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Background: Pain after vaginal delivery may result from episiotomy, perineal laceration, or uterine involution. Many women have indwelling epidural catheters in place at delivery. We hypothesized that a small dose of epidural morphine would be an effective strategy for postpartum analgesia.Methods: Eighty-one healthy parturients receiving epidural analgesia for labor were enrolled. Patients were randomized in double-blind fashion to 1 of 3 groups: all groups received a 4-mL volume of epidural solution consisting of saline (group 1, control), 1 mg (group 2), or 2 mg morphine (group 3) after vaginal delivery. During the first 24 hours postpartum, patients were evaluated for the amount of oral pain medication requested; visual analog scale scores for pain at rest and with movement; satisfaction with postpartum pain treatment; and opioid side effects including nausea, pruritus, urinary retention, and respiratory depression.Results: Patients who received 2 mg of epidural morphine used an average of 0.7 (0-1, interquartile range) opioid-containing pain pills (acetaminophen with codeine or oxycodone) compared with 1.2 (0-2) in the 1-mg group and 1.9 (0-3) in the control group ( P = .07). There was a statistically significant difference in oral drug usage between those who received epidural morphine and those who did not ( P < .03). There were no differences in side effects except that at 12 hours postpartum there was an increase in Foley catheterization in the 1-mg morphine group ( P = .007).Conclusions: These results suggest that epidural morphine decreases the need for oral pain medication in the first 24 hours postpartum. No significant dose-dependent side effects were found. [ABSTRACT FROM AUTHOR]

We created a serious game to teach first year anesthesiology (CA-1) residents to perform general anesthesia for cesarean delivery. We aimed to investigate resident knowledge gains after playing the game and having received one of 2 modalities of debriefing. We report on the development and validation of scores from parallel test forms for criterion-referenced interpretations of resident knowledge. The test forms were intended for use as pre- and posttests for the experiment. Validation of instruments measuring the study's primary outcome was considered essential for adding rigor to the planned experiment, to be able to trust the study's results. Parallel, multiple-choice test forms development steps included: (1) assessment purpose and population specification; (2) content domain specification and writing/selection of items; (3) content validation by experts of paired items by topic and cognitive level; and (4) empirical validation of scores from the parallel test forms using Classical Test Theory (CTT) techniques. Field testing involved online administration of 52 shuffled items from both test forms to 24 CA-1's, 21 second-year anesthesiology (CA-2) residents, 2 fellows, 1 attending anesthesiologist, and 1 of unknown rank at 3 US institutions. Items from each form yielded near-normal score distributions, with similar medians, ranges, and standard deviations. Evaluations of CTT item difficulty (item p values) and discrimination (D) indices indicated that most items met assumptions of criterion-referenced test design, separating experienced from novice residents. Experienced residents performed better on overall domain scores than novices ( P  < .05). Kuder-Richardson Formula 20 (KR-20) reliability estimates of both test forms were above the acceptability cut of .70, and parallel forms reliability estimate was high at .86, indicating results were consistent with theoretical expectations. Total scores of parallel test forms demonstrated item-level validity, strong internal consistency and parallel forms reliability, suggesting sufficient robustness for knowledge outcomes assessments of CA-1 residents., Competing Interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© The Author(s) 2024.)

