How and what rural women know: experiences in Bangladesh.
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Studies suggest that saliva could be used instead of blood in the therapeutic monitoring of many drugs. This has distinct advantages in pediatrics and neonatology as saliva sampling is painless and spares blood. Stimulation of saliva secretion with a chemical stimulus (i.e. citric acid applied over the tongue) facilitates the study of younger patients. Secretory and reabsorptive processes which take place in the ductal system of the salivary glands, and the rate of flow of the secretion play major roles in the determination of the concentration of solutes in saliva. Drug passage into saliva follows the general principles of movement of drugs across biologic membranes. Only the unbound fraction of the drug in plasma is available for diffusion into saliva and a relationship exists between saliva pH and the saliva/plasma concentration ratio of many polar drugs (tolbutamide, propranolol, procainamide, etc.). However, deviations from the pH theory exist and the inter -and intra-individual variations in saliva/plasma concentration ratios of salicylate and procainamide cannot be explained solely on the basis of fluctuations of salivary pH; on the other hand, a useful relationship exists between plasma and saliva phenobarbital concentrations with no need to correct for saliva pH. The use of stimulated saliva has several advantages over resting saliva: a larger volume of the sample is obtained, the pH gradient between plasma and saliva is smaller, the variability in saliva/plasma concentration ratios of some drugs is narrowed, and less specimens are too viscous or discolored to allow drug analysis. Thorough rinsing of the mouth is required prior to saliva sampling as remnants of orally administered medicines may contaminate saliva specimens and give spuriously high values. Deviation from a simple but strict methodology accounts for some of the discrepancies found in the literature. Studies in children uniformly recommend saliva for therapeutic monitoring of phenytoin, carbamazepine and phenobarbital. Saliva sampling for therapeutic monitoring of ethosuximide, primidone and digoxin in infants and children, and of theophylline and caffeine in the neonate is promising, but little pediatric experience is available as yet. The value of saliva in therapeutic monitoring of theophylline in children is still controversial. Little of highly polar compounds such as aminoglycosides, and of polar highly protein bound drugs such as valproic acid is present in saliva. More data are still needed on the excretion of drugs in saliva in infants and in acutely ill children, and few data exist in the premature and full-term neonate.
A simple and accurate gas chromatographic method for the determination of testosterone in human urine is described. Radioactive testosterone was added to samples to correct methodological loss. A mild acid hydrolysis under protection of benzene layer gave a single estimate of testosterone glucuronate and sulphate. Paper chromatography and rechromatography on chromatoplate served for preliminary qurification. Testosterone was gas chromatographed as acetate and guantitated by the internal standard procedure and flame ionization detector. Results of control experiments, normal values for female and male subjects and estimations in patients with alterations of androgen hormone metabolism are presented.
A technique using selective inhibitors was used to estimate the relative contributions of bacterial and fungal populations to the respiration of six soils and one litter sample. The ratios of bacterial to fungal respiration in the four agricultural soils, given in percentage of the total microbial activity, ranged from 10/90 to 35/65, with the average ratio being about 30/70. In the forest soils, the ratios were 20/80 and 30/70, and in a beech litter sample, the ratio was 40/60. The fungi clearly dominated in all samples. The ratios were not found to be pH related. The difficulties which had previously limited the use of selective inhibitors for in situ soil ecological investigations, such as insufficient inhibitor specificity, inhibitor inactivation or degradation, and errors of measurement caused by elimination of competitor populations, were either resolved or methodologically avoided in the experiments. Inhibitor selectivity was demonstrated using both mixed and pure cultures of microorganisms from each soil. Through the use of experiments with short incubation periods (6-8 h), problems with population shifts and inhibitor degradation were eliminated.
Both animal experiments and certain well-established breast cancer risk factors suggest that risk to the disease is fundamentally determined by the hormones of the pituitary-gonadal axis. Although international comparisons of urinary estrogens have given support to this ypothesis, case-control studies and international comparisons of plasma estrogens and prolactin have not. Methodological problems and sampling biases probably account for the inconsistency of these investigations. Taking advantage of the known familial increased risk to breast cancer, we conducted comparative studies of teenage daughters of patients with breast cancer, including a group of girls whose mothers had bilateral breast cancer when they were less than 50 years old. The results of these studies revealed that these high-risk girls appear to have elevated levels of estrogens, prolactin, and progesterone.
One hundred and thirty-eight post-graduate students enrolled in a Diploma in Education course were tested for their ability to converse weight and volume. A methodological criticism of the earlier work or Elkind (1962) and Towler & Wheatley (1971) is offered which casts doubt on the extremely high proportion of non-conservers of volume reported in those studies. Nevertheless, using a modified version of Elkind's methodology, 18 per cent of our sample were non-conservers of volume, a result providing some support for the generaltiy of Elkind's findings. The results are discussed under the four headings of horizontal decalage, sex differences, possible effects of pre-graduate courses of study and educational implications. The importance of the individual as constructor and interpreter of his own experience is emphasized.
