practice Guidelines: Anxiety Disorders

The Ministry of Health (MOH) has developed the clinical practice guidelines on Anxiety Disorders to provide doctors and patients in Singapore with evidence-based treatment for anxiety disorders. This article reproduces the introduction and executive summary (with recommendations from the guidelines) from the MOH clinical practice guidelines on anxiety disorders, for the information of SMJ readers. Chapters and page numbers mentioned in the reproduced extract refer to the full text of the guidelines, which are available from the Ministry of Health website: http://www.moh.gov.sg/content/moh_web/healthprofessionalsportal/doctors/guidelines/cpg_medical.html. The recommendations should be used with reference to the full text of the guidelines. Following this article are multiple choice questions based on the full text of the guidelines.

1.1 Background information

Anxiety disorders are known to be one of the most prevalent of psychiatric conditions, yet they often remain under-diagnosed and under-treated. Their chronic, disabling symptoms cause considerable burden not only to sufferers but also to their families, and contribute to poorer quality of life and considerable economic burden on society.In many instances, there is a delay in seeking treatment and in some cases such delay may stretch up to nearly ten years. This may result from ignorance of the condition, fear of taking medications, and the stigma of receiving a psychiatric diagnosis, and or having to accept psychiatric treatment.The anxiety disorders include panic disorder with or without agoraphobia, social anxiety disorder, specific phobia, obsessive-compulsive disorder, generalised anxiety disorder, acute stress disorder and post-traumatic stress disorder. In the clinical evaluation of anxiety disorders, it is important to ascertain the type of anxiety disorder present. This would allow treatment to be targeted at the specific type of disorder.These guidelines are developed to provide practical, evidence-based recommendations to primary care physicians and specialists in psychiatry for the diagnosis and management of the anxiety disorders.The first edition of the guidelines was published in 2003. In this edition, we present data from newer research as well as older data not previously reported in the earlier guidelines.For example, we examine the efficacy of combining medications with psychological therapy over medications alone, or psychological therapy alone. In view of the majority of anxiety sufferers being female we have made recommendations for pharmacotherapy during pregnancy and breastfeeding. As these guidelines are intended for use in the Singapore context, we have omitted treatments that are currently not available in Singapore.

1.2 Aim

These guidelines are developed to facilitate the diagnosis and assessment of the anxiety disorders, and to ensure that their management is appropriate and effective.

1.3 Scope

These guidelines will cover the management of anxiety disorders in adults and address the issues of medication use during pregnancy and breastfeeding.

1.4 Target group

The content of the guidelines will be useful for all doctors treating patients with anxiety disorders. Efforts have been made to ensure that the guidelines are particularly useful for primary care physicians and specialists in psychiatry, including all those involved in the assessment and management of patients with anxiety disorders in the community. The doctor treating the patient is ultimately responsible for clinical decisions made after reviewing the individual patient’s history, clinical presentation and treatment options available.

1.5 Development of guidelines

These guidelines have been produced by a committee of psychiatrists, a clinical psychologist, pharmacist, patient representative, and family practitioners appointed by the Ministry of Health. They were developed by revising the existing guidelines, reviewing relevant literature, including overseas clinical practice guidelines, and by expert clinical consensus of professionals with experience in treating patients in the local setting.The following principles underlie the development of these guidelines:

• Treatment recommendations are supported by scientific evidence whenever possible (randomised controlled clinical trials represent the highest level of evidence) and expert clinical consensus is used when such data are lacking.
• Treatment should maximise therapeutic benefits and minimise side effects.

1.6 What’s new in the revised guidelines

This edition of the guidelines contains updated recommendations based on latest evidence, as well as detailed discussions and recommendations on the management of anxiety disorders in adult populations.The following represent changes to the revised guidelines

• An extensive review of the literature, including new evidence. This involved the re-writing and extensive revision of the chapters.
• Length of treatment, which provides answers to a pertinent question.
• Use of medications during pregnancy and breastfeeding. Given that females are more likely to be at risk of being diagnosed with anxiety disorders, this is an important subject.