Background: Unprotected intercourse is common, especially among teens and young women. Access to intrauterine device (IUD) as emergency contraception (EC) can help interested patients more effectively prevent unintended pregnancy and can also offer ongoing contraception. This study evaluated young women's awareness of IUD as EC and interest in case of need., Study Design: We conducted a secondary analysis of data from young women aged 18-25 years, not desiring pregnancy within 12 months, and receiving contraceptive counseling within a cluster-randomized trial in 40 US Planned Parenthood health centers in 2011-2013 (n=1500). Heath centers were randomized to receive enhanced training on contraceptive counseling and IUD placement, or to provide standard care. The intervention did not focus specifically on IUD as EC. We assessed awareness of IUD as EC, desire to learn more about EC and most trusted source of information of EC among women in both intervention and control groups completing baseline and 3- or 6-month follow-up questionnaires (n=1138)., Results: At follow-up, very few young women overall (7.5%) visiting health centers had heard of IUD as EC. However, if they needed EC, most (68%) reported that they would want to learn about IUDs in addition to EC pills, especially those who would be very unhappy to become pregnant (adjusted odds ratio [aOR], 1.3; 95% confidence interval, 1.0-1.6, p<.05). Most (91%) reported a doctor or nurse as their most trusted source of EC information, over Internet (6%) or friends (2%), highlighting providers' essential role., Conclusion: Most young women at risk of unintended pregnancy are not aware of IUD as EC and look to their providers for trusted information. Contraceptive education should explicitly address IUD as EC., Implications: Few young women know that the IUD can be used for EC or about its effectiveness. However, if they needed EC, most reported that they would want to learn about IUDs in addition to EC pills, especially those very unhappy to become pregnant. Contraceptive education should explicitly address IUD as EC., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Background: Teaching trainees the knowledge and skills to perform general anesthesia (GA) for cesarean delivery (CD) requires innovative strategies, as they may never manage such cases in training. We used a multistage design process to create a criterion-referenced multiple-choice test as an assessment tool to evaluate CA1's knowledge related to this scenario., Methods: Three faculty created 33 questions, categorized as: (1) physiologic changes of pregnancy (PCP), (2) pharmacology (PHA), (3) anesthetic implications of pregnancy (AIP), and (4) crisis resource management principles (CRM). A Delphi process (3 rounds) provided content validation. In round 1, experts (n = 15) ranked questions on a 7-point Likert scale. Questions ranked ≥ 5 in importance by ≥ 70% of experts were retained. Five questions were eliminated, several were revised, and 1 added. In round 2, consensus (N = 14) was reached in all except 7 questions. In round 3 (N = 14), all questions stabilized. A pilot test of the 29-question instrument evaluating internal consistency, reliability, convergent validity, and item analysis was conducted with the July CA1 classes at our institution after a lecture on GA for CD (n = 26, "instructed group") and another institution with no lecture (n = 26, "uninstructed group"), CA2s (N = 17), and attendings (N = 10)., Results: Acceptable internal consistency and reliability was demonstrated (ρ = 0.67). Convergent validity coefficients between the CA1 uninstructed and instructed group suggested theoretical meaningfulness of the 4 sub-scales: PCP correlated at 0.29 with PHA, 0.35 with CRM, and 0.25 with AIP. PHA correlated with CRM and AIP at 0.23 and 0.28, respectively. The correlation between CRM and AIP was 0.29., Conclusion: The test produces moderately reliable scores to assess CA1s' knowledge related to GA for urgent CD.

Mentors rarely receive education about the unique needs of underrepresented scholars in the biomedical and behavioral sciences. We hypothesized that mentor-training and peer-mentoring interventions for these scholars would enrich the perceived quality and breadth of discussions between mentor-protégé dyads (i.e., mentor-protégé pairs). Our multicenter, randomized study of 150 underrepresented scholar-mentor dyads compared: 1) mentor training, 2) protégé peer mentoring, 3) combined mentor training and peer mentoring, and 4) a control condition (i.e., usual practice of mentoring). In this secondary analysis, the outcome variables were quality of dyad time and breadth of their discussions. Protégé participants were graduate students, fellows, and junior faculty in behavioral and biomedical research and healthcare. Dyads with mentor training were more likely than those without mentor training to have discussed teaching and work-life balance. Dyads with peer mentoring were more likely than those without peer mentoring to have discussed clinical care and career plans. The combined intervention dyads were more likely than controls to perceive that the quality of their time together was good/excellent. Our study supports the value of these mentoring interventions to enhance the breadth of dyad discussions and quality of time together, both important components of a good mentoring relationship., (© 2017 V. Lewis et al. CBE—Life Sciences Education © 2017 The American Society for Cell Biology. This article is distributed by The American Society for Cell Biology under license from the author(s). It is available to the public under an Attribution–Noncommercial–Share Alike 3.0 Unported Creative Commons License (http://creativecommons.org/licenses/by-nc-sa/3.0).)