Simplification of radioimmunoassay procedures of urinary aldosterone-18-glucuronide was attempted, taking into consideration the aspects implied by the hydrolysis of urine and the assay itself. The procedure standardized for the hydrolysis step (samples diluted with a two-fold volume of 0.2 N HCl and incubated at 30 degrees C for 16-24 h) proved suitable in terms of practicability and accuracy. Aldosterone antisera, raised in the rabbit against an aldosterone-3-bovine albumin conjugate, were selected according to their specificity towards competing steroids. Depending on the characteristics of the antisera used, an assay of extracts, or even direct measurements of hydrolyzed urines excluding any extraction, were found to yield reliable results. In the case of a high-quality antiserum, evidence for the adequacy of assay on non-hydrolyzed urine extracts for the measurement of the excretion of unconjugated aldosterone was provided by some preliminary data. The results of the experiments, directed at the methodological and clinical validation of the simplified procedures, are reported and discussed in this paper.
INTRODUCTION: Single-cell proteomics (SCP) is entering into a transformative phase, moving beyond technically demanding benchmarking studies toward robust and reproducible workflows capable of quantifying thousands of proteins per cell. These advances highlight SCP's potential to address clinically relevant questions by resolving cellular and pathological heterogeneity that remains obscured in bulk proteomics. AREAS COVERED: This review discusses current advances, challenges, and clinical applications of SCP based on literature identified through searches in major scientific databases. Many clinically relevant samples remain underexplored in SCP studies, in part because their application requires careful evaluation of pre-analytical variables that can strongly influence proteomic readouts. Current SCP methodologies vary according to sample type, experimental conditions, and available resources. Compared with single-cell RNA sequencing, SCP remains limited in cellular throughput, making it challenging to define optimal sample sizes and to reliably detect both abundant and rare cell populations. These limitations also make dataset integration difficult, as reduced cellular coverage and sampling depth increase data sparsity. Moreover, implementing quality control strategies across sequential SCP experiments is essential to ensure data robustness, comparability, and accurate biological interpretation. EXPERT OPINION: Applying SCP to clinical samples advances our understanding of biological complexity and holds potential to drive progress in translational and precision medicine.
PURPOSE: The value of genetic information for improving the performance of clinical risk prediction models has yielded variable conclusions. Many methodological decisions have the potential to contribute to differential results. We performed multiple modeling experiments integrating clinical and demographic data from electronic health records with genetic data to understand which decisions may affect performance. METHODS: Clinical data in the form of structured diagnostic codes, medications, procedural codes, and demographics were extracted from 2 large independent health systems, and polygenic risk scores (PRS) were generated across all patients of European ancestry with genetic data in the corresponding biobanks. Crohn's disease was studied based on its substantial genetic component, established electronic health records-based definition, and sufficient prevalence for training and testing. We investigated the impact of choices regarding the PRS integration method, training sample, model complexity, and performance metrics. RESULTS: Overall, our results showed that including PRS resulted in higher performance, but this gain was only robust in situations with limited clinical information. We found consistent performance increases from more compute-intensive models, such as random forest, but the impact of other decisions varied by site. CONCLUSION: This work highlights the importance of considering methodological decision points in interpreting the impact of PRS on prediction performance in clinical models.
To be able to understand how spaceflight can affect human biology, there is a need for maximizing the amount of information that can be obtained from experiments flown to space. Recently there has been an influx of data obtained from astronauts through multi-omics approaches based on both governmental and commercial spaceflight missions. In addition to data from humans, mitochondrial specific data is gathered for other experiments from rodents and other organisms that are flown in space. This data has started to universally demonstrate that mitochondrial dysfunction is the key regulator associated with increasing health risks associated with spaceflight. This mitochondrial dysfunction can have influence downstream on immune suppression, inflammation, circadian rhythm issues, and more. Due to the space environment, standard methodologies have to be altered for performing mitochondrial specific analysis and in general sample collection for omics. To perform mitochondrial specific analysis and data collection from samples flown to space we will outline the current sample collection methods, processing of the samples, and specific analysis. Specifically we will highlight the different mitochondrial methodologies and challenges involved with research associated with spaceflight.
Cross-sectional data were analyzed for a possible relationship between household densities and physiologic alteration, based on socialization experiences with siblings in an earlier home environment. The measure of household density was persons-per-room and the measure of physiologic alteration was urinary vanillylmandelic acid. The results show an interaction between number-of-sibs and number-of-younger-sibs, with a statistically significant positive correlation between household densities and VMA values for subjects with fewer total sibs and no younger sibs, while a negative correlation was observed for subjects with one or more younger sibs. One possible interpretation of these results is that the physiologic response to crowding in humans is dependent at least in part on the earlier socialization experiences of the individual.
Gene expression profiling of single cells using single-cell and single-nucleus RNA sequencing (sxRNA-seq) enables researchers to characterize cellular heterogeneity and unraveling complex biological processes at unprecedented resolution. However, sxRNA-seq faces challenges due to the presence of ambient RNA, extraneous RNA molecules not originating from the cells of interest. Sample preparation is a major source of ambient RNA, where harsh conditions can lead to cell lysis and the release of intracellular RNA. This inescapable inclusion of ambient RNA can cause erroneous results and hinder downstream analyses. To address this issue, various methodologies have been developed to identify, quantify, and remove ambient RNA. Here, we rigorously evaluate 7 state-of-the-art methodologies for ambient RNA removal using simulated datasets, species-mixing experiments of varying complexities, and genotype-mixing experiments. We find that no single method performs the best across all datasets and metrics, but CellBender, DecontX and SoupX generally perform well.
