Can we distinguish respiratory viral infections based on clinical features? A prospective pediatric cohort compared to systematic literature review

Studies have shown that the predictive value of “clinical diagnoses” of influenza and other respiratory viral infections is low, especially in children. In routine care, pediatricians often resort to clinical diagnoses, even in the absence of robust evidence‐based criteria. We used a dual approach to identify clinical characteristics that may help to differentiate infections with common pathogens including influenza, respiratory syncytial virus, adenovirus, metapneumovirus, rhinovirus, bocavirus‐1, coronaviruses, or parainfluenza virus: (a) systematic review and meta‐analysis of 47 clinical studies published in Medline (June 1996 to March 2017, PROSPERO registration number: CRD42017059557) comprising 49 858 individuals and (b) data‐driven analysis of an inception cohort of 6073 children with ILI (aged 0‐18 years, 56% male, December 2009 to March 2015) examined at the point of care in addition to blinded PCR testing. We determined pooled odds ratios for the literature analysis and compared these to odds ratios based on the clinical cohort dataset. This combined analysis suggested significant associations between influenza and fever or headache, as well as between respiratory syncytial virus infection and cough, dyspnea, and wheezing. Similarly, literature and cohort data agreed on significant associations between HMPV infection and cough, as well as adenovirus infection and fever. Importantly, none of the abovementioned features were unique to any particular pathogen but were also observed in association with other respiratory viruses. In summary, our “real‐world” dataset confirmed published literature trends, but no individual feature allows any particular type of viral infection to be ruled in or ruled out. For the time being, laboratory confirmation remains essential. More research is needed to develop scientifically validated decision models to inform best practice guidelines and targeted diagnostic algorithms.     

An Integrative Review of American Nurses'' Perceived Cultural Self-Efficacy

PURPOSE: To review use of the Cultural Self-Efficacy Scale (CSES) and to summarize the cumulative findings. METHODS: A combination of literature searches and questionnaires to those who have requested the scale indicated 26 known uses. Fifteen reported sufficient data for statistical analysis. FINDINGS: Of the 26 known uses of the CSES, 8 were published in peer-reviewed journals, 5 in dissertations, 8 in theses, and 3 as data sets only. Two additional theses were not retrievable for the study. On a 5-point Likert-type scale, nurses reported the highest degree of self-efficacy with African American (3.1) and Hispanic (3.1) patients and the lowest with Asian American patients (2.4). Six of the reports include Cronbach's alpha coefficients, ranging from .86 to .98. In the final sample of 15 studies, nurses did not report feeling confident caring for patients from other cultures. CONCLUSIONS: Although the CSES has been used in many settings with over 3,000 nurses, inconsistencies in the data preclude specific conclusions. Further research is needed using consistent reporting practices and sufficient predictor variables to draw further conclusions regarding the scale's psychometric properties.     

Reticulocyte hemoglobin measurement--comparison of two methods in the diagnosis of iron-restricted erythropoiesis.

The aims of this study were to diagnose iron-restricted erythropoiesis (functional iron deficiency) in patients with classic iron deficiency (ID), anemia of chronic disease (ACD) and the combined state of ID/ACD with the use of two hematological methods for the measurement of reticulocyte hemoglobinization. In comparison, the biochemical markers of iron status were determined. We studied 474 anemic patients admitted to hospital with a broad spectrum of diseases. We measured indicators of reticulocyte hemoglobinization. CHr was determined on an Advia 120 hematology analyzer. A Sysmex XE-2100 hematology analyzer was used to determine RET-Y, the forward scatter of fluorescence-labeled reticulocytes, which can also be expressed as the reticulocyte hemoglobin equivalent (RET-H(e)), as well as RBC-Y, the forward scatter of fluorescence-labeled erythrocytes, which can be expressed as the erythrocyte hemoglobin equivalent. Ferritin, soluble transferrin receptor (sTfR) and the sTfR/log ferritin ratio (sTfR-F index) were used as biochemical markers. The comparison of RET-Y with CHr demonstrated an excellent curvilinear relationship between the two parameters. The normal reference range for Ret-Y was 1630-1860 arbitrary units (AU); mathematical transformation to RET-H(e) gave a range of 28.2-35.7 pg. Correlations of biochemical iron markers with RET-H(e) were as weak as with CHr in patients with ACD and acute phase response. In a diagnostic plot to identify iron status, RET-H(e) could replace CHr without any loss of sensitivity or specificity. Patient mismatch analysis between RET-H(e) and CHr in the diagnostic plot demonstrated agreement for 449 of 474 patients (94.4%). Patient specific anemia mismatches were 2.9-6.2%. According to our results, the indicators of reticulocyte hemoglobinization, RET-H(e) and CHr, measure the same phenomenon. RET-H(e) is as valuable as CHr for the diagnosis of iron-restricted erythropoiesis. The combination of RET-H(e) and the sTfR-F index in a diagnostic plot offers an attractive tool for the evaluation of iron status and identification of the progression of ID.     

