bluuebunny/crossref_metadata_2025 huggingface dataset:
A Clinical Approach to “Idiopathic” Normocytic‐Normochromic Anemia
Authors: Elis Avishay , Ravid Mordchai , Manor Yosef , Bental Tamir , Lishner Michael
Published: April 2015

OBJECTIVES: Normocytic‐normochromic anemia is frequently found in patients with chronic disorders. The pathogenesis, epidemiological and clinical characteristics of normocytic normochromic anemia of unknown cause are not well established. We evaluated the role of bone marrow examination and the clinical course of patients with “idiopathic” normocytic‐normochromic anemia.

DESIGN: Patients with normocytic‐normochromic anemia underwent a noninvasive evaluation according to a predetermined protocol. Bone marrow aspiration and biopsy were performed in those patients in whom no explanation for the anemia was found. They were later followed at 3 to 6 month intervals.

RESULTS: Thirty‐one patients (23 females and 8 males) with “idiopathic” normocytic‐normochromic anemia (mean hemoglobin concentration was 10.0 + 0.6 g/dL) were detected. No patient had symptoms related to the anemia. Twenty‐nine bone marrow aspirations and 21 biopsies were performed. Iron deficiency and mild myelofibrosis were found in one patient each. The rest of the bone marrow examinations were normal. During 15.5 ± 10.3 months of follow‐up, the hemoglobin level rose marginally to 10.9 + 1.0 g/dL (P < .0002). No changes in clinical or laboratory variables that could be ascribed to anemia were detected.

CONCLUSION: Normocytic‐normochromic anemia of unknown cause is encountered infrequently in clinical practice and is found mainly in older patients. The evaluation should be noninvasive to exclude correctable causes of the anemia. Bone marrow examination is only rarely contributive in this setting. The prognosis of these patients is excellent.
HEALTH SERVICES RESEARCH: The Effectiveness and Efficiency of Outpatient Geriatric Evaluation and Management
Authors: Engelhardt Joseph B. , Toseland Ronald W. , O'Donnell John C. , Richie Jill T. , Jue Donald , Banks Steve
Published: April 2015

OBJECTIVES: To compare the effectiveness of geriatric evaluation and management (GEM) with usual primary care (UPC).

DESIGN: A 2 × 3 randomized controlled group design.

SETTING: A 450‐bed Department of Veterans Affairs Medical Center (VAMC) that provides general medical and surgical care to eligible veterans.

PARTICIPANTS: One‐hundred sixty male subjects (mean age = 72 years), who were above average users of VAMC outpatient clinics and who had at least two Activity of Daily Living (ADL) or Instrumental Activity of Daily Living (IADL) impairments, were assigned to GEM (n = 80) or UPC (n = 80).

MEASUREMENTS: Data were collected about patients' (1) health and functional status, (2) psychosocial well‐being, (3) quality of health and social care, (4) health care utilization, and (5) health care costs. Data were obtained before randomization, and again at 8 and 16 months.

RESULTS: The results indicated that GEM was more effective than UPC in improving some aspects of the quality of health and social care and in increasing patient satisfaction with care. GEM also reduced emergency room use, and showed a trend toward decreasing acute admissions. It was not effective, however, in improving patients' psychosocial well‐being. Except for a short‐term survival advantage, it was also not effective in preventing deterioration in their health and functional status. Further, GEM did not reduce overall utilization of outpatient or inpatient services, and it significantly increased total outpatient health care costs.

CONCLUSIONS: Outpatient GEM improves patient satisfaction and some aspects of the quality of care patients' receive but does not reduce the cost of outpatient or inpatient care. Longer‐term follow‐up studies are needed to determine whether reductions in emergency room use and inpatient admissions persist over time and result in reductions in the overall cost of care.
Hospital‐Acquired Pressure Ulcers and Risk of Death
Authors: Thomas David R. , Goode Patricia S. , Tarquine Paige Huber , Allman Richard M.
Published: April 2015

OBJECTIVE: To evaluate the impact of in‐hospital pressure ulcer development on mortality among older, high‐risk, hospitalized patients up to 1 year post‐hospital discharge, after adjusting for baseline patient characteristics, disease severity, hospital complications, and discharge activity level.

DESIGN: A prospective, inception, cohort study.

SETTING: An urban, tertiary, acute care, university teaching hospital.

PATIENTS: A total of 286 patients aged 55 or older, expected to be confined to bed or chair for at least 5 days, who were admitted to the hospital without a Stage 2 or greater pressure ulcer.

MEASUREMENTS: The primary outcome measurement was time to death from admission to 1‐year post‐hospital discharge. Baseline information included demographic, medical, functional, and nutritional variables known to be associated with increased mortality. Measures of global disease severity and co‐morbidity included the admitting physician's estimate of illness severity and life expectancy, the acute physiology score of APACHE II, the Co‐morbidity Damage Index, and the Medicus Nursing Classification Score. Baseline infections, incident infections, and noninfectious hospital complications were determined. Functional activity level was determined at hospital discharge. Post‐discharge vital status was determined by telephone interviews at 3, 6, 9, and 12 months after discharge and confirmed by death certificate review.