Background: Current recommendations for women undergoing cesarean delivery include 15° left tilt for uterine displacement to prevent aortocaval compression, although this degree of tilt is practically never achieved. We hypothesized that under contemporary clinical practice, including a crystalloid coload and phenylephrine infusion targeted at maintaining baseline systolic blood pressure, there would be no effect of maternal position on neonatal acid base status in women undergoing elective cesarean delivery with spinal anesthesia., Methods: Healthy women undergoing elective cesarean delivery were randomized (nonblinded) to supine horizontal (supine, n = 50) or 15° left tilt of the surgical table (tilt, n = 50) after spinal anesthesia (hyperbaric bupivacaine 12 mg, fentanyl 15 μg, preservative-free morphine 150 μg). Lactated Ringer's 10 ml/kg and a phenylephrine infusion titrated to 100% baseline systolic blood pressure were initiated with intrathecal injection. The primary outcome was umbilical artery base excess., Results: There were no differences in umbilical artery base excess or pH between groups. The mean umbilical artery base excess (± SD) was -0.5 mM (± 1.6) in the supine group (n = 50) versus -0.6 mM (± 1.5) in the tilt group (n = 47) (P = 0.64). During 15 min after spinal anesthesia, mean phenylephrine requirement was greater (P = 0.002), and mean cardiac output was lower (P = 0.014) in the supine group., Conclusions: Maternal supine position during elective cesarean delivery with spinal anesthesia in healthy term women does not impair neonatal acid-base status compared to 15° left tilt, when maternal systolic blood pressure is maintained with a coload and phenylephrine infusion. These findings may not be generalized to emergency situations or nonreassuring fetal status.

Purpose: To conduct a randomized controlled trial to evaluate the effects of different mentoring interventions on the basic psychological need satisfaction of underrepresented minorities and women in academia., Method: Participants were 150 mentor/protégé dyads from three academic medical centers and eight other colleges and universities in western and central New York, randomized from 2010 to 2013 into mentor training (using principles of self-determination theory); peer mentoring for protégés; mentor training and peer mentoring for protégés combined; or control/usual practice. Protégé participants were graduate students, fellows, and junior faculty who were from underrepresented groups based on race, ethnicity, gender, or disability.The primary analysis was a comparison of intervention effects on changes in protégés' satisfaction of their basic psychological needs (competence, autonomy, and relatedness) with their mentor. They completed a well-validated, online questionnaire every two months for one year., Results: There was no significant effect at the end of one year of either mentor training or peer mentoring on protégés' psychological basic need satisfaction with mentor specifically or at work in general. Exploratory analyses showed a significant effect of the mentor-based intervention on the protégés' overall psychological need satisfaction with their mentor at two months, the time point closest to completing mentor training., Conclusions: This randomized controlled trial showed a potential short-term effect of mentor training on changing basic psychological need satisfaction of underrepresented scholars with their mentors. Despite the lack of sustained effect of either mentor training or peer mentoring, these short-term changes suggest feasibility and potential for future study.

In this review, we provide a description of those candidate biomarkers which have been demonstrated by multiple-omics approaches to vary in correlation with specific clinical manifestations of sickle cell severity. We believe that future clinical analyses of severity phenotype will require a multiomic analysis, or an omics stack approach, which includes integrated interactomics. It will also require the analysis of big data sets. These candidate biomarkers, whether they are individual or panels of functionally linked markers, will require future validation in large prospective and retrospective clinical studies. Once validated, the hope is that informative biomarkers will be used for the identification of individuals most likely to experience severe complications, and thereby be applied for the design of patient-specific therapeutic approaches and response to treatment. This would be the beginning of precision medicine for sickle cell disease., (© 2016 by the Society for Experimental Biology and Medicine.)

In this minireview, we cover the discovery of the human erythrocyte α spectrin E2/E3 ubiquitin conjugating/ligating enzymatic activity and the specific cysteines involved. We then discuss the consequences when this activity is partially inhibited in sickle cell disease and the possibility that the same attenuation is occurring in multiple organ dysfunction syndrome. We finish by discussing the reasons for believing that nonerythroid α spectrin isoforms (I and II) also have this activity and the importance of testing this hypothesis. If correct, this would suggest that the nonerythroid spectrin isoforms play a major role in protein ubiquitination in all cell types. This would open new fields in experimental biology focused on uncovering the impact that this enzymatic activity has upon protein-protein interactions, protein turnover, cellular signaling, and many other functions impacted by spectrin, including DNA repair., (© 2015 by the Society for Experimental Biology and Medicine.)

