Acute CO2 tolerance in fishes is associated with air breathing but not the Root effect, red cell ßNHE, or habitat.

High CO2 (hypercapnia) can impose significant physiological challenges associated with acid-base regulation in fishes, impairing whole animal performance and survival. Unlike other environmental conditions such as temperature and O2, the acute CO2 tolerance thresholds of fishes are not understood. While some fish species are highly tolerant, the extent of acute CO2 tolerance and the associated physiological and ecological traits remain largely unknown. To investigate this, we used a recently developed ramping assay, termed the Carbon Dioxide maximum (CDmax), that increases CO2 exposure until loss of equilibrium (LOE) is observed. We investigated if there was a relationship between CO2 tolerance and the Root effect, ß-adrenergic sodium proton exchanger (ßNHE), air-breathing, and fish habitat in 17 species. We hypothesized that CO2 tolerance would be higher in fishes that lack both a Root effect and ßNHE, breathe air, and reside in tropical habitats. Our results showed that CDmax ranged from 2.7 to 26.7 kPa, while LOE was never reached in four species at the maximum PCO2 we could measure (26.7 kPa); CO2 tolerance was only associated with air-breathing, but not the presence of a Root effect or a red blood cell (RBC) ßNHE, or fish habitat. This study demonstrates that the diverse group of fishes investigated here are incredibly tolerant of CO2 and that although this tolerance is associated with air-breathing, further investigations are required to understand the basis for CO2 tolerance.

Preferential intracellular pH regulation is a common trait amongst fishes exposed to high environmental CO2.

Acute (<96 h) exposure to elevated environmental CO2 (hypercarbia) induces a pH disturbance in fishes that is often compensated by concurrent recovery of intracellular and extracellular pH (pHi and pHe, respectively; coupled pH regulation). However, coupled pH regulation may be limited at CO2 partial pressure (PCO2 ) tensions far below levels that some fishes naturally encounter. Previously, four hypercarbia-tolerant fishes had been shown to completely and rapidly regulate heart, brain, liver and white muscle pHi during acute exposure to >4 kPa PCO2  (preferential pHi regulation) before pHe compensation was observed. Here, we test the hypothesis that preferential pHi regulation is a widespread strategy of acid-base regulation among fish by measuring pHi regulation in 10 different fish species that are broadly phylogenetically separated, spanning six orders, eight families and 10 genera. Contrary to previous views, we show that preferential pHi regulation is the most common strategy for acid-base regulation within these fishes during exposure to severe acute hypercarbia and that this strategy is associated with increased hypercarbia tolerance. This suggests that preferential pHi regulation may confer tolerance to the respiratory acidosis associated with hypercarbia, and we propose that it is an exaptation that facilitated key evolutionary transitions in vertebrate evolution, such as the evolution of air breathing.

The effect of substrate rearing on growth, aerobic scope and physiology of larval white sturgeon Acipenser transmontanus.

The effect of substratum on growth and metabolic rate was assessed in larval white sturgeon Acipenser transmontanus. Yolk-sac larvae (YSL) were reared in bare tanks or tanks with gravel as substratum from hatch until approximately 16 days post hatch (dph). The effect of an artificial substratum was also evaluated on growth alone. Substratum had a significant effect on mass, with larvae reared in gravel and artificial substrata being larger than those reared without substratum. Routine metabolic rates were significantly lower and relative aerobic scope (the difference between maximum and routine metabolic rate) was significantly higher for YSL and feeding larvae (FL) reared in gravel relative to those reared in bare tanks, particularly before fish started feeding exogenously. Furthermore, gravel-reared larvae had higher whole-body glycogen concentrations relative to bare-tank-reared larvae. Routine factorial scope (maximum metabolic rate divided by routine metabolic rate) was relatively low in all treatments (< 1·7) indicating a limited ability to elevate metabolic rate above routine early in development and mass exponents for metabolic rate exceeded 1. Taken together, these data indicate that YSL reared without substratum may divert more of their energy to non-growth related processes impairing growth. This finding underscores the importance of adequate rearing substratum for growth of A. transmontanus and may provide support for habitat restoration and alternative hatchery rearing methods associated with sturgeon conservation.