MAIN RESULTS: Development of an in‐hospital pressure ulcer was associated with greater risk of death at 1 year (59.5% vs 38.2%, P = .02). However, pressure ulcer development did not remain independently associated with decreased survival after adjusting for other predictors of mortality. Predictors of mortality at hospital admission by multivariate Cox regression analysis included weight loss in the 6 months before admission (RR 2.4, CI 1.6, 3.6), physician estimate of life expectancy (RR 2.1, CI 1.7, 2.6), and the Co‐morbidity Damage Index (RR 1.1, CI 1.0, 1.2). Multivariate predictors of 1‐year mortality at discharge included physician estimate of life expectancy (RR 2.2, CI 1.8, 2.6), weight loss in the 6 months before admission (RR 2.2, CI 1.5, 3.2), remaining confined to bed or chair (RR 1.9, CI 1.2, 3.1), and the total number of hospital complications (RR 1.3, CI 1.2, 1.5).

CONCLUSIONS: Pressure ulcers that develop during acute hospitalization are not associated with reduced 1‐year survival among high risk older persons after adjusting for nutritional and functional status, global measures of disease severity and co‐morbidity, and noninfectious hospital complications.
A Population‐Based Study on the Incidence of Dementia Disorders Between 85 and 88 Years of Age
Authors: Aevarsson Olafur , Skoog Ingmar
Published: April 2015

OBJECTIVE: To investigate the incidence of Alzheimer's disease, vascular dementia and other dementias in a population between 85 and 88 years of age.

DESIGN: Prospective cohort study. Longitudinal population study of the very old.

SETTING: Systematic sample of a birth cohort living in the community or in institutions in the city of Gothenburg, Sweden.

PARTICIPANTS: A representative population sample of nondemented 85‐year‐old residents (n = 347).

MEASUREMENTS: The study included neuropsychiatric, neuropsychological, and physical examinations, key informant interviews, comprehensive laboratory tests, electrocardiography, chest radiography and computed tomography (CT‐scan) of the head. Information on subjects lost during the follow‐up period as a result of death or refusal was traced in medical records. Dementia was defined according to the criteria proposed in the Diagnostic and Statistical Manual of Mental Disorders (3rd Edition, revised), Alzheimer's disease according to the criteria of the National Institute of Neurological and Communicative Disorders and Stroke and the Alzheimer's Disease and Related Disorders Association, and vascular dementia according to criteria proposed by Erkinjuntti.

RESULTS: Sufficient information was obtained about 92% of the subjects at risk. Sixty‐three subjects (18.2%) became demented between ages 85 and 88, giving an incidence of 90.1/1000/year (61.3/1000/year for men and 102.7/1000/year for women; P = .085). The incidence of Alzheimer's disease was 36.3/1000/year, vascular dementia 39.0/1000/year (P = 1.000), and that of other dementias 9.1/1000/year.

CONCLUSION: This study shows that almost one‐tenth of nondemented persons between the ages of 85 and 88 become demented each year, emphasizing the magnitude of the dementia problem in the very old, the fastest growing segment of western populations.
Factors Affecting Sample Selection in a Randomized Trial of Balance Enhancement: The FICSIT Study
Authors: Pacala James T. , Judge James Oat , Boult Chad
Published: April 2015

OBJECTIVE: To determine demographic, functional, and health‐related factors that may have influenced the selection of older adults for a randomized trial of balance enhancement.

DESIGN: Comparison of participants with nonparticipants at various stages of the recruiting process.

SETTING: Northeastern suburban community.

PARTICIPANTS: Registered voters aged 75 and older (n = 7191).

MEASUREMENTS: Demographic, health‐related, functional, balance, gait, and falling characteristics.

RESULTS: The overall participation rate in the randomized trial was 1.5%. Compared with nonparticipants, participants were significantly more likely to be male, married, living with others, living in a house, highly educated, healthy, and physically active.

CONCLUSION: Recruiting older subjects by mail to studies of rigorous interventions can produce significant selection biases that may limit the population to which results can be generalized. J Am Geriatr Soc 44:377–382, 1996.
Intraindividual Reproducibility of Postprandial and Orthostatic Blood Pressure Changes in Older Nursing‐Home Patients: Relationship with Chronic Use of Cardiovascular Medications
Authors: Jansen René W.M.M. , Kelley‐Gagnon Margaret M. , Lipsitz Lewis A.
Published: April 2015

OBJECTIVES: Although postprandial and orthostatic hypotension are commonly observed in nursing home residents, their reproducibility, relationship to each other, and association with chronic use of cardiovascular medications are poorly understood.

DESIGN: We examined blood pressure (BP) and heart rate (HR) before and after postural change, and before and after a 419‐kcal meal in 22 nursing home residents (mean age 89 ± 5 (SD) years), each on two occasions, to determine reproducibility of changes. These studies were repeated in 17 residents, with and without previous administration of cardiovascular medications, in random order.

SETTING: Hebrew Rehabilitation Center for the Aged, an academic long‐term care facility.

RESULTS: Systolic BP declined an average (± SE) of 16 ± 4 mm Hg and 12 ± 4 mm Hg during the first and second meal studies, respectively. Mean intra‐class correlation of postprandial systolic BP values during the two studies was 0.88 (95% CI 0.85–0.97). Systolic BP increased significantly during the first posture test to a maximum of 8 ± 6 mm Hg at 6 minutes. There was no significant difference over time in postural systolic BP between the two tests. Repeated postural studies showed a mean intra‐class correlation of 0.72 (95% CI 0.62–0.92) for changes in systolic BP. Cardiovascular medications had no additional effect on mean postprandial or orthostatic BP and HR changes. During the first studies, 10 subjects had postprandial hypotension, and three subjects had orthostatic hypotension, but only two of 22 subjects had both.