Zfra is a 31-amino-acid zinc finger-like protein, which participates in the tumor necrosis factor signaling. Here, we determined that when nude mice and BALB/c mice were pre-injected with nanogram levels of a synthetic Zfra1-31 or truncated Zfra4-10 peptide via tail veins, these mice became resistant to the growth, metastasis and stemness of melanoma cells, and many malignant cancer cells. The synthetic peptides underwent self-polymerization in phosphate-buffered saline. Alteration of the Ser8 phosphorylation site to Gly8 abolished Zfra aggregation and its-mediated cancer suppression in vivo. Injected Zfra peptide autofluoresced due to polymerization and was trapped mainly in the spleen. Transfer of Zfra-stimulated spleen cells to naïve mice conferred resistance to cancer growth. Zfra-binding cells, designated Hyal-2+ CD3- CD19- Z cells, are approximately 25-30% in the normal spleen, but are significantly downregulated (near 0-3%) in tumor-growing mice. Zfra prevented the loss of Z cells caused by tumors. In vitro stimulation or education of naïve spleen cells with Zfra allowed generation of activated Z cells to confer a memory anticancer response in naïve or cancer-growing mice. In particular, Z cells are abundant in nude and NOD-SCID mice, and can be readily activated by Zfra to mount against cancer growth.

In this minireview, we focus on advances in our knowledge of the human erythrocyte proteome and interactome that have occurred since our seminal review on the topic published in 2007. As will be explained, the number of unique proteins has grown from 751 in 2007 to 2289 as of today. We describe how proteomics and interactomics tools have been used to probe critical protein changes in disorders impacting the blood. The primary example used is the work done on sickle cell disease where biomarkers of severity have been identified, protein changes in the erythrocyte membranes identified, pharmacoproteomic impact of hydroxyurea studied and interactomics used to identify erythrocyte protein changes that are predicted to have the greatest impact on protein interaction networks.

The challenges of identifying and controlling emerging diseases impact individual health, as well as political, social and economic situations. In this review we discuss the role of proteomics for investigation of pathogen discovery, outbreak investigation, bio-defense, disease control, host-pathogen dynamics and vaccine development of emerging and neglected tropical diseases (NTDs). In the future the discipline of proteomics may help define multiple aspects of emerging and NTDs with respect to personalized medicine and public health.

The purpose of the present study was to investigate whether functional 20S and/or 26S proteasomes are present within mature human red blood cells (RBCs; depleted of reticulocytes and leukocytes). Double-immunofluorescence confocal microscopy showed the presence of immunoreactive 20S and 19S proteasomal subunit proteins and their partial co-localization within mature RBCs. Proteasomes isolated from mature RBCs displayed 20S activity in vitro; atomic-force and transmission electron microscopy of isolated proteasomes revealed abundant 20S core particles and very few 26S particles. A two-dimensional differential in-gel electrophoresis (2D-DIGE) approach was used to determine if proteasome-dependent protein degradation occurs within mature RBCs. Twenty-eight proteins were identified with altered protein content in response to lactacystin. Seven cytosolic proteins showed an increase and 16 showed a decrease; five membrane proteins showed a decrease. We conclude that the proteins showing increased abundance are either primary or secondary targets of the 20S proteasome and that putatively degraded proteins are secondary targets. Therefore, functional 20S proteasomes exist within mature RBCs. Our study did not detect 26S proteasome activity using the 2D-DIGE approach.