Development of an electronic medical record based intervention to improve medical care of osteoporosis.

UNLABELLED: Osteoporosis is infrequently addressed during hospitalization for osteoporotic fractures. An EMR-based intervention (osteoporosis order set) was developed with physician and patient input. There was a trend toward greater calcium supplementation from July 2008 to April 2009 (s = 0.058); however, use of antiresorptives (13%) or discharge instructions for BMD testing and osteoporosis treatment (10%) remained low. INTRODUCTION: Osteoporosis is infrequently addressed during hospitalization for osteoporotic fractures. The study population consisted of patients over 50 years of age. METHODS: Northwestern Memorial Hospital is a tertiary care academic hospital in Chicago. This study was conducted from September 1, 2007 through June 30, 2009. RESULTS: Physicians reported that barriers to care comprised nonacute nature of osteoporosis, belief that osteoporosis should be addressed by the PCP, low awareness of recurrent fractures, and radiographs with terms such as "compression deformity", "wedge deformity", or "vertebral height loss" which in their opinion were not clearly indicative of vertebral fractures. An EMR-based intervention was developed with physician and patient input. Over the evaluation period, 295 fracture cases in individuals over the age of 50 years in the medicine floors were analyzed. Mean age was 72 ± 11 years; 74% were female. Sites of fracture included hip n = 78 (27%), vertebral n = 87 (30%), lower extremity n = 61 (21%), upper extremity n = 43 (15%) and pelvis n = 26 (9%). There was no increase in documentation of osteoporosis in the medical record from pre- to post-EMR implementation (p = 0.89). There was a trend toward greater calcium supplementation from July 2008 to April 2009 (p = 0.058); however, use of antiresorptives (13%) or discharge instructions for BMD testing and osteoporosis treatment (10%) remained low. CONCLUSION: An electronic medical record intervention without electronic reminders created with physician input achieves an increase in calcium supplementation but fails to increase diagnosis or treatment for osteoporosis at the time of hospitalization for a fragility fracture.

X-ray fabric analysis of hot-worked and annealed flint.

Two specimens of flint described by Green have been subjected to intensive x-ray fabric analysis. The specimen compressed in the beta-quartz field recrystallized to a fabric with a strong maximum of c-axes parallel to the direction of compression and a weaker equatorial concentration perpendicular to the axis of compression. Annealing of a similar specimen eliminated the equatorial concentration and strengthened the axial concentration six- to eightfold. In the latter specimen, the fabric determined by x-ray analysis agrees closely with Green's optically measured fabric. It is possible to obtain c-axis fabrics directly from the very weak 0003 diffraction peak.

Structural study of K(x)Na(1 - x)NbO(3) (KNN) for compositions in the range x = 0.24-0.36.

The structure of the A-site substituted perovskite K(x)Na(1 - x)NbO(3), x = 0.24-0.36, where a phase boundary was previously reported, has been determined by high-resolution X-ray powder and neutron powder diffraction studies. The structure of the x = 0.3 compound was refined in the monoclinic space group Pm at 293 K and in P4mm at 523 K. The Glazer tilt system of the room-temperature monoclinic phase is a(0)b(+)c(0), which has implications for the nature of the next symmetry change with composition towards pure potassium niobate. A phase-coexistence region at the transition between monoclinic and tetragonal phases was also identified, consistent with a first-order phase boundary. There is also evidence for an intermediate oxygen-octahedra tilted tetragonal phase.

A validation of intracellular pH measurements in fish exposed to hypercarbia: the effect of duration of tissue storage and efficacy of the metabolic inhibitor tissue homogenate method.

This study assessed the effect of tissue storage duration and accuracy of the metabolic inhibitor tissue homogenate (MITH) method on intracellular pH (pHi) values of tissues of white sturgeon Acipenser transmontanus during hypercarbia. No effect of storage in liquid nitrogen of up to 30 days was observed and MITH appears appropriate for measurement of pH in fish exposed to up to 10% CO2 (10000 Pa pCO2).

Health insurance and access to care for symptomatic conditions.