CONCLUSIONS: Patterns of systolic BP response to meals or postural change are reproducible. BP responses to meals and postural change seem to be unaffected by potentially hypotensive medications in chronic users. Postprandial hypotension is distinct from orthostatic hypotension, occurring more commonly than orthostatic hypotension and infrequently together in the same patients. J Am Geriatr Soc 44:383–389, 1996.
Breast Cancer in Women 70 Years of Age or Older
Authors: Masetti Riccardo , Antinori Armando , Terribile Daniela , Marra Alessandro , Granone Pierluigi , Magistrelli Paolo , Picciocchi Aurelio
Published: April 2015

OBJECTIVES: To investigate the impact of age as a prognostic factor in older patients with breast cancer and to discuss the role of surgery in this category of patients.

DESIGN: A retrospective study.

SETTING: A tertiary care university teaching hospital.

PARTICIPANTS: One hundred ninety patients aged 70 years or older (mean age: 75 years) were treated for breast cancer from 1967 through 1991. These patients were compared with 190 younger patients (mean age: 52 years) and matched on the basis of T and N categories (TNM staging system) and surgical procedures.

MEASUREMENTS: Disease‐free survival, breast cancer‐specific survival.

RESULTS: The 10‐year actuarial breast cancer‐specific survival was 66% for older patients and 56% for younger patients (P= .224). The 10‐year actuarial disease‐free survival was 54% for older patients and 45% for younger patients (P= .136). Univariate and multivariate survival analysis revealed that tumor size and nodal stage were significant prognostic factors for both older and younger patients.

CONCLUSION: Treatment with curative intent, similar to that adopted in younger patients, is appropriate for women over the age of 70 with breast cancer.J Am Geriatr Soc 44:390–393, 1996.
The Effects of Antihypertensive Treatment on Cognitive Function: Results from the HOPE Study
Authors: Starr John M. , Whalley Lawrence J. , Deary Ian J.
Published: April 2015

OBJECTIVES: Hypertension is associated with impaired cognition, but it is unclear whether this impairment is reversible. We sought to evaluate the effect of blood pressure reduction on cognition.

DESIGN: A randomized, double‐blind trial.

SETTING: A single center, with assessments in subjects' domiciles.

PARTICIPANTS: Community‐screened subjects more than 69 years of age who had median diastolic pressures > 99 mm Hg and systolic pressures > 159 mm Hg or diastolic > 85 mm Hg and systolic >179 mm Hg with Mini‐Mental State Examination scores of 20 to 28. Subjects had not previously received antihypertensive treatment.

INTERVENTION: Captopril 12.5 mg twice daily or bendrofluazide 2.5 mg daily for 24 weeks, preceded by a 2‐week placebo phase.

MEASUREMENTS: Cognition was evaluated by a psychometric test battery comprising Immediate and Delayed Logical Memory, Paired Associates recall, Raven's Progressive Matrices, Halstead Reitan Trail Making A, and the Anomalous Sentences Repetition Test.

RESULTS: Eighty‐one subjects (28 male, 53 female) were treated (41 captopril, 40 bendrofluazide). At entry, mean age was 76.1 years (range 70–84), mean blood pressure was 191 (160–230) mm Hg systolic, 101 (88–110) mm Hg diastolic, and mean MMSE score 26.1. A total of 69 subjects completed the trial. The 25th, 50th, and 75th percentiles of the difference between pretreatment and Week 24 blood pressures were 15 mm Hg, 35 mm Hg, and 50 mm Hg (systolic) and 5 mmHg, 10 mm Hg, and 19 mm Hg (diastolic). There were no significant differences in any psychometric test between captopril and bendrofluazide. The 19 subjects in the quartile that lowered their diastolic blood pressure most (≥ 19 mm Hg) had improved scores on Anomalous Sentences (P = .012) and Paired Associates (P = .044) compared to the 19 subjects in the least blood pressure responsive quartile (fall ≤ 5 mm Hg)s

CONCLUSION: The treatment of hypertension is not hazardous to cognitive function in older people with pre‐existing cognitive impairment. Long‐term adequate blood pressure control may reverse cognitive impairment associated with pre‐existing hypertension. J Am Geriatr Soc 44:411–415, 1996.
Pyuria Among Chronically Incontinent but Otherwise Asymptomatic Nursing Home Residents
Authors: Ouslander Joseph G. , Schapira Moises , Schnelle John F. , Fingold Susan
Published: April 2015

OBJECTIVE: To determine the prevalence of pyuria and its relationship to bacteriuria in a representative sample of chronically incontinent nursing home residents.

DESIGN: Prospective, descriptive case series.

SETTING: Six nursing homes.

PARTICIPANTS: Two hundred fourteen chronically incontinent, but otherwise asymptomatic, nursing home residents who were enrolled in a clinical intervention trial for urinary incontinence.

MEASURES: Two hundred fourteen urine specimens were collected by a validated clean catch technique. Each specimen underwent dipstick testing for leukocyte esterase, microscopic urinalysis to determine the number of white blood cells per high power field of centrifuged urine, and quantitative urine culture using standard laboratory techniques.