Mitochondrial structural and functional alterations appear to play to an important role in the pathogenesis of Alzheimer's disease (AD). In the present study, we used a quantitative comparative proteomic profiling approach to analyze changes in the mitochondrial proteome in AD. A triple transgenic mouse model of AD (3xTg-AD) which harbors mutations in three human transgenes, APP(Swe), PS1(M146V) and Tau(P301L), was used in these experiments. Quantitative differences in the mitochondrial proteome between the cerebral cortices of 6-month-old male 3xTg-AD and non-transgenic mice were determined by using two-dimensional difference gel electrophoresis (2D-DIGE) and tandem mass spectrometry. We identified 23 different proteins whose expression levels differed significantly between triple transgenic and non-transgenic mitochondria. Both down-regulated and up-regulated mitochondrial proteins were observed in transgenic AD cortices. Proteins which were dysregulated in 3xTg-AD cortices functioned in a wide variety of metabolic pathways, including the citric acid cycle, oxidative phosphorylation, pyruvate metabolism, glycolysis, oxidative stress, fatty acid oxidation, ketone body metabolism, ion transport, apoptosis, and mitochondrial protein synthesis. These alterations in the mitochondrial proteome of the cerebral cortices of triple transgenic AD mice occurred before the development of significant amyloid plaque and neurofibrillary tangles, indicating that mitochondrial dysregulation is an early event in AD., (Copyright © 2010 Elsevier B.V. All rights reserved.)

Hydroxyurea (HU) is an effective drug for the treatment of sickle cell disease (SCD). The main clinical benefit of HU is thought to derive from its capacity to increase fetal hemoglobin (HbF) production. However, other effects leading to clinical benefit, such as improved blood rheology, have been suggested. In order to understand HU-induced changes at the proteomic level, we profiled sickle RBC membranes from of HU-treated and untreated patients. Our previous in vitro profiling studies on sickle RBC membranes identified a significant increase in predominantly anti-oxidant enzymes, protein repair and degradation components and a few RBC cytoskeletal proteins. In the present study, using 2D-DIGE (Two-Dimensional Difference In-Gel Electrophoresis) and tandem mass spectrometry, we detected 32 different proteins that significantly changed in abundance in the HU treatment group. The proteins that significantly increased in abundance were mostly membrane skeletal components involved in the regulation of RBC shape and flexibility, and those showing a significant decrease were components of the protein repair and degradation machinery. RBC palmitoylated membrane protein 55 (p55) is significantly increased in abundance at low (in vitro) and high (in vivo) concentrations of HU. Palmitoylated p55 may be an important target of HU-dependent regulation of the sickle RBC membrane, consistent with our earlier in vitro studies., ((c) 2009 Elsevier B.V. All rights reserved.)

Protein interaction networks provide useful information to assess impacts of disease on cell functions. Statistical clustering methods applied to these networks can reveal impacts on particular functional groups of proteins. In addition, clustering methods can identify subsets of proteins that require additional study to provide updated information regarding their position within an interaction network, and hence increase our understanding of their relationships with other proteins in the network. These ideas are illustrated here by considering the impacts of sickle cell disease on the human erythrocyte interaction network. Statistical cluster analyses are performed based on a measure of similarity for nodes within a network called the Generalized Topological Overlap Measure. These analyses identify clusters of proteins that are similar in terms of shared interaction partners. Identification of clusters that contain proteins whose relative abundances have been significantly altered in sickle cell patients provides specific information about the impact of these proteins on erythrocyte functions.

Using two-dimensional difference gel electrophoresis (2D DIGE) we have analyzed monocytes derived from 10 sickle cell disease patients (5 males and 5 females ages 12-18) to generate hypotheses regarding signature proteins that appear most positively and negatively correlated with vasoocclusive event rate. Signature proteins have been identified by tandem mass spectrometry. Based on the limited number of samples analyzed, the most negatively correlated proteins related to crises rate were transketolase and coronin in the membrane fraction and heat shock 70 kDa protein cognate 4, and adenylate kinase isoenzyme 2, mitochondrial found in the cytosolic fraction. The protein spots that were most positively correlated with crisis rate in the cytoplasmic fraction were far upstream element-binding protein and Alpha actinin 1 or Alpha actinin 4. Utilizing StepSIM analysis, vinculin was able to classify all samples from the combined set and the membrane-only set, and cytosolic leukotriene A-4 hydrolase and phosphoglycerate kinase were also identified as important indicators for differentiating between low and high vasoocclusive event rates.

