Nanopore translocation reveals electrophoretic force on A- and B-form nucleic acids.

Electrophoretic transport plays a pivotal role in advancing sensing technologies, with A-form nucleic acids, predominantly RNA-containing, emerging as the new frontier for nanopore sensing and sequencing. Here, we compare the less-explored dynamics of A-form electrophoretic transport with the well-researched transport of B-form DNA. Using DNA/RNA nanotechnology and solid-state nanopores, the translocation of RNA:DNA (RD) and DNA:DNA (DD) duplexes was examined. Notably, RD duplexes were found to translocate through nanopores up to 1.8 times faster than DD duplexes, despite containing the same number of base pairs. Our experiments reveal that A- and B-form duplex molecules with the same contour length move with comparable velocity through nanopores. We examined the physical characteristics of both duplex forms using atomic force microscopy, agarose gel electrophoresis, and dynamic light scattering measurements. With the help of coarse-grained and atomistic molecular dynamics simulations, we find the effective force applied by the electric field to a fragment of A-form or B-form duplex in a nanopore to be approximately the same. Our results shed light on the significance of helical form in nucleic acid translocation, with implications for RNA sensing, sequencing, and molecular understanding of electrophoretic transport.

Close encounters with DNA.

Over the past ten years, the all-atom molecular dynamics method has grown in the scale of both systems and processes amenable to it and in its ability to make quantitative predictions about the behavior of experimental systems. The field of computational DNA research is no exception, witnessing a dramatic increase in the size of systems simulated with atomic resolution, the duration of individual simulations and the realism of the simulation outcomes. In this topical review, we describe the hallmark physical properties of DNA from the perspective of all-atom simulations. We demonstrate the amazing ability of such simulations to reveal the microscopic physical origins of experimentally observed phenomena. We also discuss the frustrating limitations associated with imperfections of present atomic force fields and inadequate sampling. The review is focused on the following four physical properties of DNA: effective electric charge, response to an external mechanical force, interaction with other DNA molecules and behavior in an external electric field.

Methodology and feasibility of a home-based examination in disabled older women: the Women's Health and Aging Study.

BACKGROUND: To ascertain disease and functional capacity in community-resident disabled older women in the Women's Health and Aging Study (WHAS), a prospective investigation of the causes and course of disability, a home-based standardized physical examination and performance test battery were developed. Thirty-nine tests were administered, 9 by a lay interviewer and 30 by a nurse. This scope and intensity of testing had not been performed previously in a home environment or on such a functionally limited population. Thus, substantial developmental work was required. This report describes the administrative procedures and field experience for each exam component, highlighting innovations pertinent to home administration. METHODS: Exclusion criteria, safety issues, administration time, completion rates, and reasons for incomplete data are reported. Administration time is based on 30 exams conducted over a 3-week period 90% of the way through baseline data collection. Completion status was determined using all 1,002 participants and is categorized as follows: complete; partial; not done, health; not done, other; and refused. RESULTS: Seventy-two percent of the screened, eligible respondents completed the 30-min interviewer-administered physical assessment and the 2-hr, 10-min nurse examination. Classifiable data were obtained for 90% of participants on 36 examination items. Lower completion rates were obtained on the other three tests primarily due to exclusions for health-related conditions; environmental constraints and participant refusal were minimal. CONCLUSION: Extensive, research-oriented physical evaluation can be successfully and safely performed in a home setting. In future studies, home-based examination may be preferable, as participation in the WHAS examination substantially exceeded rates for clinic-based exams in similar populations.

Self-perceived unmet health care needs of persons enrolled in HIV care.

We examined the prevalence of, and factors associated with unmet health service needs among persons with HIV disease. Data were examined from 1,851 participants in the U.S. AIDS Cost and Service Utilization Study, drawn from 26 medical care providers in 10 cities. Geographic areas with large numbers of AIDS cases, and health care providers within them were chosen as study sites. After completing a screener questionnaire, potential participants at each site were stratifed by illness stage, HIV exposure route, and insurance status; a systematic random sample within those strata were selected for the study. Participants completed a comprehensive survey of HIV-related service use and costs, which also asked them to identify unmet health service needs. Analyses identified the relationship between unmet needs and: stage of illness, type of insurance, source of care, living arrangement, and AIDS prevalence of respondents' geographic region. At least one unmet need was reported by 20% of the sample. Needs for non-institutional services, e.g, dental care, mental health, and medications were more likely to be unmet than need for emergency room and hospital care. While most factors significantly affected the odds of having an unmet need, the greatest effects were found for private insurance and HIV asymptomatic status, both of which decreased the odds of unmet needs by approximately 50%. These findings suggest that insurance coverage for services required during the chronic phase of HIV illness is inadequate and should be augmented.