RESULTS: The overall prevalence of pyuria was 45%, as defined by > 10 white blood cells per high field of spun urine, and the overall prevalence of bacteriuria was 43%, as defined by the growth of >100,000 colony forming units of a urinary pathogen. Fifty‐nine percent of the specimens with bacteriuria and 34% of the specimens without bacteriuria had pyuria. Of specimens with pyuria, 56% had bacteriuria, and of specimens without pyuria, 31% had bacteriuria. When any color change on the leukocyte esterase pad was considered positive, this finding had a sensitivity of 83% and a specificity of 52% for pyuria on microscopic urinalysis.

CONCLUSIONS: Pyuria is common among chronically incontinent nursing home residents, both in the presence and absence of bacteriuria. Clinicians must therefore be cautious in interpreting the presence of pyuria to indicate symptomatic infection in this population. Using pyuria to determine the need for antimicrobial treatment could result in unnecessary expense and morbidity as well as contribute to the development of resistant organisms in nursing homes. Research is needed to define pyuria better, to determine its prevalence and relationship to bacteriuria among nursing home residents with symptoms of acute urinary tract infection, and to elucidate the etiology and significance of sterile pyuria in this population. J Am Geriatr Soc 44:420–423, 1996.
Effects of Prompted Voiding on Fecal Continence Among Nursing Home Residents
Authors: Ouslander Joseph G. , Simmons Sandra , Schnelle John , Uman Gwen , Fingold Susan
Published: April 2015

OBJECTIVE: To determine the effects of prompted voiding on fecal continence in nursing home residents.

DESIGN: Prospective, uncontrolled trial of prompted voiding for urinary incontinence.

PARTICIPANTS: One hundred sixty‐five nursing home residents who completed a 9 to 10‐week trial.

MEASUREMENTS: Trained research aides performed physical checks for urinary and fecal incontinence hourly from 8 AM to 6 PM for 3 days (total of 33 checks) at baseline, for the last 3 days of a 1‐week trial of prompted voiding, and after 9 to 10 weeks of prompted voiding.

RESULTS: After 9 to 10 weeks of prompted voiding, there was no significant change in the frequency of incontinent bowel movements per resident (1.1 [95% CI .83, 1.4] to .87 [95% CI.67, 1.1]; P = 0.140). There was a significant increase in the number of continent bowel movements per resident (.17 [95% CI.10, .24] to .62 [95% CI.45, .80]; P = .000). This increase occurred in residents whose urinary incontinence responded well to prompted voiding as well as those whose urinary incontinence did not respond. The percentage of bowel movements that were continent also increased significantly from 18% (95% CI 8,29) at baseline to 45% (95% CI 32,57) after 9 to 10 weeks of intervention (P = .000). In addition to these findings, we noted a marked increase in the total frequency of bowel movements after the first week of prompted voiding. This may have resulted from the relief of fecal impactions caused by the increased toileting, mobility, and fluid intake that occurred with prompted voiding.

CONCLUSION: Prompted voiding did not change the frequency of incontinent bowel movements significantly in this sample of nursing home residents. However, the number of continent bowel movements and the percentage of bowel movements that were continent did increase. Our data must be interpreted cautiously because our study was designed primarily as an intervention for urinary, not fecal, incontinence and the design was neither blinded nor controlled. Trials of systematic toileting schedules specifically directed at fecal incontinence, with attention to fecal impaction, diet, fluid intake and laxative use, should be conducted. J Am Geriatr Soc 44:424–428, 1996.
Shoe Characteristics and Balance in Older Women
Authors: Lord Stephen R. , MBBS Guy M Bashford
Published: April 2015

OBJECTIVE: To determine whether shoe characteristics affect balance in older women.

DESIGN: Randomized order, cross‐over, controlled comparison.

SETTING: A retirement village.

PARTICIPANTS: Thirty women aged 60 to 89 years (mean 78.7 SD = 8.5). Twenty‐five subjects were hostel residents, and five were living independently in the community.

OUTCOME MEASURES: Postural sway, maximal balance range, and co‐ordinated stability.

MAIN RESULTS: The subjects underwent assessments of static balance (body sway) and dynamic balance (maximal balance range and co‐ordinated stability) under four conditions: (1) barefoot, (2) in standard low‐heeled shoes (walking shoes), (3) in standard high‐heeled shoes, and (4) in their own shoes. Manova analysis revealed a significant overall shoe condition effect — subjects performed best in bare feet or low‐heeled shoes and worst in high‐heeled shoes. There were no significant differences between subjects with and without foot abnormalities in any of the balance measures or test conditions.

