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Peripheral nervous system (PNS) injuries are an ongoing health care concern. While autografts and allografts are regarded as the current clinical standard for traumatic injury, there are inherent limitations that suggest alternative remedies should be considered for therapeutic purposes. In recent years, nerve guidance conduits (NGCs) have become increasingly popular as surgical repair devices, with a multitude of various natural and synthetic biomaterials offering potential to enhance the design of conduits or supplant existing technologies entirely. From a cellular perspective, it has become increasingly evident that Schwann cells (SCs), the primary glia of the PNS, are a predominant factor mediating nerve regeneration. Thus, the development of severe nerve trauma therapies requires a deep understanding of how SCs interact with their environment, and how SC microenvironmental cues may be engineered to enhance regeneration. Here we review the most recent advancements in biomaterials development and cell stimulation strategies, with a specific focus on how the microenvironment influences the behavior of SCs and can potentially lead to functional repair. We focus on microenvironmental cues that modulate SC morphology, proliferation, migration, and differentiation to alternative phenotypes. Promotion of regenerative phenotypic responses in SCs and other non-neuronal cells that can augment the regenerative capacity of multiple biomaterials is considered along with innovations and technologies for traumatic injury., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 The Authors. Published by Elsevier GmbH.. All rights reserved.)

Abstract: Traditional food markets frequently have inadequate infrastructure, limited access to potable water, unsanitary conditions, and inadequate storage facilities, making them especially risky places for the growth and spread of foodborne pathogens. Traditional markets also often lack effective government oversight. Government programs are important for providing a foundation to manage food safety by setting and enforcing minimum food safety and quality standards and by establishing uniform standards for the conduct of food businesses. Four regional guidelines developed by the Codex Alimentarius to improve the safety of street-vended food were examined for their application to traditional food markets. These guidelines provide important standards that can be used to improve food safety in traditional food markets in many countries, including advice to governments and market authorities in the areas of policy and regulation, infrastructure, food handling, vendor health and hygiene, and training and education. The guidelines can be supplemented with additional material from the World Health Organization and the Food and Agriculture Organization of the United Nations. However, given the gaps identified in the individual regional guidelines, a uniform international standard is needed for national, regional, and local governments to use when managing food safety in traditional markets., (Published 2022 by the International Association for Food Protection.)

Background: Benzodiazepines are the gold standard for alcohol withdrawal treatment but choice and dosing vary widely. In 2015, our institution implemented a Minnesota detoxification scale (MINDS) and single standardized high-dose diazepam based protocol for treatment of alcohol withdrawal to replace multiple Clinical Institute Withdrawal Assessment for Alcohol (CIWA) based protocols using lower dose benzodiazepines. We compared use of MINDS versus CIWA assessment protocols with high front loading diazepam treatment in care of patient experiencing alcohol withdrawal during hospitalization., Methods: Retrospective cohort study of hospitalized patients experiencing alcohol withdrawal to statistically analyze difference in outcomes between CIWA based lower benzodiazepine dose protocols used in 2013-2015 versus the MINDS based high-dose front-loading diazepam protocol used in 2015-2017., Results: Patients treated with MINDS based high dose diazepam protocol were less likely to have physical restraints used (AOR = 0.8, CI: 0.70-0.92), had a shorter hospital length of stay, and fewer days on benzodiazepines (p < 0.001). Patients were more likely to be readmitted to the hospital within 30 days (AOR = 1.13, CI: 1.03-1.26) in MINDS based diazepam treatment group. Total diazepam equivalent dosing was similar in both groups. Mortality rates and ICU use rates were similar between the groups., Conclusions: Higher dose front loading long acting benzodiazepine can be safely used with beneficial outcomes in hospitalized alcohol withdrawal patients., Competing Interests: Declaration of Competing Interest None., (Copyright © 2021 Southern Society for Clinical Investigation. Published by Elsevier Inc. All rights reserved.)