The purpose of this study was to detect and solve apparently trivial methodological flaws in experiments of the decay type which can invalidate any fitting procedure or compartmental analysis. The problems dealt with consisted in maintaining the steady state conditions defining the "true" starting time of the efflux and its optimal duration, determining the number of exponential terms and finding how many data points are necessary to identify them. The solutions proposed include avoidance of tissue blotting prior to the efflux, running a separate non effluxed sample, stopping the washout when the log plot of remaining and effluent counts becomes parallel, use of the optimization if the correlation coefficient for curve fitting and adequate the frequency of counting to the decay rate. Errors resulting from the failure to comply with these requirements are illustrated with samples.
The interview by telephone is not an ordinary procedure to obtain investigation data. By knowing that is rarely used in Brazil, the study was planned aiming to: identify the individuals' characteristics who answer the sampled telephones; raise the interviews' statements about the operational technique and evaluate the telephone used as data collection procedure. The data indicate that most of the people who were interviewed, were females, between 30 and 40 years old and housewives. The interviewers considered between 30 and 40 years old and housewives. The interviewers considered the experience interesting, in despite of the difficulty to maintain people talking on the phone. The authors state that the interview by telephone is an efficient and fast way of bringing up data for investigation which aims to raise opinions about certain matters.
The value of genetic information for improving the performance of clinical risk prediction models has yielded variable conclusions. Many methodological decisions have the potential to contribute to differential results across studies. Here, we performed multiple modeling experiments integrating clinical and demographic data from electronic health records (EHR) and genetic data to understand which decision points may affect performance. Clinical data in the form of structured diagnostic codes, medications, procedural codes, and demographics were extracted from two large independent health systems and polygenic risk scores (PRS) were generated across all patients with genetic data in the corresponding biobanks. Crohn's disease was used as the model phenotype based on its substantial genetic component, established EHR-based definition, and sufficient prevalence for model training and testing. We investigated the impact of PRS integration method, as well as choices regarding training sample, model complexity, and performance metrics. Overall, our results show that including PRS resulted in higher performance by some metrics but the gain in performance was only robust when combined with demographic data alone. Improvements were inconsistent or negligible after including additional clinical information. The impact of genetic information on performance also varied by PRS integration method, with a small improvement in some cases from combining PRS with the output of a clinical model (late-fusion) compared to its inclusion an additional feature (early-fusion). The effects of other modeling decisions varied between institutions though performance increased with more compute-intensive models such as random forest. This work highlights the importance of considering methodological decision points in interpreting the impact on prediction performance when including PRS information in clinical models.
This study investigated the premarital contraceptive behavior of 222 male and female college students. Contraceptive practice was examined in relation to dating patterns, level of emotional involvement with the sex partner was heightened, the intercourse was planned, and the individual and prior sexual experience.
For the past five years, two required courses in research methodology have been presented to physical therapy students during their senior year. The overall objective was to prepare students to use the scientific method in their approach to physical therapy practice. The content of the first course included didactic instruction on the research process with emphasis on reading and interpreting the medical and scientific literature. In conjunction with this experience, students developed research proposals. During the second course, students gathered data, analyzed and synthesized results, and prepared a complete research paper. To date 67 projects have been completed. Reactions to this learning experience and samples of abstracts written by students are presented.
The present paper reports on the results of a complex epidemiologic survey of the epidemiologic potential of influenza in Bucharest in 1974, conducted on the basis of a complete, unitary methodology including; (a) Dynamic survey of the morbidity and mortality from influenza, with statistical-mathematical processing of the data per age group and total population; (b) Monthly sero-epidemiologic survey of the antiinfluenza immunologic profile of the population, determined in lots of 540 sera (annual total 7020 serum samples), with statistical-mathematical processing of the serograms; (c) Serodynamic determinations of 67 paired serum smaples collected from patients presenting influenza syndromes during ascension of the epidemic morbidity from influenza; (d) Complex epidemiologic surveys in representative influenza foci in children, adolescent and adult communities. Based upon the result obtained the authors discuss the evolutive particularities of the epidemiologic process in Bucharest, particularly during the epidemic ascension of the first trimester of 1974, caused by the intensified circulation of influenza virus type B. The orientative value of certain elements for the epidemiologic prognosis is emphasized, such as: the immunologic profile of the population per age group with regard to the circulating influenza virus strains (autochtonous or imported strains), active control of the incidence of influenza in communities (technical schools etc.) or enterprises with a large number of employees, laboratory etiologic determinations in cases of a clinical diagnosis of influenza in a preepidemic season. The authors' ten years experience in the active survey of the active epidemiologic potential of influenza in the town of Bucharest shows that the methodology applied was efficient both for scientific assessing of the epidemiologic situation and for an orientation in the choice of preventive and control measures.