CONCLUSION: These findings suggest that bare feet and walking shoes maximize balance, whereas high‐heeled shoes constitute a needless balance hazard for older women. J Am Geriatr Soc 44:429–433, 1996.
Human umbilical cord mesenchymal stem cell transplantation restores damaged ovaries
Authors: Zhu Shao‐Fang , Hu Hong‐Bo , Xu Hong‐Yan , Fu Xia‐Fei , Peng Dong‐Xian , Su Wei‐Yan , He Yuan‐Li
Published: April 2015

Ovarian injury because of chemotherapy can decrease the levels of sexual hormones and potentia generandi of patients, thereby greatly reducing quality of life. The goal of this study was to investigate which transplantation method for human umbilical cord mesenchymal stem cells (HUMSCs) can recover ovarian function that has been damaged by chemotherapy. A rat model of ovarian injury was established using an intraperitoneal injection of cyclophosphamide. Membrane‐labelled HUMSCs were subsequently injected directly into ovary tissue or tail vein. The distribution of fluorescently labelled HUMSCs, estrous cycle, sexual hormone levels, and potentia generandi of treated and control rats were then examined. HUMSCs injected into the ovary only distributed to the ovary and uterus, while HUMSCs injected via tail vein were detected in the ovary, uterus, kidney, liver and lung. The estrous cycle, levels of sex hormones and potentia generandi of the treated rats were also recovered to a certain degree. Moreover, in some transplanted rats, fertility was restored and their offspring developed normally. While ovary injection could recover ovarian function faster, both methods produced similar results in the later stages of observation. Therefore, our results suggest that transplantation of HUMSCs by tail vein injection represents a minimally invasive and effective treatment method for ovarian injury.
5‐Hydroxytryptamine Medications for the Treatment of Obesity
Authors: Burke L. K. , Heisler L. K.
Published: April 2015

The central 5‐hydroxytryptamine (5‐HT; serotonin) system represents a fundamental component of the brain's control of energy homeostasis. Medications targeting the 5‐HT pathway have been at the forefront of obesity treatment for the past 15 years. Pharmacological agents targeting 5‐HT receptors (5‐HTR), in combination with genetic models of 5‐HTR manipulation, have uncovered a role for specific 5‐HTRs in energy balance and reveal the 5‐HT2CR as the principal 5‐HTR mediating this homeostatic process. Capitalising on this neurophysiological machinery, 5‐HT2CR agonists improve obesity and glycaemic control in patient populations. The underlying therapeutic mechanism has been probed using model systems and appears to be achieved primarily through 5‐HT2CR modulation of the brain melanocortin circuit via activation of pro‐opiomelanocortin neurones signalling at melanocortin4 receptors. Thus, 5‐HT2CR agonists offer a means to improve obesity and type 2 diabetes, which are conditions that now represent global challenges to human health.
A novel application of radiomimetic compounds as antibiotic drugs
Authors: Andros Christina C , Dubay Ryan A , Mitchell Kayleigh D , Chen Aaron , Holmes Dawn E , Kennedy Daniel R
Published: April 2015

Objective

This study aims to examine the potential of radiomimetic compounds as antimicrobial therapeutics, as the recent advances in radiomimetic targeting as well as rapid increase of multidrug resistant bacteria make these compounds attractive for future development.

Methods

Representative radiomimetics from each of the three major categories was examined; C-1027 and neocarzinostatin from the protein-chromophore enediyne family; Calicheamicin from the non-protein chromophore enediyne family and Bleomycin and Tallysomycin S10b from the glycopeptide family. The activity of these compounds was examined against 12 distinct bacteria species. Inhibition was determined using disc diffusion assays and a subsequent examination of minimum inhibitory concentration of a representative organism. The onset of action of the compounds was also determined by incubating the organisms with drug in liquid media, before plating, and then determining if growth occurred.

Results

We found that the radiomimetic glycopeptides were more active against Gram-negative species, while the enediynes were more effective against Gram-positive species. The radiomimetics also maintained their rapid onset of action, working as quickly as 5 min.

Conclusions

Radiomimetic compounds have activity against a wide variety of microorganisms and would support the development of radiomimetic–antibody conjugates as potential antibiotics as an option against severe bacterial infections.
International Employment Statistics for People With Intellectual Disability—The Case for Common Metrics
Authors: Lysaght Rosemary , Šiška Jan , Koenig Oliver
Published: April 2015

The World Report on Disability identifies employment as an important element of social participation. The Report also points to the need for research that crosses national boundaries to identify and address central areas of concern. However, such efforts are hampered with respect to intellectual disability (ID) by inconsistencies in the population definitions used, the definition of employment or employability, and metrics of employment participation. The authors explore the varied ways in which employment participation rates for people with ID are determined and reported in jurisdictions around the world, and note that with respect to employment metrics, there remains substantial variation in the methods used in data collection and reporting across agencies and countries. They also note that close inspection of methodologies is required in order to interpret data from any official statistical agency (as even when methods and definitions are explicit, the variations in approaches make comparisons difficult). Recommendations for harmonizing disparate definitions and metrics include a systematic analysis of the terminology and methods used in national surveys that would assist in identifying which data are comparable, agreement on a protocol and process for examining employment outcomes in the ID population, and the creation of an international panel on employment and ID charged to identify common terminology and population parameters to be specified in sample selection and description in localized research and studies.
Specific gamma‐aminobutyrate chemotaxis in pseudomonads with different lifestyle
Authors: Reyes‐Darias Jose Antonio , García Vanina , Rico‐Jiménez Miriam , Corral‐Lugo Andrés , Lesouhaitier Olivier , Juárez‐Hernández Dalia , Yang Yiling , Bi Shuangyu , Feuilloley Marc , Muñoz‐Rojas Jesús , Sourjik Victor , Krell Tino
Published: April 2015