Background and Aim: Patients undergoing percutaneous coronary intervention (PCI) are at high-risk for hospital readmission. We examined the rate, factors associated with, and outcomes of 30-day readmissions for patients who underwent a PCI., Methods: We reviewed medical records of all patients who underwent PCI between 2011 and 2014 at a central New England radial first, tertiary care center. Data was collected on occurrence and cause of readmission as well as patients' bleeding events and survival at one year. Logistic regression was used to examine factors associated with 30-day readmission as well as its association with bleeding and all-cause mortality., Results: A total of 3858 patients were studied (mean age = 62.8 years with 26.1% women), among whom 348 (9.5%) patients were readmitted within 30-days. Cardiac causes of readmission represented 62% of all readmissions. In the multi-variable adjusted regression model, factors that were significantly associated with 30-day readmission included female gender, prior coronary bypass surgery, acute coronary syndrome, anemia, length of stay, and delay in initial presentation. Patients who were readmitted had more than twice the risk of bleeding and mortality at one year as compared to those who were not readmitted within 30 days., Conclusions: In conclusion, our results suggest that early hospital readmission after undergoing PCI is common and has not changed in recent years. Efforts should be made to identify and closely monitor patients who are at risk for readmission after PCI., Competing Interests: Declaration of competing interest The authors have no conflicts of interest to declare., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Background: Newly educated RNs are vulnerable to needle stick injuries (NSIs). Most needle stick injuries occur during practice and associated with nurses' practice and available resources., Methods: This was a quantitative, descriptive study. Registered nurses (N = 120) with less than three years' experience. Data collected using a 26-item questionnaire among newly registered nurses. Data were analyzed descriptively and inferentially using (SPSS) version 20., Results: Most of the nurses between the ages 20-30 years (49.7%), were female (73.4%), had 2 to <3 years' experience (44.2%) and experienced a needle stick injury (43.3%). Respondents knew about the policies on standard precautions but their practice was not compliant with safe practices. Adherence was associated with knowledge of policies on standard precautions (r. = 534, p < .01), having updated policies (r = .404, p < .01) and the appropriate use of resources (r. = 805, p < .01)., Conclusion: There are a number of factors that contribute to NSIs among newly registered nurses which are personal as well as structural. Avoidable practices such as non-adherence to standard precautions while using hypodermic needles contributed to NSIs. Mandatory training and evaluation of nurses' knowledge and attitude regarding safety practices should be examined., (Copyright © 2020 Australasian College for Infection Prevention and Control. Published by Elsevier B.V. All rights reserved.)

Background: In low malaria-endemic settings, screening and treatment of individuals in close proximity to index cases, also known as reactive case detection (RACD), is practised for surveillance and response. However, other approaches could be more effective for reducing transmission. We aimed to evaluate the effectiveness of reactive focal mass drug administration (rfMDA) and reactive focal vector control (RAVC) in the low malaria-endemic setting of Zambezi (Namibia)., Methods: We did a cluster-randomised controlled, open-label trial using a two-by-two factorial design of 56 enumeration area clusters in the low malaria-endemic setting of Zambezi (Namibia). We randomly assigned these clusters using restricted randomisation to four groups: RACD only, rfMDA only, RAVC plus RACD, or rfMDA plus RAVC. RACD involved rapid diagnostic testing and treatment with artemether-lumefantrine and single-dose primaquine, rfMDA involved presumptive treatment with artemether-lumefantrine, and RAVC involved indoor residual spraying with pirimiphos-methyl. Interventions were administered within 500 m of index cases. To evaluate the effectiveness of interventions targeting the parasite reservoir in humans (rfMDA vs RACD), in mosquitoes (RAVC vs no RAVC), and in both humans and mosquitoes (rfMDA plus RAVC vs RACD only), an intention-to-treat analysis was done. For each of the three comparisons, the primary outcome was the cumulative incidence of locally acquired malaria cases. This trial is registered with ClinicalTrials.gov, number NCT02610400., Findings: Between Jan 1, 2017, and Dec 31, 2017, 55 enumeration area clusters had 1118 eligible index cases that led to 342 interventions covering 8948 individuals. The cumulative incidence of locally acquired malaria was 30·8 per 1000 person-years (95% CI 12·8-48·7) in the clusters that received rfMDA versus 38·3 per 1000 person-years (23·0-53·6) in the clusters that received RACD; 30·2 per 1000 person-years (15·0-45·5) in the clusters that received RAVC versus 38·9 per 1000 person-years (20·7-57·1) in the clusters that did not receive RAVC; and 25·0 per 1000 person-years (5·2-44·7) in the clusters that received rfMDA plus RAVC versus 41·4 per 1000 person-years (21·5-61·2) in the clusters that received RACD only. After adjusting for imbalances in baseline and implementation factors, the incidence of malaria was lower in clusters receiving rfMDA than in those receiving RACD (adjusted incidence rate ratio 0·52 [95% CI 0·16-0·88], p=0·009), lower in clusters receiving RAVC than in those that did not (0·48 [0·16-0·80], p=0·002), and lower in clusters that received rfMDA plus RAVC than in those receiving RACD only (0·26 [0·10-0·68], p=0·006). No serious adverse events were reported., Interpretation: In a low malaria-endemic setting, rfMDA and RAVC, implemented alone and in combination, reduced malaria transmission and should be considered as alternatives to RACD for elimination of malaria., Funding: Novartis Foundation, Bill & Melinda Gates Foundation, and Horchow Family Fund., (Copyright © 2020 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license. Published by Elsevier Ltd.. All rights reserved.)