BACKGROUND: The uninsured receive less medical care than the insured. However, it is not known whether the uninsured are less likely to seek medical care for highly "serious" or "morbid" symptoms. METHODS: Participants in the National Access to Care Survey were asked whether they had experienced any of 15 highly serious or morbid symptoms. Those who did were asked whether they received medical care and, if care was not received, whether care was thought to have been necessary. RESULTS: A total of 574 respondents (16.4%) reported 794 new serious or morbid symptoms. Of these, 499 people (86.9%) had health insurance, and they reported 691 new symptoms; 75 (13.1%) lacked health insurance, and they reported 103 symptoms. The uninsured were less likely to have received medical care and more likely to say they did not receive care even though they thought it was needed (P = .001). Medical care was received for 45.4% of symptoms for the insured and 24.3% for the uninsured; care was not thought to have been needed for 41.0% of symptoms for the insured and 45.6% for the uninsured; and care was thought necessary but was not received for 13.6% of symptoms for the insured and 30.1% for the uninsured. In multivariate analysis, the uninsured were much less likely to have received care than the insured (adjusted odds ratio, 0.43; 95% confidence interval, 0.23-0.81). CONCLUSION: Lack of health insurance is a major barrier to receiving medical care, even for highly serious and morbid symptoms.

Relationship of functional health literacy to patients' knowledge of their chronic disease. A study of patients with hypertension and diabetes.

BACKGROUND: Inadequate functional health literacy is common, but its impact on patients with chronic diseases is not well described. OBJECTIVE: To examine among patients with hypertension or diabetes the relationship between their functional health literacy level and their knowledge of their chronic disease and treatment. METHODS: We conducted a cross-sectional survey of patients with hypertension and diabetes presenting to the general medicine clinics at 2 urban public hospitals. Literacy was measured by the Test of Functional Health Literacy in Adults. Knowledge of their illness was assessed in patients with diabetes or hypertension using 21 hypertension and 10 diabetes questions based on key elements in educational materials used in our clinics. RESULTS: A total of 402 patients with hypertension and 114 patients with diabetes were enrolled. Mean (+/- SD) knowledge scores for patients with hypertension with inadequate (n = 189), marginal (n = 49), or adequate (n = 155) literacy were 13.2 +/- 3.1, 15.3 +/- 2.2, and 16.5 +/- 2.3, respectively (range, 4-20; P < .001). A total of 92% of patients with hypertension and adequate literacy levels knew that a blood pressure reading of 160/100 mm Hg was high compared with 55% of those in the lowest reading level (P < .001). Mean (+/- SD) knowledge scores for patients with diabetes with inadequate (n = 50), marginal (n = 13), or adequate (n = 51) literacy were 5.8 +/- 2.1, 6.8 +/- 1.9, and 8.1 +/- 1.6, respectively (range, 1-10; P < .001). A total of 94% of patients with diabetes and adequate functional health literacy knew the symptoms of hypoglycemia compared with 50% of those with inadequate literacy (P < .001). CONCLUSIONS: Inadequate functional health literacy poses a major barrier to educating patients with chronic diseases, and current efforts to overcome this appear unsuccessful.

Juvenile atlantic and shortnose sturgeons (family: Acipenseridae) have different hematological responses to acute environmental hypoxia.

Experiments were conducted to determine the behavioral and physiological responses to acute hypoxic challenges in Atlantic (Acipenser oxyrinchus) and shortnose (Acipenser brevirostrum) sturgeons. We measured the ventilatory rate following a 45-mmHg hypoxic challenge, as well as a variety of hematological parameters, including O2 transport and hormonal, ionic, and metabolic variables, following a 1-h exposure to either 75- or 30-mmHg hypoxic challenges. Compared to fish in normoxic conditions (Pwo2 150 mmHg), juveniles of both species increased their ventilatory rate by approximately 40% when exposed to a 1-h challenge at 45 mmHg Pwo2. Hematological variables (e.g., hematocrit, hemoglobin, and Na+ and Cl- levels) did not change substantially following a 1-h challenge at 75 mmHg Pwo2. Conversely, a severe hypoxic challenge of 30 mmHg caused changes in several hematological variables (e.g., whole blood glucose and plasma cortisol and lactate levels). Most of these hematological parameters returned to prehypoxic levels within 2 h. Severe environmental hypoxia elicited the same basic pattern of response in both species; however, maximal plasma lactate levels were higher in Atlantic sturgeons, and maximal cortisol levels were higher in shortnose sturgeons. Whether these species differences are related to dissimilar hypoxia-tolerance, ecological, and/or endocrinological characteristics between these two species is not entirely clear.