The PctC chemoreceptor of Pseudomonas aeruginosa mediates chemotaxis with high specificity to gamma‐aminobutyric acid (GABA). This compound is present everywhere in nature and has multiple functions, including being a human neurotransmitter or plant signaling compound. Because P. aeruginosa is ubiquitously distributed in nature and able to infect and colonize different hosts, the physiological relevance of GABA taxis is unclear, but it has been suggested that bacterial attraction to neurotransmitters may enhance virulence. We report the identification of McpG as a specific GABA chemoreceptor in non‐pathogenic Pseudomonas putida KT2440. As with PctC, GABA was found to bind McpG tightly. The analysis of chimeras comprising the PctC and McpG ligand‐binding domains fused to the Tar signaling domain showed very high GABA sensitivities. We also show that PctC inactivation does not alter virulence in Caenorhabditis elegans. Significant amounts of GABA were detected in tomato root exudates, and deletion of mcpG reduced root colonization that requires chemotaxis through agar. The C. elegans data and the detection of a GABA receptor in non‐pathogenic species indicate that GABA taxis may not be related to virulence in animal systems but may be of importance in the context of colonization and infection of plant roots by soil‐dwelling pseudomonads.
Aggregatibacter actinomycetemcomitans QseBC is activated by catecholamines and iron and regulates genes encoding proteins associated with anaerobic respiration and metabolism
Authors: Weigel W.A. , Demuth D.R. , Torres‐Escobar A. , Juárez‐Rodríguez M.D.
Published: April 2015

Aggregatibacter actinomycetemcomitans QseBC regulates its own expression and is essential for biofilm growth and virulence. However, the signal that activates the QseC sensor has not been identified and the qseBC regulon has not been defined. In this study, we show that QseC is activated by catecholamine hormones and iron but not by either component alone. Activation of QseC requires an EYRDD motif in the periplasmic domain of the sensor and site‐specific mutations in EYRDD or the deletion of the periplasmic domain inhibits catecholamine/iron‐dependent induction of the ygiW‐qseBC operon. Catecholamine/iron‐dependent induction of transcription also requires interaction of the QseB response regulator with its binding site in the ygiW‐qseBC promoter. Whole genome microarrays were used to compare gene expression profiles of A. actinomycetemcomitans grown in a chemically defined medium with and without catecholamine and iron supplementation. Approximately 11.5% of the A. actinomycetemcomitans genome was differentially expressed by at least two‐fold upon exposure to catecholamines and iron. The expression of ferritin was strongly induced, suggesting that intracellular iron storage capacity is increased upon QseBC activation. Consistent with this, genes encoding iron binding and transport proteins were down‐regulated by QseBC. Strikingly, 57% of the QseBC up‐regulated genes (56/99) encode proteins associated with anaerobic metabolism and respiration. Most of these up‐regulated genes were recently reported to be induced during in vivo growth of A. actinomycetemcomitans. These results suggest that detection of catecholamines and iron by QseBC may alter the cellular metabolism of A. actinomycetemcomitans for increased fitness and growth in an anaerobic host environment.
An Excel tool for deriving key photosynthetic parameters from combined gas exchange and chlorophyll fluorescence: theory and practice
Authors: Bellasio Chandra , Beerling David J , Griffiths Howard
Published: April 2015

Combined photosynthetic gas exchange and modulated fluorometres are widely used to evaluate physiological characteristics associated with phenotypic and genotypic variation, whether in response to genetic manipulation or resource limitation in natural vegetation or crops. After describing relatively simple experimental procedures, we present the theoretical background to the derivation of photosynthetic parameters, and provide a freely available Excel‐based fitting tool (EFT) that will be of use to specialists and non‐specialists alike. We use data acquired in concurrent variable fluorescence–gas exchange experiments, where A/Ci and light–response curves have been measured under ambient and low oxygen. From these data, the EFT derives light respiration, initial PSII (photosystem II) photochemical yield, initial quantum yield for CO2 fixation, fraction of incident light harvested by PSII, initial quantum yield for electron transport, electron transport rate, rate of photorespiration, stomatal limitation, Rubisco (ribulose 1·5‐bisphosphate carboxylase/oxygenase) rate of carboxylation and oxygenation, Rubisco specificity factor, mesophyll conductance to CO2 diffusion, light and CO2 compensation point, Rubisco apparent Michaelis–Menten constant, and Rubisco CO2‐saturated carboxylation rate. As an example, a complete analysis of gas exchange data on tobacco plants is provided. We also discuss potential measurement problems and pitfalls, and suggest how such empirical data could subsequently be used to parameterize predictive photosynthetic models.
Enhanced bioturbation on the down‐drift flank of a Turonian asymmetrical delta: Implications for seaway circulation, river nutrients and facies models
Authors: Korus Jesse T. , Fielding Christopher R.
Published: April 2015