Only a few studies concerning Shiga toxin-producing E. coli (STEC) detection in bivalves and their harvesting areas have been reported, and to the best of our knowledge there are no outbreaks associated with STEC from bivalves described. The aim of the present study was to investigate the occurrence of STEC in Norwegian bivalves, and to characterize potential STEC isolated from the samples. A total of 269 samples of bivalves were screened for the presence of stx and eae genes, and markers for the serogroups O26, O103, O111, O145 and O157 by using ISO TS 13136 (2012). The screening returned 19 samples that were positive for stx and eae, and attempts of isolation of STEC were made from these samples. Presumptive STEC were obtained from three samples, and three isolates (one from each sample) were subjected to whole-genome-sequencing (WGS). The WGS revealed that one of the isolates did not carry the stx genes, while the other two were identified as stx 2i positive E. coli O9:H19 and stx 2g positive E. coli O96:H19. Neither of the two STEC isolates were positive for virulence markers such as eae and ehx. The results suggest that the occurrence of STEC in Norwegian bivalves is low., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Introduction: Residents learn technical and communication skills during training and practice both concurrently during awake surgical procedures. Patients have expressed mixed views on resident involvement in their surgical care, making this context challenging for residents to navigate. We sought to qualitatively explore resident perspectives on teaching during awake surgical procedures., Methods: Residents in Urology, Obstetrics and Gynecology, and General Surgery who had been exposed to 10 or more awake surgical procedures were recruited for recorded focus groups at the University of Chicago. Recordings were transcribed, coded, and reviewed by 3 researchers using the constant comparative method until thematic saturation was reached., Results: Twenty-five residents participated in 5 focus groups. Residents identified positive educational techniques during awake surgery including preprocedural communication, explaining teaching and the resident role, whispering/nonverbal communication, involving the patient in education, and confident educator. Residents described challenges and failures in education, including hesitating to ask questions, hesitating to correct a learner, whispering/nonverbal communication, and taking over. In discussing informed consent during awake procedures, some residents described that the consent process should or did change during awake procedures, for example, to include more information about the resident role., Conclusions: Residents participating in awake surgical procedures offer new insights on successful techniques for teaching during awake surgery, emphasizing that good communication in the procedure room starts beforehand. They also identify challenges with teaching in this context, often related to a lack of open and clear communication., (Copyright © 2019 Association of Program Directors in Surgery. Published by Elsevier Inc. All rights reserved.)

Objective: The spillover hypothesis suggests that childhood aggression results from spillover of interparental conflict to poor parenting, which promotes aggressive child behavior. This study was designed to examine the spillover hypothesis in non-genetically related parent-child dyads from the toddler period through age 6 years., Method: A sample of 361 sets of children, adoptive parents, and birth parents from the Early Growth and Development Study (EGDS) was assessed from child age 9 months to 6 years on measures of adoptive parent financial strain, antisocial traits, marital hostility, hostile parenting, and child aggression. Structural equation modeling was used to examine links from financial strain, parent antisocial traits, and marital hostility in infancy and toddlerhood to hostile parenting and child aggression at ages 4.5 and 6 years., Results: Spillover of marital conflict from child age 18 to 27 months was associated with more parental hostility in mothers and fathers at 27 months. In turn, adoptive fathers' parental hostility, but not mothers', was associated with aggression in children at age 4.5 years. However, there was no significant spillover from hostile parenting at 4.5 years to child aggression at 6 years. Birth mother antisocial traits were unassociated with child aggression., Conclusion: This study is the first to examine spillover of marital hostility to parenting to child aggression from toddlerhood through age 6 years in an adoption design, highlighting the impact of these environmental factors from the toddler to preschool period. The findings support the potential benefit of early identification of marital hostility., (Copyright © 2016 American Academy of Child and Adolescent Psychiatry. Published by Elsevier Inc. All rights reserved.)

