HIF-1 and HIF-2: working alone or together in hypoxia?

Erythropoietin (EPO) is the hormonal regulator of red cell production and provided the paradigm for oxygen-regulated gene expression that led to the discovery of hypoxia-inducible factor (HIF). In this issue of the JCI, Rankin and colleagues show, using targeted gene inactivation, that induction of Epo expression in murine liver is dependent on the integrity of HIF-2alpha, and not HIF-1alpha (see the related article beginning on page 1068). These results demonstrate distinct functions for different HIF-alpha isoforms that could potentially be exploited in therapeutic approaches to anemia.     

Policies and procedures: friend or foe? Part 2

Review a case where policy and procedure breaches resulted in disaster. Test your knowledge with the following questions, then check your answers at http://www.nursingmanagement.com.     

Policies and procedures: friend or foe? Part 1

Policy and procedure wording can make or break caregiving accountability. Test your knowledge with the following questions, then check your answers at http://www.nursingmanagement.com.     

Cognitive Biases in Childhood Anxiety, Depression, and Aggression: Are They Pervasive or Specific?

This study investigated the extent to which children’s negative information processing biases are pervasive across the cognitive modalities of attention, judgment, and memory and, further, whether such biases are specifically associated with anxiety, depression, and/or aggression. 133 children between the ages of 8 and 14 years were assessed on an attention allocation task, a vignette interpretation measure, and a memory recall task. Children also completed anxiety and depression inventories, and were rated by teachers on a measure of aggression. Overall the results suggested a predominantly pervasive negative bias associated with childhood psychopathology, with some evidence of specificity. The canonical correlation analyses indicated that high levels of anxiety, depression, and aggression were associated with biases: attention to negative information, interpretation of ambiguous situations as negative, and preferential recall of negative words. Above this general bias, anxiety displayed a specific association with attention to negative information in the univariate analyses.

The Cognitive and Emotional Phenomenology of Depression and Anxiety: Are Worry and Hopelessness the Cognitive Correlates of NA and PA?

The study attempted to integrate the cognitive content-specificity and tripartite literatures to create a more holistic model of the emotional, physiological, and cognitive phenomenology of depression and anxiety. In addition, the constructs of hopelessness and worry were used to clarify ambiguous findings in the cognitive content-specificity research and to identify possible cognitive correlates of high NA and low PA. The results from 124 clients at a university counseling center supported this attempt at integrating these literatures. Overall, there was good evidence that worry is a cognitive correlate of high NA. Consequently, we view worry and high NA as features of a constellation of correlated indices that are shared with both depressed and anxious mood states. Alternatively, the results also support the position that hopelessness is a cognitive correlate of low PA. These features—low PA and hopelessness—define correlated indices that help discriminate depressed from anxious states. We view this integration of the cognitive and emotional literatures as providing evidence for a comprehensive map of the emotional and cognitive phenomenology in depression and anxiety.     

Are 1 or 2 dangerous? Clozapine and olanzapine exposure in toddlers

Clozapine (Clozaril) and olanzapine (Zyprexa) are two relatively new atypical antipsychotics that are structurally and pharmacologically related. There are currently no therapeutic indications for these pharmaceuticals in infants and toddlers.Presumably, as the usage of these medications in adults increases, the frequency of unintentional pediatric ingestions will increase. In 2001 the annual report of the American Association of Poison Control Centers Toxic Exposure Surveillance System included a separate subcategory for atypical antipsychotics under the heading of sedatives/hypnotics/antipsychotics. The toxidrome resulting from these drugs is predominately central nervous system depression and anticholinergic effects. Although the desirable lack of extrapyramidal symptoms in adults results in their greatest clinical utility, several reports of toxic ingestions in small children are noteworthy for having extrapyramidal manifestations. We review here the available reported clinical experience with toxic doses of these medications that in small children may amount to as little as a single tablet. Although such doses may be lethal, supportive care and gastrointestinal decontamination in this population will generally lead to a good outcome.     

Islet amyloid and type 2 diabetes: overproduction or inadequate clearance and detoxification?

A hallmark of type 2 diabetes is the reduction of pancreatic islet β cell mass through induction of apoptosis and lack of regeneration. In most patients, β cell dysfunction is associated with the presence of extracellular amyloid plaques adjacent to β cells and intracellular toxic oligomers that are comprised of islet amyloid polypeptide (IAPP). In this issue of the JCI, three independent research groups reveal that a functional autophagy system normally prevents the accumulation of toxic IAPP oligomers in human IAPP–expressing murine models. Furthermore, mice expressing human IAPP but deficient for β cell autophagy through genetic deletion of the autophagy initiator ATG7 developed β cell apoptosis and overt diabetes. Together, these studies indicate that autophagy protects β cells from the accumulation of toxic IAPP oligomers and suggest that enhancing autophagy may be a novel target for prevention of type 2 diabetes.     

Cognitive status and ambulation in geriatric rehabilitation: walking without thinking?

OBJECTIVE: To assess the relation between cognitive and ambulatory abilities in geriatric rehabilitation inpatients. STUDY DESIGN: Survey study of geriatric cohorts. SETTING: Inpatient university hospital rehabilitation unit. PATIENTS: One hundred fifty urban geriatric rehabilitation patients with orthopedic, neurologic, or medical diagnoses. MAIN OUTCOME MEASURES: Functional Independence Measure (FIM), Mattis Dementia Rating Scale, Neurobehavioral Cognitive Status Examination. RESULTS: Both cognitive measures predicted admission and discharge total FIM scores, continence status, and activities of daily living (ADL) scores. Neither measure could predict admission or discharge FIM ambulation scores better than demographic variables. CONCLUSION: While cognitive status affects the overall rehabilitation course and ultimate functional status of the geriatric patient, it does not predict walking or stair climbing ability.     

Cognitive Behavioral Therapy in Adults with Obsessive–Compulsive Disorder and Borderline Intellectual Functioning: A Case Series of Three Patients

Cognitive-behavior therapy (CBT) is widely accepted as the most effective psychological treatment for obsessive–compulsive disorder (OCD). Although this modality flexibly treats a variety of OCD symptom subtypes, it is unclear how CBT should be adapted to meet the needs of individuals with OCD and limitations in their cognitive functioning. In this paper, we report on three adults with borderline intellectual functioning who received CBT following a protocol that was adapted to meet their unique developmental and intellectual needs. For the purposes of this case study, the following modifications were made to a standard treatment CBT protocol: 1) increased parental involvement, 2) simplified language, 3) decreased reliance on cognitive techniques, and 4) the addition of contingency management strategies and role modeling by caregivers. All three adult patients benefited from treatment as evidenced by significant reductions in their OCD symptoms at post-treatment. Conclusions from these cases are drawn, as well as directions for future research.