Pulsed Doppler echocardiography: principles and applications.

A new recording and display system is described for use with pulsed Doppler blood flow velocity detectors in the diagnosis of valvular and septal defects. The principles of the pulsed Doppler device are described along with the methods used to analyze and display the Doppler shifted signal from flow jets resulting from various valve defects. An M-mode display is combined with blood flow display to provide a convenient record of the clinical procedure. Examples of aortic stenosis, aortic insufficiency, mitral stenosis and regurgitation are presented along with signals from other valves.

Doppler echocardiography: applications, limitations and future directions.

On the basis of principles that are similar to (but differ slightly from) those that underlie M mode and two dimensional techniques, pulsed Doppler echocardiography permits evaluation of intracardiac blood flow noninvasively. This technique is helpful in the diagnosis and management of patients with valvular and congenital heart disease, and in some circumstances provides information not available from M mode or two dimensional imaging. Despite several notable limitations, pulsed Doppler echocardiography is a useful diagnostic technique whose clinical application is likely to increase as future technologic improvements occur.

Inadequate literacy is a barrier to asthma knowledge and self-care.

STUDY OBJECTIVES: To determine the relationship of literacy to asthma knowledge and ability to use a metered-dose inhaler (MDI) among patients with asthma. DESIGN: Cross-sectional survey. SETTING: Emergency department and asthma clinic at an urban public hospital. PATIENTS: Convenience sample of 273 patients presenting to the emergency department for an asthma exacerbation and 210 patients presenting to a specialized asthma clinic for routine care. INTERVENTIONS: Measurement of literacy with the Rapid Estimate of Adult Literacy in Medicine, asthma knowledge (20 question oral test), and demonstration of MDI technique (six-item assessment). MEASUREMENTS AND RESULTS: Only 27% of patients read at the high-school level, although two thirds reported being high-school graduates; 33% read at the seventh- to eighth-grade level, 27% at the fourth- to sixth-grade level, and 13% at or below the third-grade level. Mean asthma knowledge scores (+/-SD) were directly related to reading levels: 15.1+/-2.5, 13.9+/-2.5, 13.4+/-2.8, 11.9+/-2.5, respectively (p < 0.01). Patient reading level was the strongest predictor of asthma knowledge score in multivariate analysis. Poor MDI technique (< or =3 correct steps) was found in 89% of patients reading at less than the third-grade level compared with 48% of patients reading at the high-school level. In multivariate regression analyses, reading level was the strongest predictor of MDI technique. CONCLUSIONS: Inadequate literacy was common and strongly correlated with poorer knowledge of asthma and improper MDI use.

Reading skills and family planning knowledge and practices in a low-income managed-care population.

OBJECTIVE: To examine the relationship between reading ability and family planning knowledge and practices among Medicaid managed care enrollees. METHODS: A total of 406 women age 19-45 years enrolled in TennCare and members of Prudential HealthCare Community Plan in Memphis, Tennessee were interviewed to determine their methods of contraception, desire for additional information about contraceptives, and knowledge about the time in menstrual cycle they are at highest risk for pregnancy. Patient reading ability was assessed by an abbreviated version of the Test of Functional Health Literacy of Adults. The independent associations between reading ability, desire for additional contraceptive information, and knowledge about the highest risk time for pregnancy were assessed with logistic regression. RESULTS: Almost 10% of the respondents had low reading skills. Women who had used an intrauterine device, douching, rhythm, or levonorgestrel implants as methods of birth control had higher rates of low reading skills than women who used other methods of birth control. Compared with women with good reading skills, women with low reading skills were 2.2 times (95% confidence interval [CI] 1.1, 4.4) more likely to want to know more about birth control methods and 4.4 times (95% CI 2.2, 9.0) more likely to have incorrect knowledge about when they were most likely to get pregnant. These relationships were significant even after controlling for age, race, and marital status. CONCLUSION: Health providers and organizations that serve historically underserved populations must understand that some individuals have a low level of reading ability that limits family planning education.