Microbes play an important role in the degradation of fish products, thus better knowledge of the microbiological conditions throughout the fish production chain may help to optimise product quality and resource utilisation. This paper presents the results of a ten-year spot sampling programme (2005-2014) of the commercially most important pelagic fish species harvested in Norway. Fish-, surface-, and storage water samples were collected from fishing vessels and processing factories. Totally 1,181 samples were assessed with respect to microbiological quality, hygiene and food safety. We introduce a quality and safety assessment scheme for fresh pelagic fish recommending limits for heterotrophic plate counts (HPC), thermos tolerant coliforms, enterococci and Listeria monocytogenes. According to the scheme, in 25 of 41 samplings, sub-optimal conditions were found with respect to quality, whereas in 21 and 9 samplings, samples were not in compliance concerning hygiene and food safety, respectively. The present study has revealed that the quality of pelagic fish can be optimised by improving the hygiene conditions at some critical points at an early phase of the production chain. Thus, the proposed assessment scheme may provide a useful tool for the industry to optimise quality and maintain consumer safety of pelagic fishery products., (Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.)

In mice the transcription factor Elf5 is necessary for correct trophoblast development. Upon knockdown of Elf5, TS cells display neither a decrease in proliferation nor an increase in cell death but rather an increased propensity to differentiate. Such cells rapidly lose Sox2 and 3 expression, while transiently upregulating the giant cell differentiation determinant gene Hand1. Other genes affected within 24h of Elf5 knock-down, many of which have not previously been implicated in trophoblast development, exhibited in vivo expression domains and in vitro expression responses consistent with Elf5 having a role in counteracting trophoblast differentiation. In an ES to TS differentiation assay using Cdx2 overexpression with Elf5 loss of function cell lines, it was shown that Elf5 is necessary to prevent terminal trophoblast differentiation. This data thus suggest that Elf5 is a gatekeeper for the TS to differentiated trophoblast transition thereby preventing the precocious differentiation of the undifferentiated extraembryonic ectoderm., (Copyright © 2014 Elsevier Inc. All rights reserved.)

The very nature of the Patient-Centered Medical Home (PCMH) necessitates new instructional models that prepare learners for the roles they will have to assume in these transformed primary care practices. In this manuscript we describe a new instructional framework that seeks to blend the goals of patient-centered care and inter-professional education, and can be implemented in existing training environments while practice transformation continues to proceed. We propose a 5-step process, the EFECT framework, which is simultaneously a sequence of tasks for effective patient care and a guide for the learners and faculty in teaching and evaluating that care delivery. These steps include: (1) Eliciting a patient-centered narrative, (2) Facilitating an inter-professional team discussion, (3) Evaluating clinical evidence, (4) Creating a shared care plan, and (5) Tracking outcomes. We then report preliminary descriptive outcomes from the first EFECT pilot. Our proposed framework supports learners' abilities to construct a patient-centered narrative from multiple professional perspectives as the basis for developing an evidence-based, integrated care plan between the patient and the inter-professional care team and deliberately following up on outcomes. We present this framework to stimulate a process for creating new curricula and evaluative tools to measure and promote learner functioning in medical home environments., (Copyright © 2013. Published by Elsevier Inc.)

Malaria-eliminating countries achieved remarkable success in reducing their malaria burdens between 2000 and 2010. As a result, the epidemiology of malaria in these settings has become more complex. Malaria is increasingly imported, caused by Plasmodium vivax in settings outside sub-Saharan Africa, and clustered in small geographical areas or clustered demographically into subpopulations, which are often predominantly adult men, with shared social, behavioural, and geographical risk characteristics. The shift in the populations most at risk of malaria raises important questions for malaria-eliminating countries, since traditional control interventions are likely to be less effective. Approaches to elimination need to be aligned with these changes through the development and adoption of novel strategies and methods. Knowledge of the changing epidemiological trends of malaria in the eliminating countries will ensure improved targeting of interventions to continue to shrink the malaria map., (Copyright © 2013 Elsevier Ltd. All rights reserved.)

