A structural interpretation of the acidity of groups associated with the hemes of hemoglobin and hemoglobin derivatives

Since the discovery by Bohr and coworkers in 1904 of the effect of acidity on the oxygen equilibrium of hemoglobin, there have been a large number of investigations directed towards clarification of the physicochemical relationships of acid groups with the hemes in hemoglobin and its derivatives. It is the purpose of this paper to analyze modern quantitative data, including those for ferrihemoglobin (methemoglobin), in order to throw new light on the general problem, to establish the ionization constant of an acid group in ferrihemoglobin previously unrecognized, and to give a structural interpretation of shifts in the pK of groups caused by changing chemical environment

Who are we becoming? A critical, communicative, reflective, transformative, timely inquiry into the coming-to-be of adult education in the early 21st century

The perspectives included in this collaborative document reflect the authors‘ initial inquiry to explore who are we becoming as adult educators. We present five unique points of view that our role as adult educators holds potential to help adults seek ways into their own deep inquiries of what are true, beautiful, and just ways of life. Our inquiries give expression to how might we create conditions for truth, beauty, and justice to emerge in our communities, in the systems that we work in, that govern us and that make way for our individual collective humanity? The time is ripe to ask what are the diverse structures, systems and expressions of an evolving humanity where justice, grace, beauty and truth take new shapes to meet unseen demands placed on adults around the world and what role adult education will play

Do risk factors for suicidal behavior differ by affective disorder polarity?

BACKGROUND: Suicide is a leading cause of death and has been strongly associated with affective disorders. The influence of affective disorder polarity on subsequent suicide attempts or completions and any differential effect of suicide risk factors by polarity were assessed in a prospective cohort. METHODS: Participants with major affective disorders in the National Institute of Mental Health Collaborative Depression Study were followed prospectively for up to twenty-five years. A total of 909 participants meeting prospective diagnostic criteria for major depressive and bipolar disorders were followed through 4,204 mood cycles. Suicidal behavior was defined as suicide attempts or completions. Mixed-effects, grouped-time survival analysis assessed risk of suicidal behavior and differential effects of risk factors for suicidal behavior by polarity. In addition to polarity, the main effects of age, gender, hopelessness, married status, prior suicide attempts, and active substance abuse were modeled with mood cycle as the unit of analysis. RESULTS: After controlling for age of onset, there were no differences in prior suicide attempts by polarity though bipolar participants had more prior severe attempts. During follow-up, forty cycles ended in suicide and 384 cycles contained at least one suicide attempt. Age, hopelessness, and active substance abuse but not polarity predicted suicidal behavior. The effects of risk factors did not differ by polarity. CONCLUSIONS: Bipolarity does not independently influence risk of suicidal behavior or the influence of well-established suicide risk factors within affective disorders. Suicide risk assessment strategies may continue to appraise these common risk factors without regard to mood polarity

Factors Associated with the Prescribing of Olanzapine, Quetiapine, and Risperidone in Patients with Bipolar and Related Affective Disorders

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/90038/1/phco.31.8.806.pd

Identification and characterization of 3.8 min 134mI

The [gamma]-ray spectra of iodine fractions rapidly separated from the products of slow neutron fission of 235U were studied. A 3.8 +/- 0.2 min species was found and was identified as 134mI from observations of corresponding growth in the intensities of the prominent 847 and 884 keV [gamma]-rays of 53 min 134I. This isomer is analogous to the 2.9 h isomer 134mCs and decays by the sequence 134mI (J[pi] = 8-)(J[pi] = 5+)134I (J[pi] = 4+) by transitions of and 44.4 +/- 0.1 keV(), respectively. For a 316 keV cross-over [gamma]-ray an upper limit of 1 % was obtained, and is near the intensity predicted by M4 systematics. A low-intensity [gamma]-ray of 234.3 +/- 0.5 keV was found This [gamma]-ray is interpreted as evidence for [beta]-decay (2%) of the isomer, possibly to the 0.29 sec 7- isomeric level in 134Xe.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/34159/1/0000445.pd