The impact of housing status on health care utilization among persons with HIV disease.

This study sought to identify the prevalence of unstable housing situations, and for whom they occurred, and to examine differences in health care utilization by housing status. Housing status and inpatient and outpatient health care utilization of 1,851 HIV-infected individuals was ascertained through interviews. Nine percent of respondents were in unstable housing situations. Unstable housing was associated with significantly lower functional status. The unstably housed were more likely to visit an emergency room (p < 0.05) and had fewer ambulatory visits than persons with stable housing (p < 0.03). They incurred nearly five more hospital days and their average hospitalization was approximately 1.5 days longer than the stably housed, although these differences were not significant. Utilization of ambulatory care is lower among unstably housed persons with HIV disease, which may have led to their increased reliance upon emergency rooms and hospitals. Helping HIV-infected individuals maintain adequate housing could reverse this pattern.

Results of the ACSUS for pediatric AIDS patients: utilization of services, functional status, and social severity.

OBJECTIVE: This study describes demographic characteristics of pediatric AIDS patients, describes hospital and community-based service utilization patterns, and analyzes medical and social support service usage patterns with respect to patient demographic characteristics, clinical trial participation, functional/developmental status, and social environment. DATA SOURCES AND STUDY SETTING: Data reported in this study are from the AIDS Costs and Service Utilization Survey (ACSUS) and cover the six-month period beginning March 1991 (N = 135). Pediatric patients who sought care for HIV-related problems were sampled at seven different hospitals in five metropolitan regions of the United States. All of the participating hospitals had clinics specifically serving pediatric patients infected with HIV. The sample consists of HIV-positive patients who had had at least one HIV-related symptom or condition. STUDY DESIGN: A stratified probability sample design guided the sampling strategy, which included oversampling in two large hospitals from two of the five metropolitan areas. Survey data cover an 18-month time period of health care utilization, cost, and financing information from HIV-infected patients and their providers. Utilization measures are standardized to a six-month period. Per capita income, family structure, informal personal network, functional status, and clinical trial participation are tested for associations with patterns of utilization. In addition, a weighted ten-point social severity scale was developed to assess family/household stability. DATA COLLECTION: Data were collected through a screener instrument completed by the person accompanying the child to a hospital clinic visit (usually a a parent), and through two interviews conducted in person with the patients' primary caregivers. Data from the questionnaires were coded and assembled into computerized SAS analysis files by WESTAT: PRINCIPAL FINDINGS: Children in this sample are 62 percent African American, 25 percent Hispanic, and 10 percent White. Medicaid is the primary payer for 92 percent. Mean per capita income is $3,440. Fewer than one-half (41 percent) of the families of the children receive Aid to Families with Dependent Children (AFDC). (AFDC). Within the six-month period, approximately one-third of the sample (29.6 percent) was hospitalized. Mean length of stay was 16.0 days. Clinical trial participation was positively related to mean number of hospital clinic visits and receipt of formal (paid) home care. There were no differences in use of community clinic, mental health, and inpatient facilities by clinical trial status. Participation in clinical trials was positively related to income and negatively related to social severity. In four cities, emergency room use was consistently lower for clinical trial participants than for nonparticipants. CONCLUSIONS: Data from the first six months of the ACSUS pediatric sample suggest that participation in clinical trials may bring about access to social services that appear to reduce emergency room use. However, the findings reported here are descriptive and exploratory. Further multivariate, nonparametric analyses of the full 18-month provider-patient merged data set are necessary to confirm the simple correlations found in this study.

Measurement of coffee and caffeine intake: implications for epidemiologic research.

Reported associations between coffee or caffeine intake and benign breast disease, cancers, and cardiovascular diseases have generally been weak and inconsistent. The apparent discrepancies in these studies might be attributable to imprecision in the measurement of coffee and caffeine intake. A study of a random sample of 2,714 U.S. adults disclosed considerable misclassification of total caffeine intake and, to a lesser extent, coffee intake when the estimates were limited to only the number of cups of coffee consumed. Adjustment for the following factors is recommended: amount of caffeinated and decaffeinated coffee consumed both on weekdays and on weekends; the size of the container used; the method used to brew caffeinated coffee; and the amount of caffeine imbibed from tea and soft drinks. Intake of coffee varied markedly between seasons of the year and over time. Random misclassification of coffee and caffeine intake would have the effect of obscuring dose-response relationships to disease incidence.

Confounders contributing to the reported associations of coffee or caffeine with disease.