Background: Efforts to reduce door-to-balloon (DTB) times for patients presenting with an ST-elevation myocardial infarction (STEMI) are widespread. Reductions in DTB times have been shown to reduce short-term mortality and decrease inpatient length of stay (LOS) in these high-risk patients. However, there is a limited literature examining the effect that these quality improvement (QI) initiatives have on patient care costs., Methods: A STEMI QI program (Cardiac Alert Team [CAT]) initiative was instituted in July 2006 at a single tertiary care medical center located in central Massachusetts. Information was collected on cost data and selected clinical outcomes for consecutively admitted patients with a STEMI. Differences in adjusted hospital costs were compared in three cohorts of patients hospitalized with a STEMI: one before the CAT initiative began (January 2005-June 2006) and two after (October 1, 2007-September 30, 2009, and October 1, 2009-September 30, 2011)., Results: Before the CAT initiative, the average direct inpatient costs related to the care of these patients was $14,634, which decreased to $13,308 (-9.1%) and $13,567 (-7.3%) in the two sequential periods of the study after the CAT initiative was well established. Mean DTB times were 91 minutes before the CAT initiative and were reduced to 55 and 61 minutes in the follow-up periods (p < .001). There was a nonsignificant reduction in LOS from 4.4 days pre-CAT to 3.6 days in both of the post-CAT periods (p = .11)., Conclusions: A QI program aimed at reducing DTB times for patients with a STEMI also led to a significant reduction in inpatient care costs. The greatest reduction in costs was related to cardiac catheterization, which was not expected and was likely a result of standardization of care and identification of practice inefficiencies.

Background: We evaluated the utility of an independent biomarker of early ischemic cellular damage-circulating fractional forms of C-reactive protein (fracCRP), to verify the diagnostic relevance of low Troponin I (TnI) values within the context of a workup for Acute Coronary Syndrome (ACS)., Methods: On a semi-preparative scale, the molecular characteristics of fracCRP were established by electron microscopy and Western Blot, using isolates captured from patient serum on phosphorylcholine beads and purified by size exclusion high-pressure liquid chromatography (SE-HPLC). Captured on an analytical scale, the diagnostic utility of fracCRP was evaluated in first-draw plasma specimens (total CRP not exceeding 6 mg/l) recovered from 300 cardiac emergency patients with final discharge diagnoses of ACS ruled out (N=132) or ruled in (N=168)., Results: At a cutoff value chosen for 97.7% test specificity, the test metric (fracCRP×TnI) identified in the first blood draw 39.9% of all emergency patients ultimately diagnosed with ACS, and 17.9% of ultimately diagnosed patients who arrived with TnI values within the normal reference range (0.01-0.04 ng/ml)., Conclusions: These findings suggest that the fracCRP test metric could serve as a rule-in test for ACS in a significant proportion of low to moderate risk emergency patients., (Copyright © 2012 Elsevier B.V. All rights reserved.)

In the National Toxicology Program's toxicity studies, rats were more sensitive than mice to Bis(2-chloroethoxy)methane (CEM) - induced cardiac toxicity following dermal application to male and female F344/N rats and B6C3F1 mice. Thiodiglycolic acid (TDGA) is a major metabolite of CEM in rats. It has been implicated that chemicals metabolized to TDGA cause cardiac toxicity in humans. Therefore, the toxicokinetics of CEM and TDGA were investigated in male and female F344/N rats and B6C3F1 mice following a single intravenous administration or dermal application of CEM to aid in the interpretation of the toxicity data. Absorption of CEM following dermal application was rapid in both species and genders. Bioavailability following dermal application was low but was higher in rats than in mice with females of both species showing higher bioavailability than males. CEM was rapidly distributed to the heart, thymus, and liver following both routes of administration. Plasma CEM C(max) and AUC(∞) increased proportionally with dose, although at the dermal dose of 400mg/kg in rats and 600mg/kg in mice non-linear kinetics were apparent. Following dermal application, dose-normalized plasma CEM C(max) and AUC(∞) was significantly higher in rats than in mice (p-value<0.0001 for all comparisons except for C(max) in the highest dose groups where p-value=0.053). In rats, dose-normalized plasma CEM C(max) and AUC(∞) was higher in females than in males: however, the difference was significant only at the lowest dose (p-value=0.009 for C(max) and 0.056 for AUC(∞)). Similar to rats, female mice also showed higher C(max) and AUC(∞) in females than in male: the difference was significant only for C(max) at the lowest dose (p-value=0.002). Dose-normalized heart CEM C(max) was higher in rats than in mice and in females than their male counterparts. The liver CEM C(max) was lower compared to that of heart and thymus in both rats and mice following intravenous administration and in rats following dermal application. This is likely due to the rapid metabolism of CEM in the liver as evidenced by the high concentration of TDGA measured in the liver. Dose-normalized plasma and heart TDGA C(max) values were higher in rats compared to mice. In rats, females had higher plasma and heart TDGA C(max) than males; however, there was no gender difference in plasma or heart TDGA C(max) in mice. These findings support the increased sensitivity of rats compared to mice to CEM-induced cardiac toxicity. Data also suggest that, either CEM C(max) or AUC can be used to predict the CEM-induced cardiac toxicity. Although, both plasma and heart TDGA C(max) was consistent with the observed species difference and the gender difference in rats, the gender difference in mice to cardiac toxicity could not be explained based on the TDGA data. This animal study suggests that toxicologically significant concentrations of CEM and TDGA could possibly be achieved in the systemic circulation and/or target tissues in humans as a result of dermal exposure to CEM., (Published by Elsevier Ireland Ltd.)