Literacy and contraception: exploring the link.

OBJECTIVE: To describe what is known about the relation of literacy skills to contraceptive use and to suggest directions for future research. An overview of what is known about the literacy skills of Americans and the prevalence of inadequate functional health literacy is presented. Information about reading requirements for various methods of contraception and advice from health educators on dealing with low-literate populations are described. DATA SOURCES: MEDLINE, PsychInfo, and ERIC searches for the last 20 years were completed using the terms literacy, literacy and health, family planning, health status, educational status, risk factors, contraception, and pregnancy. METHODS OF STUDY SELECTION: The primary literature searches identified 125 articles. After reviewing abstracts for these articles, we excluded 79, because they contained no specific mention of literacy or educational status relating to contraception. TABULATION INTEGRATION, AND RESULTS: We were unable to identify and study specifically devoted to the relation between functional literacy and actual use of contraceptives. Forty-six with relevant background or related information were identified: literacy and health (19), adult literacy (nine), literacy and contraception (11), and literacy and family planning (seven). Over one-third of English-speaking and 62% of Spanish-speaking patients had inadequate or marginal functional health literacy in a study conducted at two urban public hospitals. Studies by health educators have demonstrated that information for many types of contraceptives is frequently above the patient's reading level. Available epidemiologic information on the relation between educational status and unplanned pregnancy is also presented. CONCLUSIONS: Although no study has specifically addressed how functional health literacy affects contraceptive use, it is reasonable to hypothesize that functional health literacy influences contraceptive knowledge, attitudes, and behaviors. Future research should focus on the relation between functional health literacy and actual use of various contraceptives.

Limited English proficiency and Latinos' use of physician services.

Many Latinos have limited English proficiency and this may negatively affect their use of health care services. To examine this, the authors interviewed 465 Spanish-speaking Latinos and 259 English speakers of various ethnicities who presented to a public hospital emergency department with non-urgent medical problems to assess previous physician visits, sociodemographic characteristics, and level of English proficiency. The proportion of patients who reported no physician visit during the 3 months before study enrollment was not related to English proficiency. However, among the 414 patients who saw a physician at least once, Latinos with fair and poor English proficiency reported approximately 22 percent fewer physician visits (p = 0.020 and p = 0.015, respectively) than non-Latinos whose native language was English, even after adjusting for other determinants of physician visits. The magnitude of the association between limited English proficiency and number of physician visits was similar to that for having poor health, no health insurance, or no regular source of care.

Relationships between in-hospital and 30-day standardized hospital mortality: implications for profiling hospitals.

OBJECTIVE: To examine the relationship of in-hospital and 30-day mortality rates and the association between in-hospital mortality and hospital discharge practices. DATA SOURCES/STUDY SETTING: A secondary analysis of data for 13,834 patients with congestive heart failure who were admitted to 30 hospitals in northeast Ohio in 1992-1994. DESIGN: A retrospective cohort study was conducted. DATA COLLECTION: Demographic and clinical data were collected from patients' medical records and were used to develop multivariable models that estimated the risk of in-hospital and 30-day (post-admission) mortality. Standardized mortality ratios (SMRs) for in-hospital and 30-day mortality were determined by dividing observed death rates by predicted death rates. PRINCIPAL FINDINGS: In-hospital SMRs ranged from 0.54 to 1.42, and six hospitals were classified as statistical outliers (p <.05); 30-day SMRs ranged from 0.63 to 1.73, and seven hospitals were outliers. Although the correlation between in-hospital SMRs and 30-day SMRs was substantial (R = 0.78, p < .001), outlier status changed for seven of the 30 hospitals. Nonetheless, changes in outlier status reflected relatively small differences between in-hospital and 30-day SMRs. Rates of discharge to nursing homes or other inpatient facilities varied from 5.4 percent to 34.2 percent across hospitals. However, relationships between discharge rates to such facilities and in-hospital SMRs (R = 0.08; p = .65) and early post-discharge mortality rates (R = 0.23; p = .21) were not significant. CONCLUSIONS: SMRs based on in-hospital and 30-day mortality were relatively similar, although classification of hospitals as statistical outliers often differed. However, there was no evidence that in-hospital SMRs were biased by differences in post-discharge mortality or discharge practices.