Inactivation of a Defined Active Site in the Mouse 20S Proteasome Complex Enhances Major Histocompatibility Complex Class I Antigen Presentation of a Murine Cytomegalovirus Protein

Proteasomes generate peptides bound by major histocompatibility complex (MHC) class I molecules. Avoiding proteasome inhibitors, which in most cases do not distinguish between individual active sites within the cell, we used a molecular genetic approach that allowed for the first time the in vivo analysis of defined proteasomal active sites with regard to their significance for antigen processing. Functional elimination of the δ/low molecular weight protein (LMP) 2 sites by substitution with a mutated inactive LMP2 T1A subunit results in reduced cell surface expression of the MHC class I H-2L^d and H-2D^d molecules. Surface levels of H-2L^d and H-2D^d molecules were restored by external loading with peptides. However, as a result of the active site mutation, MHC class I presentation of a 9-mer peptide derived from a protein of murine cytomegalovirus was enhanced about three- to fivefold. Our experiments provide evidence that the δ/LMP2 active site elimination limits the processing and presentation of several peptides, but may be, nonetheless, beneficial for the generation and presentation of others.     

The determination of osteopetrotic phenotypes by selective inactivation of red cell carbonic anhydrase isoenzymes

Red cell carbonic anhydrase isoenzyme activities (HCA-I and HCA-II) were quantitated in blood hemolysates of two female siblings affected with autosomal recessive osteopetrosis in addition to family members who were both obligate and potential heterozygotes as well as normal controls. Selective inactivation of red cell hemolysates with 20 mmol/l bromopyruvic acid (pH 7.5) for 50 min at 25 degrees C lead to a near quantitative removal of HCA-I activity without significant loss of HCA-II activity. Comparison of untreated hemolysate HCA activity with residual activity in bromopyruvate treated samples allowed determination of HCA-II/HCA-I activity ratios. Estimation of activity ratios was also attempted by use of the inhibitor I- which is known to discriminate between the two isoenzymes. Hemolysate HCA activity of the two affected individuals (homozygotes) was completely abolished by the procedure, consistent with an absence of the bromopyruvate resistant HCA-II isoenzyme in the red cells of these individuals. HCA-I activities were found to be elevated significantly above normal. Both parents (obligate heterozygotes) were found to have normal HCA-I activities and HCA-II activities 60-80% of normal. Computed HCA-II/HCA-I activity ratios fell into these ranges: 0 for homozygotes, 0.82-0.87 for obligate heterozygotes and 1.08-1.16 for normal controls. KI values for I- inhibition of hemolysate HCA activity gave 0.25-0.30 mmol/l, 0.9-1.5 mmol/l and 2.0 mmol/l for the three categories. These relations should prove useful in the screening of osteopetrotic phenotypes.     