The recent influenza pandemic, caused by a novel H1N1 influenza A virus, as well as the seasonal influenza outbreaks caused by varieties of influenza A and B viruses, are responsible for hundreds of thousands of deaths worldwide. Few studies have evaluated the utility of real-time reverse transcription-PCR to detect influenza virus RNA from formalin-fixed, paraffin-embedded tissues obtained at autopsy. In this work, respiratory autopsy tissues from 442 suspect influenza cases were tested by real-time reverse transcription-PCR for seasonal influenza A and B and 2009 pandemic influenza A (H1N1) viruses and the results were compared to those obtained by immunohistochemistry. In total, 222 cases were positive by real-time reverse transcription-PCR, and of 218 real-time, reverse transcription-PCR-positive cases also tested by immunohistochemistry, only 107 were positive. Although formalin-fixed, paraffin-embedded tissues can be used for diagnosis, frozen tissues offer the best chance to make a postmortem diagnosis of influenza because these tissues possess nucleic acids that are less degraded and, as a consequence, provide longer sequence information than that obtained from fixed tissues. We also determined that testing of all available respiratory tissues is critical for optimal detection of influenza virus in postmortem tissues., (Copyright © 2011 American Society for Investigative Pathology and the Association for Molecular Pathology. Published by Elsevier Inc. All rights reserved.)

The efficacy of a therapeutic IgG molecule may be as dependent on the optimisation of the constant region to suit its intended indication as on the selection of its variable regions. A crucial effector function to be maximised or minimised is antibody-dependent cell-mediated cytotoxicity by natural killer cells. Traditional assays of ADCC activity suffer from considerable inter-donor and intra-donor variability, which makes the measurement of antibody binding to human FcgammaRIIIa, the key receptor for ADCC, an attractive alternative method of assessment. Here, we describe the development of cell lines and assays for this purpose. The transmembrane receptor, FcgammaRIIIa, requires co-expression with signal transducing subunits to prevent its degradation, unlike the homologous receptor FcgammaRIIIb that is expressed as a GPI-anchored molecule. Therefore, to simplify the production of cell lines as reliable assay components, we expressed FcgammaRIIIa as a GPI-anchored molecule. Separate, stable CHO cell lines that express either the 158F or the higher-affinity 158V allotype of FcgammaRIIIa were isolated using fluorescence-activated cell sorting. The identities of the expressed receptors were confirmed using a panel of monoclonal antibodies that distinguish between subclasses and allotypes of FcgammaRIII and the cell lines were shown to have slightly higher levels of receptor than FcgammaRIII-positive peripheral blood mononuclear cells. Because the affinity of FcgammaRIIIa for IgG is intermediate amongst the receptors that bind IgG, we were able to use these cell lines to develop flow cytometric assays to measure the binding of both complexed and monomeric immunoglobulin. Thus, by choosing the appropriate method, weakly- or strongly-binding IgG can be efficiently compared. We have quantified the difference in the binding of wildtype IgG1 and IgG3 molecules to the two functional allotypes of the receptor and report that the FcgammaRIIIa-158V-antibody interaction is 3- to 4-fold stronger that the interaction with FcgammaRIIIa-158F. Overall, these robust assays should be valuable for batch-testing clinical material as well as providing tools for improving the design of therapeutic IgG., (2010 Elsevier B.V. All rights reserved.)