Is the P25L a "real" VHL mutation?

BACKGROUND: The von Hippel-Lindau (VHL) gene has two translational initiation sites separated by 53 codons. Both proteins have been detected in cells and have equivalent activity. A mutation in the first 53 codons of the open reading frame has no effect on the structure of the smaller protein. As expected, the vast majority of VHL mutations are downstream of the second initiation site and alter both proteins. However, several candidate mutations have been found in the first 53 codons, including a substitution of leucine for proline at position 25 (P25L) of the larger protein. METHODS AND RESULTS: DNA sequence analysis showed two VHL gene mutations, P25L and P86R, in an individual with a clinical diagnosis of VHL disease. Both mutations have been reported previously. P25L alters only the upstream protein, whereas P86R alters both VHL proteins. Based on the positions of the mutations, P86R is more likely to be pathogenically significant than the P25L mutation. A survey of anonymized DNAs for P25L, using allele-specific PCR, revealed that it is a variant with an allele frequency of approximately 0.5%. CONCLUSION: P25L is a rare variant of the VHL gene and cannot be considered a cause of VHL disease. However, this work does not prove that P25L is entirely innocuous.

A revised measure of symptom-specific health care use.

The objective was to determine physicians' ratings of the clinical importance of common adult symptoms and to use these ratings to develop a new measure of symptom-specific use of health care services. We developed a list of common symptoms using the National Ambulatory Medical Care survey. We surveyed a random sample of internists, family physicians, general practitioners and emergency medicine physicians from the American Medical Association's Physician Masterfile and asked them to rate symptoms' seriousness, impact on quality of life and urgency of need for medical attention. The symptoms' prevalences were determined in a general population survey (National Access to Care Survey). Eleven items were classified as "serious" (median seriousness ratings of 7 or higher on scale from 1 to 10); most of these also were judged to have high impact on quality of life. Another 12 items that were not judged "serious" had median quality of life impact scores of 7 or higher and were classified as "morbid". Sixteen items did not meet criteria for either "serious" or "morbid" symptoms and were classified as "intermediate". Six other items had median seriousness and quality of life impact scores of 3 or less and were classified as "benign". A total of 24 of these items (7 "serious", 8 "morbid", 8 "intermediate" and 1 "benign") were selected to form the symptom-response measure. In the national survey, 26.3% reported one or more serious symptom, 30.6% reported one or more morbid symptom and 29.6% reported one or more intermediate symptom. This new instrument expands on earlier "symptom-response" measures by including a larger number and a broader spectrum of symptoms. This measure should be useful to assess differences in patterns of health care use for particularly serious or morbid conditions; such variations may indicate problems with access to medical care.

Simultaneous detection of five mutations in the steroid 21-hydroxylase gene using nested allele-specific amplification.

Congenital adrenal hyperplasia due to deficiency of steroid 21-hydroxylase (CYP21) is most frequently due to mutations that arise from the nearby CYP21 pseudogene. The mechanism involves either unequal crossing over, which deletes part of the CYP21 functional gene, or gene conversion which puts a mutation from the pseudogene into the functional gene. We have devised an assay to rapidly screen for five known mutations that are due to gene conversion within an 1,800 bp region of the CYP21 gene--I172N, V281L, Q318X, R356W, and a cluster of mutations in exon 6 (I236N, V237E, M239K). This method is based on a set of nested allele-specific polymerase chain reactions done simultaneously in one tube, for which we suggest the acronym NASA, for nested allele-specific amplification. The assay is capable of detecting the mutations individually as well as all combinations of mutations tested.