Aggressive Course in Encephalitis With Opsoclonus, Ataxia, Chorea, and Seizures. The First Pediatric Case of γ-Aminobutyric Acid Type B Receptor Autoimmunity

IMPORTANCE: Autoantibodies to the γ-aminobutyric acid type B (GABAB) receptor have recently been identified as a cause of autoimmune encephalitis. Most patients with GABAB encephalitis have presented with limbic encephalitis. About half of the cases reported have been paraneoplastic in origin, with the majority of tumors representing small cell lung cancer. OBSERVATIONS: We describe a 3-year-old boy who presented with a mixed movement disorder (opsoclonus, ataxia, and chorea) as well as seizures refractory to treatment. His seizures required continuous pentobarbital sodium infusion to be controlled. Despite treatment with intravenous corticosteroids and immunoglobulins, the patient ultimately died of overwhelming sepsis. CONCLUSIONS AND RELEVANCE: To our knowledge, this report represents the first pediatric case of GABAB-associated encephalitis. Our patient presented with encephalopathy, refractory seizures, and a mixed movement disorder rather than limbic encephalitis. γ-Aminobutyric acid type B receptor autoimmunity deserves consideration in pediatric patients presenting with encephalitis. Immune-mediated encephalitis with autoantibodies directed against synaptic proteins has become an important component of the differential diagnosis of patients with encephalitis. Current estimates suggest that a substantial proportion of patients once suspected to have viral encephalitis in fact have an autoimmune etiology for their symptoms.1 Additional autoantigen targets continue to be identified, and the phenotypic spectrum associated with autoimmune encephalitis continues to expand. We describe a 3-year-old patient who presented with acute-onset confusion, opsoclonus, chorea, and intractable seizures. Neuroimaging disclosed involvement of the brainstem, basal ganglia, and hippocampi. γ-Aminobutyric acid type B (GABAB) receptor autoantibodies were identified in the serum and cerebrospinal fluid (CSF). Despite immunomodulating therapy, the patient died of overwhelming sepsis. To our knowledge, this is the first description of a pediatric patient with GABAB receptor autoantibodies. The presence of opsoclonus, ataxia, and chorea expands the clinical phenotype and indicates that GABAB receptor autoimmunity should be considered in cases of pediatric encephaliti

Can We Really Prevent Suicide?

Every year, suicide is among the top 20 leading causes of death globally for all ages. Unfortunately, suicide is difficult to prevent, in large part because the prevalence of risk factors is high among the general population. In this review, clinical and psychological risk factors are examined and methods for suicide prevention are discussed. Prevention strategies found to be effective in suicide prevention include means restriction, responsible media coverage, and general public education, as well identification methods such as screening, gatekeeper training, and primary care physician education. Although the treatment for preventing suicide is difficult, follow-up that includes pharmacotherapy, psychotherapy, or both may be useful. However, prevention methods cannot be restricted to the individual. Community, social, and policy interventions will also be essentia

Genome-wide association study identifies 30 loci associated with bipolar disorder.

Bipolar disorder is a highly heritable psychiatric disorder. We performed a genome-wide association study (GWAS) including 20,352 cases and 31,358 controls of European descent, with follow-up analysis of 822 variants with P < 1 × 10-4 in an additional 9,412 cases and 137,760 controls. Eight of the 19 variants that were genome-wide significant (P < 5 × 10-8) in the discovery GWAS were not genome-wide significant in the combined analysis, consistent with small effect sizes and limited power but also with genetic heterogeneity. In the combined analysis, 30 loci were genome-wide significant, including 20 newly identified loci. The significant loci contain genes encoding ion channels, neurotransmitter transporters and synaptic components. Pathway analysis revealed nine significantly enriched gene sets, including regulation of insulin secretion and endocannabinoid signaling. Bipolar I disorder is strongly genetically correlated with schizophrenia, driven by psychosis, whereas bipolar II disorder is more strongly correlated with major depressive disorder. These findings address key clinical questions and provide potential biological mechanisms for bipolar disorder

Response to treatment in a prospective national infantile spasms cohort

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/134499/1/ana24594.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/134499/2/ana24594_am.pd