We are aware that the Diagnostic and Statistical Manual of Mental Disorders-5 (DSM-5) was released in 2013. In DSM-5, post-traumatic stress disorder and obsessive-compulsive disorder have been removed and classified separately from the rest of the anxiety disorders. If we were to adhere strictly to DSM-5, this would entail omitting discussion on post-traumatic stress disorder and obsessive-compulsive disorder. As it is our aim to provide an update on the 2003 guidelines, post-traumatic stress disorder and obsessive-compulsive disorder have been included in this edition of the guidelines.In addition, anxiety conditions in children are included in DSM-5. Since the present guidelines are meant to address only adult anxiety disorders, guidelines on children’s anxiety conditions are not included here.Hence, for purposes of these guidelines, we will continue to use classifications based on the International Classification of Diseases-10 (ICD-10) and DSM-IV-TR criteria.

1.7 Review of guidelines

Evidence-based clinical practice guidelines are only as current as the evidence that supports them. Users must keep in mind that new evidence could supersede recommendations in these guidelines. The workgroup advises that these guidelines be scheduled for review five years after publication, or when new evidence appears that requires substantive changes to the present recommendations.     

Redox therapeutics in hepatic ischemia reperfusion injury

Ischemia-reperfusion plays a major role in the injury experienced by the liver during transplantation. Much work has been done recently investigating the role of redox species in hepatic ischemia-reperfusion. As animal models are better characterized and developed, and more insights are gained into the pathophysiology of hepatic ischemia reperfusion injury in humans the questions into exactly how oxidants participate in this injury are becoming more refined. These questions include effects of cellular location, timing of injury, and ability of therapeutics to access this site are increasing our appreciation of the complexity of ischemia reperfusion and improving attempts to ameliorate its effects. In this review, we aim to discuss the various methods to alter redox chemistry during ischemia reperfusion injury and future prospects for preventing organ injury during hepatic ischemia reperfusion.     

Relationships Between Eight Measures of Suspect Effort

Previous studies have recommended that multiple measures be employed concurrently to provide converging evidence regarding the presence of suspect effort during neuropsychological assessment. However, if the tests are highly correlated they do not represent independent sources of information. To date, no study has examined correspondence between effort tests. The present study assessed the relationships between eight measures which can be used to assess effort (Rey 15-item, Rey Dot Counting Test, Rey Word Recognition Test, RAVLT recognition trial, Rey-Osterrieth Complex Figure Test effort equation, Digit Span, Warrington Recognition Memory Test-Words, and “b” Test) in a sample of 105 patients in litigation or attempting to obtain/maintain disability compensation and who displayed noncredible symptoms based on psychometric performance and behavioral criteria. Modest to moderate correlations were observed between test summary scores with only two measures sharing more than 50% score variance (Digit Span and Dot Counting). Moderate correlations were also observed between individual test scores reflecting indices of response time, free recall, recognition, and false positive errors, providing possible evidence that patients may use specific strategies when producing noncredible performances. Overall the results suggest that the use of these various tests generally provides nonredundant data regarding patient credibility in neuropsychological evaluations.     

Scores on the MMPI-2-RF Scales as a Function of Increasing Levels of Failure on Cognitive Symptom Validity Tests in a Military Sample

This research examined associations between the full range of Minnesota Multiphasic Personality Inventory-2-Restructured Form (MMPI-2-RF) validity and substantive scales and increasing levels of cognitive symptom validity test (SVT) failure in a sample of 501 military members who completed a neuropsychological evaluation primarily for mild traumatic brain injury resulting from a closed head injury and blast exposure or heat injury. SVT failure was associated with significant linear increases in all of the over-reporting MMPI-2-RF validity scales and most of the substantive scales. For the validity scales, all over-reporting scales had large effect sizes (ESs) when comparing a group that failed no SVTs with a group that failed three SVTs. A comparison between these two groups for the substantive scales revealed the largest ESs for scales related to somatic/cognitive complaints and emotional dysfunction. RBS (Response Bias Scale) had the largest ES of all scales (d?=?1.69), followed by FBS-r (Symptom Validity Scale; d?=?1.34), AXY (Anxiety, d?=?1.21), and COG (Cognitive Complaints, d?=?1.19). The scales related to behavioral dysfunction had the smallest ESs of all of the substantive scales, and there were no significant associations between the vast majority of these scales and SVT failure. With respect to clinically significant elevations, those who did not fail SVTs had clinically significant elevations only on COG and NUC (Neurological Complaints), and MLS (Malaise) approached clinical significance. For those who failed SVTs, RBS was the only over-reporting scale that was elevated across all failure groups. Those who failed any SVT had clinically significant elevations on COG, MLS, NUC, and AXY. Those who failed three SVTs had additional elevations on scales related to emotional dysfunction.