Background: There is controversy regarding the benefits and risks of combined spinal-epidural compared with epidural analgesia (CSE, EPID) for labor analgesia. We hypothesized that CSE would result in fewer patient requests for top-up doses compared to EPID., Methods: One-hundred ASA physical status I or II parous women at term in early labor (<5 cm cervical dilation) requesting analgesia were randomized in double-blind fashion to the EPID group (epidural bupivacaine 2.5 mg/mL, 3 mL, followed by bupivacaine 1.25 mg/mL, 10 mL with fentanyl 50 microg) or the CSE group (intrathecal bupivacaine 2.5 mg with fentanyl 25 microg). Both groups received identical infusions of bupivacaine 0.625 mg/mL with fentanyl 2 microg/mL at 12 mL/h. The primary outcome variable was the number of top-up doses requested to treat breakthrough pain., Results: There was no significant difference between the two groups in the percentage of patients requesting top-up doses (44% CSE vs 51% EPID; 95% confidence interval of the difference -28% to +14%) nor in the need for multiple top-up doses (14% CSE vs 15% EPID). Visual analog scale scores were lower in the CSE group compared to the EPID group at 10 min after initiation of analgesia [median 0 cm (0, 0) vs 4 cm (1, 6) respectively, P < 0.001] and at 30 min [0 cm (0, 0) vs 0 cm (0, 1), respectively, P = 0.03]., Conclusions: We did not find a difference in the need for top-up doses in parous patients; however, CSE provided better analgesia in the first 30 min compared to EPID.

Hydroxyurea (HU) is an effective oral drug for the management of homozygous sickle cell anemia (SS) in part because it increases fetal hemoglobin (HbF) levels within sickle red blood cells (RBCs) and thus reduces sickling. However, results from the Multicenter Study of HU suggested that clinical symptoms often improved before a significant increase in HbF levels occurred. This indicated that HU may be acting through the modification of additional cellular mechanisms that are yet to be identified. Hence, in this study, we focused on the analysis of the sickle RBC membrane proteome +/- HU treatment. 2D-DIGE (Two Dimensional Difference In-Gel Electrophoresis) technology and tandem mass spectrometry has been used to determine quantitative differences between sickle cell membrane proteins in the presence and absence of a clinically relevant concentration of HU. In vitro protein profiling of 13 sickle RBC membrane samples +/- 50 muM HU identified 10 statistically significant protein spots. Of these, the most remarkable class of proteins to show a statistically significant increase was the anti-oxidant enzymes-catalase, thioredoxin peroxidase and biliver-din reductase and the chaperonin containing TCP1 complex assisting in the folding of RBC cytoskeletal proteins. Interestingly, catalase immunoblots showed an increase in the acidic forms of the enzyme within sickle RBC membranes on incubation with 50 muM HU. We further identified this modification in catalase to be phosphorylation and demonstrated that HU exposed SS RBC membranes showed a 2-fold increase in tyrosine phosphorylation of catalase as compared to counterparts not exposed to HU. These results present an attractive model for HU-induced post-translational modification and potential activation of catalase in mature sickle RBCs. These findings also identify protein targets of HU other than fetal hemoglobin and enhance the understanding of the drug mechanism.

Administration of a low priming dose of 2-butoxyethanol (BE, 500 mg/kg, p.o.) 7 days prior to a larger LD(90) dose (1500 mg BE/kg, p.o.) offers protection against the lethal dose-induced hemolysis and death in female Sprague Dawley rats because of prompt and efficient replacement of red blood cells (RBCs) with new resilient RBCs. The objective of the present work was to analyze the altered proteome of RBCs upon priming with BE in order to identify the potential anti-hemolytic survival proteins induced in the primed rat RBCs (P-RBCs) as opposed to vehicle-treated RBCs (V-RBCs). The RBCs from the two groups were fractionated into membrane and cytosolic fractions. The cytosolic fractions were further fractionated for proteomic analysis into 3 fractions. The fractions were labeled with Cy3 and Cy5 fluorescent dyes and subjected to 2-dimensional differential gel electrophoresis (DIGE) to analyze the protein profiles. Seven membrane and 8 cytosolic proteins were found to be significantly increased (> or =2.5 fold) in P-RBCs as compared to V-RBCs. The identified proteins can be classified into antioxidant, membrane skeleton, protein turnover, lipid raft, and energy metabolism components. Increased levels of the proteins from antioxidant and membrane skeleton groups were confirmed by Western blot analysis. The study provides the first report on protein profiling of rat RBCs as well as on alteration of the proteome upon exposure to a priming dose of hemotoxicant. Further studies are needed to prove the protective role of the identified proteins and will initiate the field of survival/protective/anti-hemolytic proteins in RBCs.