We conducted an interlaboratory study which differed from the typical study of this type because of its emphasis on comparing intralaboratory variability in results. We sent specimens to six laboratories experienced in the analysis of perfluorinated alkyl compounds in blood matrices and that use stringent procedures to control and assure accuracy and precision. Each received an identical set of 60 plasma specimens that were analyzed in six completely independent batches. Split specimens were included so that within- and between-batch coefficients of variation could be calculated. All laboratories used liquid chromatography-tandem mass spectrometry (LC-MS/MS). The concentrations of perfluorooctanesulfonate (PFOS), perfluorooctanoate (PFOA), and perfluorohexanesulfonate (PFHxS) measured in the specimens in general showed a high level of agreement, although in some cases the agreement was only moderate. The average within- and between-batch coefficient of variation for PFOS was 9.1% and 9.3%; for PFOA was 14.5% and 14.5%; and for PFHxS was 14.5% and 17.0%. The recent availability of labeled internal standards, among other advances, has facilitated improvement in the accuracy and precision of the assays. Considering the degree of between-subject variation in levels among people in background-exposed populations, the results indicate that biomarker-based epidemiologic studies of associations with health could have reasonable precision.

Objective: To determine the accuracy of reporting of self-monitored blood glucose in pregnant women with diabetes., Design: A descriptive study. Patient-recorded logs of self-monitored blood glucose values were compared to meter memory values., Setting and Participants: A convenience sample of 85 pregnant women with pregestational and gestational diabetes enrolled in a perinatal diabetes program in an urban teaching hospital., Results: Accuracy significantly differed by diabetes type (p = .015). Women with type 1 diabetes did not accurately record on average 36.7% of blood glucose values as compared to 8.5% of type 2, 21.2% of GDMA(1) (gestational diabetes mellitus, diet controlled), and 23.4% of GDMA(2) (gestational diabetes mellitus, insulin controlled). Age positively affected accuracy, but accuracy was not affected by marital status, educational background, or duration of diabetes. Statistical significance was shown between values from women with private health insurance and women with Medicaid. Eighty percent of the sample overreported by adding phantom values in the logbook, which did not differ by diabetes type. Approximately 70% underreported by not logging values in the meter memory that was statistically significant by diabetes type., Conclusion: Assessment of the reliability of self-monitored blood glucose results from pregnant women with diabetes is recommended owing to a significant degree of falsification.

Like other bacteriophages, T7 has a singular vertex that is the site of a symmetry mismatch involving the portal/connector protein, a 12-fold ring at the vertex site which is also a 5-fold axis for the icosahedral capsid. In the mature virion, a 6-fold-symmetric tail extends outwards from the connector. T7 also has a cylindrical "core" that assembles on the inner surface of the connector during procapsid formation, is retained in the mature virion, and is required for infectivity. We have investigated the core structure by cryo-electron microscopy and image analysis of procapsids and find that it observes 8-fold symmetry. Stoichiometry data indicate that its major constituent is an octamer of gp15.

Computerized tomographic colonography (CT colonography) is a new, non-invasive technique that has been developed over the last few years; it looks at the large bowel in detail. In this chapter we look at how the examination is performed and we consider how the images are displayed. We describe the normal features of the colon, as seen using this technique, as well as the features of common pathological conditions. We will discuss screening for colorectal cancer and the performance of CT colonography; we compare the latter with other procedures currently employed in the screening and diagnosis of colorectal pathology. We consider the difficulties in interpreting these CT colonographic images and look at ways to overcome such difficulties. Finally we discuss future developments of this exciting, new technique., (Copyright 2002 Elsevier Science Ltd.)