Caloric restriction for longevity: II—The systematic neglect of behavioural and psychological outcomes in animal research

Research on caloric restriction for longevity (CRL) has generated hundreds of articles on the physiology of food deprivation, yet almost no data on consequences in other domains. The first paper in this series outlined the generally positive physical effects of CRL; the second analyses the meagre and sometimes disturbing record of research on behaviour, cognition and affect. The available evidence suggests that nutrient‐dense CRL in animals—just like nutrient‐poor semi‐starvation in people—is associated with a number of adverse effects. Changes include abnormal food‐related behaviour, heightened aggression and diminished sexual activity. Studies of learning and memory in underfed rodents yield inconsistent findings; no information is available on cognitive effects in primates. To date, the CRL field has ignored other variables that are crucial to the human case and known to be disrupted by chronic hunger, including sociability, curiosity and emotionality. Promotion of CRL for people is irresponsible in the absence of more reassuring data on the full range of expected outcomes. Eating disorder specialists should be contributing to scientific and public discussions of this increasingly prominent paradigm. Copyright © 2004 John Wiley & Sons, Ltd and Eating Disorders Association.     

Early Parkinson's disease: Longitudinal changes in brain activity during sequence learning

Impairment of sequence learning is common in Parkinson's disease (PD), but the time course of this cognitive abnormality is not known. We assessed longitudinal changes in sequence learning performance and associated task-related cerebral blood flow in 13 early stage PD patients who underwent H₂¹⁵O PET at baseline and again 2 years later. Ten healthy volunteer subjects served as controls. A trend toward decline in learning performance (p = 0.08) was evident over the 2 years of follow-up. During this interval, significant declines in learning-related activation were detected in parietal and temporo-occipital association areas and in the right dorsolateral prefrontal cortex. Learning-related activation in these regions was normal at baseline, but declined to subnormal levels (p < 0.01) at 2 years. Significant hippocampal activation (p < 0.005) was present in the subjects with high learning performance over time. The findings are consistent with a decline in learning-related neural activity in cortical areas with prominent Lewy body formation.     

Short-Term Duloxetine Administration Affects Neural Correlates of Mood-Congruent Memory

It is unknown how antidepressants reverse mood-congruent memory bias, a cognitive core factor causing and maintaining depression. Using a double-blind, placebo-controlled, cross-over design, we investigated the effect of a short-term treatment (14 days) with the dual reuptake inhibitor duloxetine on neural correlates of mood-congruent and mood-incongruent memory formation and retrieval in healthy volunteers who underwent a sad mood induction procedure. Duloxetine did not affect acute mood state or memory performance, but interacted with brain processes mediating mood-congruent memory. It decreased activity related to successful memory formation for mood-congruent and -incongruent items in a set of brain regions comprising the putamen and the middle frontal gyrus, as well as the middle and the anterior cingulate cortex. Duloxetine specifically increased amygdala activity related to successful memory retrieval for mood-incongruent items. Here we show that short-term administration of duloxetine affects the neural correlates of emotional memory formation and retrieval in a set of brain regions whose processing is related to affective state and its regulation. While duloxetine suppressed the neural correlates of emotional memory formation in general, it specifically enhanced amygdala processes associated with mood-incongruent memory retrieval. This pattern of results shows how an antidepressant may reduce emotional memory formation and reverse mood-congruent processing biases at retrieval.     

Genetic prion disease with codon 196 PRNP mutation: clinical and pathological findings

Ten percent to 15% of all human transmissible spongiform encephalopathy are characterized by a mutation in prion protein gene (PRNP). They are distinct with respect to clinical signs, disease onset, disease duration, and diagnostic findings. During our surveillance activities in Germany, we identified 7 patients with the rare mutation E196K in PRNP gene, thereof 4 patients belonging to 2 families. The clinical syndromes were characterized by nonspecific and psychiatric symptoms at disease onset and progressed to predominant motor signs. These patients showed a late median disease onset of 71 years and short disease duration of 6.5 months. In absence of family history, they mimicked sporadic Creutzfeldt-Jakob disease (CJD). In clinical tests they were 100% positive for 14-3-3 protein detection in cerebrospinal fluid and less sensitive for magnetic resonance imaging (MRI) and electroencephalogram (EEG) abnormalities. As a secondary magnetic resonance imaging (MRI) abnormality, we have seen conspicuous common involvement of the subcortical white matter in 57%. Four patients underwent autopsy—pathological lesions revealed striking similarity to sporadic Creutzfeldt-Jakob disease but also involvement of the white matter.