The role of caffeine or coffee in causing or promoting the incidence of serious disease is equivocal. Two design factors may account for the discrepancies in reported findings on the effects of coffee drinking: (a) imprecision of measurement and (b) confounding variables. A study of 2,714 white U.S. adults disclosed that, of 32 risk factors analyzed by linear and logistic regression, only sex and cigarette smoking were found to be important potential confounders of caffeine and coffee intake. Partial R2 values of the other 30 risk factors were relatively small and were inconsistent for each sex. It is unlikely that any of these factors could explain any of the reported associations between caffeine or coffee consumption and certain diseases. However, certain weak associations with caffeine or coffee intake should be included in the study design when they are known to be risk factors of a disease under investigation. These factors for men are dietary fat intake, vitamin C intake, and body mass index; and for women are vitamin use, alcohol intake, stress, and perceived health status.

Critical analysis of the preoperative and operative predictors of aortocoronary bypass patency.

A prospective analysis of the angiographic and operative anatomic and reconstructive variables that influenced graft patency was undertaken at the University of Virginia Medical Center in 50 consecutive patients. Postoperative restudy showed that 18 of the 168 grafts performed were occluded due to venous disease, inadequate run-off, or sequential design error. Angiographic artery size was 27% larger than operative estimations; graft patency significantly increased with increasing distal artery diameter, with decreasing venous conduit diameter, and with good graftability rating of the vessels preoperatively. Ejection fraction, the degree of arterial stenosis, and the source of the saphenous vein conduit (the thigh or the lower leg) had no influence on graft patency. Simple grafts had a 96% patency, while sequential grafts had an 80% patency. When design error for sequential grafts was eliminated, the sequential patency rate rose to 88%. For revascularization of small circumflex vessels, consideration should be given to variation in the sequential grafting technique to improve patency in these vessels.

Optimal flow pattern for mechanical ventilation of the lungs. 2. The effect of a sine versus square wave flow pattern with and without an end-inspiratory pause on patients.

In four series of patients, the efficiency of ventilation of a sine wave without an end-inspiratory pause was compared to a square wave without a pause, a sine wave with a pause to a square wave with a pause, a sine wave to a sine wave with a pause, and a sine wave with a long pause to one with a short pause. The primary mode of evaluation was through simultaneous airway and arterial argon washout curves. Additional cardiopulmonary measurements were made. Results indicate: (1) a statistically significant improvement in ventilation with a sine wave with a pause; (2) a statistically significant improvement with the longer pause as compared to the short pause.

The strength of metal reinforced methylmethacrylate fixation of pathologic fractures.

Fixation of the pathological fracture in terminal patients has in the past added the trauma of an extensive surgical procedure to an already weakened patient. Intramedullary fixation with single and double rods in conjuction with polymethylmethacrylate have been compared to ascertain the effect of different loading conditions using torque and analysis under compression measurements of the strength of repair bone. Extensive intramedullary reaming can be avoided with polymethylmethacrylate. The cement effectively transmits the load from the proximal to the distal fragment. The single large rod method would be more desirable for stiffer bones while the double thin rod technique may be applicable to more flexible bones.

Regulation of intracranial pressure in rat, dog, and man.

Intracranial resistance and compliance were assessed in the cerebrospinal fluid system of rat, dog, and man by means of low-volume, short-duration infusions of artificial CSF into the subarachnoid space. A family of pressure/time response curves was obtained for each species: at low flow rates, steady-state pressure elevations were associated with normal neurological function; at high flow rates, rapid linear pressure elevations were associated with marked neurological dysfunction. From these curves a mathematical model was developed which describes transport and pressure-dependent valvelike characteristics of the CSF outflow resistance. This resistance shows a progressive phylogenetic change in rat, dog, and man which increasingly enhances the species' abilities to vent fluid from the intracranial cavity into the venous circulation. Arachnoid villi appear to be the major structures modulating sustained, nonlethal elevations of intracranial pressure.

Intracranial pressure regulation: a comparative model of cerebrospinal fluid systems.

A comparative model of the cerebrospinal fluid (CSF) system in rat, dog and man was derived from manometric data using low volume, short duration infusions into the subarchanoid space in order to describe the mechanisms governing intracranial pressure dynamics. The mathematical model indicates that steady-state elevations of intracranial pressure are regulated primarily by a nonlinear, pressure dependent outflow resistance to CSF reabsorption. While the form of the resistance relationship is similar for the three species tested, differences in the magnitude of CSF outflow parameters are apparent. Model stimulation on a digital computer suggests that parameter changes within the resistance relationship can have a profound effect on the intracranial pressure. In contrast, intracranial compliance acts only to buffer transient changes in volume prior to the establishment of steady-state CSF pressures.