Purpose: To survey the prevalence and severity of premenstrual symptoms and compare premenstrual symptom clusters of younger (13-15-year-old) and older (16-18-year-old) adolescents, based on both chronological and gynecological age., Methods: Physical, emotional, and behavioral premenstrual symptoms were assessed by self-report using the Premenstrual Assessment Form (PAF), in a sample of 75 adolescents. Analyses were performed to determine differences in premenstrual symptom clusters in younger and older adolescents., Results: The participants had a mean age of 14.8; 96% identified themselves as Caucasian, 3% as African-American, and 1% as Asian. All participants reported at least one premenstrual symptom of minimal severity. Many reported symptoms that they considered moderate (88%), severe (73%), or extreme (56%). The symptoms most commonly reported were food cravings, breast swelling, abdominal discomfort, mood swings, stressed feeling, and dissatisfaction with appearance. Other symptoms, such as missing time at school, becoming violent with people or things, and "thinking of what it would be like to do something to self" (such as crash the car), wishing to go to sleep and not wake up, or having thoughts of death or suicide, were less frequently reported. The younger teens (13-15 years old) had significantly less intense symptoms than the older teens (16-18 years old)., Conclusions: Premenstrual symptoms reported as being moderate or greater in severity were found to be quite prevalent (88%) in this sample of adolescents. Specifically those adolescents at 41 months postmenarche or greater reported specifically more intense premenstrual symptoms. In addition, a subset of adolescents expressed that they experienced aberrant behavior and passive suicidal ideations as premenstrual symptoms.

The effects of cyclosporin A (CSP) on tumor necrosis factor-alpha (TNF-alpha) RNA levels and protein production in human B cells and a B cell line were studied. The ability of CSP to block induction of RNA was compared to its inhibition of protein production in response to anti-IgM, phorbol ester (PMA) and platelet-activating factor (PAF). PAF is a phospholipid which has recently been found to activate human B cells. CSP blocks PAF-induced TNF-alpha RNA from the Ramos cell line, as well as inhibiting the enhancement of TNF protein production from both freshly isolated and Ramos B cells. CSP also blocks anti-Ig induced TNF-alpha RNA and protein but does not inhibit PMA-induced TNF-alpha. We conclude that B cells, like T cells, have CSP-independent and CSP-dependent signaling pathways and that PAF signaling is dependent upon a CSP-sensitive factor.

Nuclear factor kappa B (NF-kappa B) has been shown to be an important transcriptional regulatory protein in multiple cell types in response to a number of physiological signals. In lymphocytes it has been implicated in transcriptional regulation of the kappa light chain, MHC, IL-6, and IL-2 receptor genes, depending on the differentiation state of the cell. In the present study we demonstrate that platelet-activating factor (PAF), a phospholipid molecule, activates NF-kappa B and increases kappa light chain mRNA in a human B cell line. Treatment of Ramos cells with PAF (10(-9) to 10(-6) M) increased RNA levels of the NF-kappa B p50 precursor, known as p105, in a dose-dependent manner. p105 RNA levels increased to a maximum observed at 8-10 hr and then diminished by 24 hr; this induction was not blocked by cycloheximide (CHX). PAF induced nuclear kappa B binding at similar concentrations, but more rapidly, attaining maximal levels within 15 min. CHX did not block this activity either. PAF treatment of Ramos cells also resulted in increased levels of RNA for kappa light chain. These results suggest that PAF activates NF-kappa B by at least two mechanisms in these cells, one at the level of post-translational protein activation and the other by increasing the level of RNA for NF-kappa B p105.

The development of a rapid high-performance liquid chromatographic method for the determination of amitriptyline, amitriptyline-N-oxide, 10-hydroxyamitriptyline, 10-hydroxynortriptyline (E and Z isomers), nortriptyline and desmethylnortriptyline in plasma and liver tissue is described. A liquid--liquid extraction with hexane--butanol and back-extraction into phosphoric acid provides efficient extraction of amitriptyline-N-oxide along with amitriptyline and the other metabolites. A Supelcosil C8 reversed-phase column with 5-micron packing and a methanol--sodium phosphate buffer--amine modifier mobile phase was used. The combination of mobile phase pH and amine modifier concentration for the best separation within a reasonable analysis time for all seven solutes plus an internal standard was determined using a factorial design coupled with a multi-factor window diagram technique. Ultraviolet detection at 214 nm provided limits of detection of approximately 1 ng/ml.

A rapid and reliable procedure, based on a C8 bonded phase extraction and reversed-phase isocratic high-performance liquid chromatographic separation with internal standard quantitation, has been developed for the determination of the antipsychotic drug chlorpromazine and thirteen common metabolites. The method allows quantitation of these analytes at the ng/ml concentration range in human plasma. An evaluation of recovery, detection limits, and reproducibility is presented along with application of the method to patient samples.