We tested a hypothesis that force production by multi-finger groups leads to lower indices of force variability as compared to similar single-finger tasks. Three experiments were performed with quick force production, steady-state force production under visual feedback, and steady-state force production without visual feedback. In all experiments, a range of force levels was used computed as percentages of the maximal voluntary contraction force for each involved finger combination. Force standard deviation increased linearly with force magnitude across all three experiments and all finger combinations. There were modest differences between multi-finger and single-finger tasks in the indices of force variability, significant only in the tasks with steady-state force production under visual feedback. When fingers acted in groups, each finger showed significantly higher force variability as compared to its single-finger task and as compared to the multi-finger group as a whole. Fingers that were not instructed to produce force also showed close to linear relations between force standard deviation and force magnitude. For these fingers, indices of force variability were much higher as compared to those computed for the forces produced by instructed fingers. We interpret the findings within a feed-forward scheme of multi-finger control with two inputs only one of which is related to the explicit task. The total force variability reflects variability in only the task-related component, while variability of the finger forces is also due to variability of the component that is not related to the task. The findings tentatively suggest that total force variability originates at an upper level of the control hierarchy in accordance to the Weber-Fechner law rather than reflects a "neural noise" at the segmental level.

Studies involving two methods for measuring a continuous response are regularly conducted in health sciences to evaluate agreement of a method with itself and agreement between methods. Notwithstanding their wide usage, the design of such studies, in particular, the sample size determination, has not been addressed in the literature when the goal is the simultaneous evaluation of intra- and inter-method agreement. We fill this need by developing a simulation-based Bayesian methodology for determining sample sizes in a hierarchical model framework. Unlike a frequentist approach, it takes into account uncertainty in parameter estimates. This methodology can be used with any scalar measure of agreement available in the literature. We demonstrate this for four currently used measures. The proposed method is applied to an ongoing proteomics project, where we use pilot data to determine the number of individuals and the number of replications needed to evaluate the agreement between two methods for measuring protein ratios. We also apply our method to determine the sample size for an experiment involving measurement of blood pressure., ((c) 2007 John Wiley & Sons, Ltd.)

We depleted reticulocytes from erythrocytes of both sickle cell disease (SCD) subjects and healthy controls by four methods: fluorescence-activated cell sorting (FACS), Miltenyi immunomagnetic depletion (MACS), a combination of these methods (FACS + MACS) and Percoll density separation. The efficiency of these methods was assessed by new methylene blue staining and manual enumeration of the reticulocytes. FACS sorted erythrocytes from reticulocytes based on size and granularity, as well as the absence of dsDNA staining. MACS depleted reticulocytes from erythrocytes based on the immunoaffinity to CD36 and CD71. Reticulocytes from healthy controls were depleted to

The red blood cell or erythrocyte is easily purified, readily available, and has a relatively simple structure. Therefore, it has become a very well studied cell in terms of protein composition and function. RBC proteomic studies performed over the last five years, by several laboratories, have identified 751 proteins within the human erythrocyte. As RBCs contain few internal structures, the proteome will contain far fewer proteins than nucleated cells. In this minireview, we summarize the current knowledge of the RBC proteome, discuss alterations in this partial proteome in varied human disease states, and demonstrate how in silico studies of the RBC interactome can lead to considerable insight into disease diagnosis, severity, and drug or gene therapy response. To make these latter points we focus on what is known concerning changes in the RBC proteome in Sickle Cell Disease.