Extant models predict delta front environments down‐drift of river mouths as unfavourable for organisms because of the physico‐chemical stresses caused by sediment and fresh water influx. This study, however, finds evidence for near‐optimal living conditions down‐drift of contemporaneous mouth bars and distributary channels, as well as at the tops of abandoned lobes, in part of the asymmetrical ‘Notom Delta’ complex of the Ferron Sandstone (Turonian, south‐eastern Utah, USA). Presented herein is a sedimentological and ichnological model using thirty‐two detailed measured sections along a 16 km transect through two continuously exposed, ca 10 m thick allomembers containing delta front, mouth bar and distributary channel facies. Azimuths from sedimentary structures show south‐eastward deflection of near‐shore palaeocurrents relative to the inferred north–south shoreline, as well as minor reversal of flow. Two end‐member trace fossil suites are recognized in delta front sandstones: (i) a stressed suite of low abundance, low diversity, diminutive traces reflecting mobile deposit feeding, resting and locomotion behaviours; and (ii) a comparatively unstressed, high abundance, moderate diversity suite with a regular, heterogeneous distribution of deep, vertical or U‐shaped suspension‐feeding burrows which, in places, thoroughly homogenize the sandstones. The down‐drift side of the delta was colonized by suspension feeders during seasonal reversal of the seaway gyre when mud plumes were swept northward or when river‐derived nutrients were sufficiently concentrated relative to fresh water and sediment input. During normal seaway circulation, very high sedimentation rates and mud‐laden, wave‐dampened waters down‐drift of the river mouths heightened the preservation potential of the pervasively bioturbated facies. Up‐drift of the river mouths, these bioturbated facies were either not preserved or not developed until the lobe was abandoned. This alternative model for delta planform asymmetry contributes to the refinement of facies models for deltaic systems and provides a framework for predicting the distribution of bioturbation‐enhanced porosity and permeability in lobe‐deflected deltas.
Suicide in the City: Do Characteristics of Place Really Influence Risk?*
Authors: Denney Justin T. , Wadsworth Tim , Rogers Richard G. , Pampel Fred C.
Published: April 2015

Objective

This article investigates the role of social context on individual suicide mortality with attention paid to the possibility that contextual effects are simply the sum of individual characteristics associated with suicide.

Methods

We use restricted data from the 1986–2006 National Health Interview Survey‐Linked Mortality Files, which include nearly 1 million records and 1,300 suicides, to examine the role of familial and socioeconomic context on adult suicide.

Results

Results show that adults living in cities with more socioeconomic disadvantage and fewer families living together have higher odds of suicidal death than adults living in less disadvantaged cities and cities with more families living together, respectively, after controlling for individual‐level socioeconomic status, marital status, and family size.

Conclusion

The findings support classic sociological arguments that the risk of suicide is indeed influenced by the social milieu and cannot simply be explained by the aggregation of individual characteristics.
Environmental perception and epigenetic memory: mechanistic insight through FLC
Authors: Berry Scott , Dean Caroline
Published: April 2015

Chromatin plays a central role in orchestrating gene regulation at the transcriptional level. However, our understanding of how chromatin states are altered in response to environmental and developmental cues, and then maintained epigenetically over many cell divisions, remains poor. The floral repressor gene FLOWERING LOCUS C (FLC) in Arabidopsis thaliana is a useful system to address these questions. FLC is transcriptionally repressed during exposure to cold temperatures, allowing studies of how environmental conditions alter expression states at the chromatin level. FLC repression is also epigenetically maintained during subsequent development in warm conditions, so that exposure to cold may be remembered. This memory depends on molecular complexes that are highly conserved among eukaryotes, making FLC not only interesting as a paradigm for understanding biological decision‐making in plants, but also an important system for elucidating chromatin‐based gene regulation more generally. In this review, we summarize our understanding of how cold temperature induces a switch in the FLC chromatin state, and how this state is epigenetically remembered. We also discuss how the epigenetic state of FLC is reprogrammed in the seed to ensure a requirement for cold exposure in the next generation.
Development of Disease‐specific, Context‐specific Surveillance Models: Avian Influenza (H5N1)‐Related Risks and Behaviours in African Countries
Authors: Fasina F. O. , Njage P. M. K. , Ali A. M. M. , Yilma J. M. , Bwala D. G. , Rivas A. L. , Stegeman A. J.
Published: April 2015

Avian influenza virus (H5N1) is a rapidly disseminating infection that affects poultry and, potentially, humans. Because the avian virus has already adapted to several mammalian species, decreasing the rate of avian–mammalian contacts is critical to diminish the chances of a total adaptation of H5N1 to humans. To prevent the pandemic such adaptation could facilitate, a biology‐specific disease surveillance model is needed, which should also consider geographical and socio‐cultural factors. Here, we conceptualized a surveillance model meant to capture H5N1‐related biological and cultural aspects, which included food processing, trade and cooking‐related practices, as well as incentives (or disincentives) for desirable behaviours. This proof of concept was tested with data collected from 378 Egyptian and Nigerian sites (local [backyard] producers/live bird markets/village abattoirs/commercial abattoirs and veterinary agencies). Findings revealed numerous opportunities for pathogens to disseminate, as well as lack of incentives to adopt preventive measures, and factors that promoted epidemic dissemination. Supporting such observations, the estimated risk for H5N1‐related human mortality was higher than previously reported. The need for multidimensional disease surveillance models, which may detect risks at higher levels than models that only measure one factor or outcome, was supported. To develop efficient surveillance systems, interactions should be captured, which include but exceed biological factors. This low‐cost and easily implementable model, if conducted over time, may identify focal instances where tailored policies may diminish both endemicity and the total adaptation of H5N1 to the human species.
Angiotensin‐dependent autonomic dysregulation precedes dilated cardiomyopathy in a mouse model of muscular dystrophy
Authors: Sabharwal Rasna , Weiss Robert M. , Zimmerman Kathy , Domenig Oliver , Cicha Michael Z. , Chapleau Mark W.
Published: April 2015

New Findings

What is the central question of this study?

Is autonomic dysregulation in a mouse model of muscular dystrophy dependent on left ventricular systolic dysfunction and/or activation of the renin–angiotensin system (RAS) and does it predict development of dilated cardiomyopathy (DCM)?

What is the main finding and its importance?

The results demonstrate that autonomic dysregulation precedes and predicts left ventricular dysfunction and DCM in sarcoglycan‐δ‐deficient (Sgcd−/−) mice. The autonomic dysregulation is prevented by treatment of young Sgcd−/− mice with the angiotensin II type 1 receptor blocker losartan. Measurements of RAS activation and autonomic dysregulation may predict risk of DCM, and therapies targeting the RAS and autonomic dysregulation at a young age may slow disease progression in patients.

Sarcoglycan mutations cause muscular dystrophy. Patients with muscular dystrophy develop autonomic dysregulation and dilated cardiomyopathy (DCM), but the temporal relationship and mechanism of autonomic dysregulation are not well understood. We hypothesized that activation of the renin–angiotensin system (RAS) causes autonomic dysregulation prior to development of DCM in sarcoglycan‐δ‐deficient (Sgcd−/−) mice and that the severity of autonomic dysfunction at a young age predicts the severity of DCM at older ages. At 10–12 weeks of age, when left ventricular function assessed by echocardiography remained normal, Sgcd−/− mice exhibited decreases in arterial pressure, locomotor activity, baroreflex sensitivity and cardiovagal tone and increased sympathetic tone compared with age‐matched C57BL/6 control mice (P < 0.05). Systemic and skeletal muscle RAS were activated, and angiotensin II type 1 receptor (AT1R) expression, superoxide and fibrosis were increased in dystrophic skeletal muscle (P < 0.05). Treatment with the AT1R blocker losartan for 7–9 weeks beginning at 3 weeks of age prevented or strongly attenuated the abnormalities in Sgcd−/− mice (P < 0.05). Repeated assessment of phenotypes between 10 and 75 weeks of age demonstrated worsening of autonomic function, progressive cardiac dysfunction and DCM and increased mortality in Sgcd−/− mice. High sympathetic tone predicted subsequent left ventricular dysfunction. We conclude that activation of the RAS causes severe autonomic dysregulation in young Sgcd−/− mice, which portends a worse long‐term prognosis. Therapeutic targeting of the RAS at a young age may improve autonomic function and slow disease progression in muscular dystrophy.
On Crack Control Strategy in Near-Field Microwave Drilling of Soda Lime Glass Using Precursors
Authors: Lautre Nitin Kumar , Sharma Apurbba Kumar , Das Shantanu , Kumar Pradeep
Published: April 2015

Processing of glass is indeed challenging owing to its chemical passivity; it is prone to cracking while processing through mechanical and thermal modes without appropriate strategies. Near-field microwave drilling is a thermal-ablation based material removal technique of generating high heat flux in the targeted area. Glasses tend to fail quite frequently during this processing owing to thermal stresses (shock). It was therefore important to develop suitable strategies to minimize cracking during this potentially pragmatic process for microdrilling. Accordingly, in the present work, an attempt was made to change the medium of the interface at the target drilling zone through application of seven different surface precursors to influence the local heat-flow characteristics. The cracking behavior of the soda lime glass during microwave drilling in a customized applicator under controlled power input (90–900 W) at 2.45 GHz was investigated. The heat was generated inside the applicator by creating a plasma sphere in the drilling zone through a metallic concentrator. The thermal shock on the glass specimen was found reduced by the combination of a good dielectric precursor and microwave concentration for hotspot formation, which in turn, reduces the cracking/crazing tendency. Trials were carried out while drilling holes on 1.2 mm thick glass plates at various duty cycles (DCs) to study the crack intensity and pattern. The near-field microwave drilling condition was also simulated to obtain the contours of the induced stresses. The results so obtained were compared with the cracking signatures of the experimental outputs; a good correlation could be obtained. It was found that both solid and liquid fluxes as precursor could be effective to control cracking during microwave drilling.
Trauma in silico: Individual-specific mathematical models and virtual clinical populations
Authors: Brown David , Namas Rami A. , Almahmoud Khalid , Zaaqoq Akram , Sarkar Joydeep , Barclay Derek A. , Yin Jinling , Ghuma Ali , Abboud Andrew , Constantine Gregory , Nieman Gary , Zamora Ruben , Chang Steven C. , Billiar Timothy R. , Vodovotz Yoram
Published: April 2015

A mathematical model of the human response to trauma replicates individual patient outcomes but predicts unexpected results in populations.
Renal denervation: Not as easy as it looks
Authors: Esler Murray
Published: April 2015

Renal sympathetic denervation in hypertensive patients is less effective than anticipated, owing to radio frequency energy being applied to a part of the renal artery where the nerves are at the greatest distance from the aortic lumen, and to distortion of energy distribution and temperature gradients by regional tissue anatomical variations (Tzafriri
et al
., this issue).
Transforming training to reflect the workforce
Authors: Mathur Ambika , Meyers Frederick J. , Chalkley Roger , O’Brien Theresa C. , Fuhrmann Cynthia N.
Published: April 2015

Twenty-first century training programs seek to provide the “BEST” graduate education for our future biomedical workforce.
Sleep well, breathe well, age well
Authors: Ju Yo-El
Published: April 2015

Sleep-disordered breathing hastens cognitive decline by a decade, but positive airway pressure treatment may offset this effect.