Intertriginous mycosis fungoides with T follicular helper cell phenotype progressing to Sézary syndrome.

This case report highlights the challenges in diagnosis and therapeutic options for an individual who initially presented with intertriginous mycosis fungoides with a T follicular helper cell phenotype, which later evolved to Sézary syndrome.

Association of maternal gestational weight gain with their offspring's anthropometric outcomes at late infancy and 6 years old: mediating roles of birth weight and breastfeeding duration.

BACKGROUND: Longitudinal studies examining the potential mediating roles of birth weight and breastfeeding duration on the pathways between maternal gestational weight gain (GWG) and offspring anthropometric outcomes are lacking. METHODS: We analyzed data from the mother-child pairs in the Infant Feeding Practices Study II (IFPS II) in late infancy (n=1548) and at the Year 6 Follow-up (n=1514) Study. Child anthropometrics included age- and sex-specific Z-scores for weight for age (WAZ), height /length for age, weight for height/length and body mass index (BMIZ). Structural equation models were used to estimate the total, direct and indirect effects of GWG on child anthropometrics through birth weight and breastfeeding duration. RESULTS: The total effect of GWG on offspring anthropometric outcomes was significant for WAZ (ß=0.107, 95% confidence interval (CI): 0.052, 0.161) at late infancy and for WAZ (ß=0.122, 95% CI: 0.066, 0.177) and BMIZ (ß=0.120, 95% CI: 0.063, 0.178) at 6 years old. The direct effects of GWG on offspring's WAZ and BMIZ were observed only at 6 years old. The indirect effects of GWG through birth weight were significant on most of the offspring's anthropometric measures. Compared to breastfeeding duration, birth weight was a stronger mediator on the pathways between GWG and all proposed anthropometric measures both in late infancy and in early childhood. Longer duration of breastfeeding was inversely associated with all offspring anthropometric outcomes at late infancy but not with those outcomes at 6 years old. CONCLUSIONS: Our findings suggest a stronger indirect rather than direct effect of GWG on children's anthropometric outcomes mainly through birth weight, independent of maternal sociodemographic and reproductive factors. Longer duration of breastfeeding might suppress the positive relationship between GWG, birth weight and anthropometric outcomes in late infancy but not among 6 years old.

Onychomadesis: literature review.

Onychomadesis is characterized by separation of the nail plate from the matrix with persistent attachment to the nail bed and often, but not always, eventual shedding. Onychomadesis has been associated with infection, autoimmune disease, critical illness and medications. To our knowledge a literature review of all associations with onychomadesis has not been completed previously. Most commonly, onychomadesis has been reported in association with pemphigus vulgaris and hand-foot-mouth disease, and following chemotherapy or antiepileptic medications. This article summarizes these key culprit associations, postulates the pathogenesis of nail matrix arrest and summarizes the clinical outcomes. We conducted a retrospective review of cases of onychomadesis reported from January 1960 to March 2013. Using the PubMed database, the literature was searched using the following terms: 'onychomadesis' and 'proximal nail shedding'. Also, an Ovid search was carried out using the same terms. In total 56 articles have been published, including our previously reported series of idiopathic onychomadesis. Articles pertaining only to Beau's lines and not true onychomadesis were excluded. Onychomadesis has been associated with autoimmune disease, other major medical illness, neonatal illness, medication and infection.

Use of state administrative data sources to study adolescents and young adults with rare conditions.

BACKGROUND: Effective care of young people with rare conditions requires ongoing coordinated medical treatment as well as educational and social support services. However, information on treatment is often lacking due to limited data. South Carolina has a repository of comprehensive health and human service data with which individuals may be tracked across the data systems of multiple state agencies and organizations. OBJECTIVE: To develop a method for studying health care of young persons with rare conditions using this repository. METHODS: We identified individuals aged 15 to 24 years diagnosed during 2000-2010 with Fragile X syndrome (FXS), spina bifida (SB), or muscular dystrophy (MD) using a series of algorithms. ICD-9-CM codes were used to initially identify the cohort from medical billing data. Demographics, medical care, employment, education, and socioeconomic status data were then extracted from linked administrative sources. RESULTS: We identified 1,040 individuals with these rare conditions: 125 with FXS, 695 with SB, and 220 with MD. The vast majority of the cases (95%) were identified in the Medicaid database. Half of the cohort was male, with a higher percentage in the FXS and MD groups. Sixty-two percent of the cohort was enrolled in the last year of high school. Over half of the cohort received support services from the state's disability and special-needs agency; 16% received food assistance. Thirty-eight percent were employed at some point during the study period. Forty-nine individuals with SB and 56 with MD died during the study period. CONCLUSIONS: We used a linked statewide data system to study rare conditions. Strengths include the diversity of information, rigorous identification strategies, and access to longitudinal data. Despite limitations inherent to administrative data, we found that linked state data systems are valuable resources for investigating important public health questions on rare conditions.

Electroarthrography: a novel method to assess articular cartilage and diagnose osteoarthritis by non-invasive measurement of load-induced electrical potentials at the surface of the knee.

OBJECTIVE: A new technique called electroarthrography (EAG) measures electrical potentials on the surface of the knee during joint loading. The objective of this study was to evaluate the effectiveness of EAG to assess joint cartilage degeneration. DESIGN: EAG recordings were performed on 20 asymptomatic subjects (Control group) and on 20 patients with bilateral knee osteoarthritis (OA) who had had a unilateral total knee replacement (TKR), both the TKR knee and the remaining knee were analyzed. EAG signals were recorded at eight electrode sites over one knee as the subjects shifted their weight from one leg to the other to achieve joint loading. The EAG signals were filtered, baseline-corrected and time-averaged. RESULTS: EAG repeatability was assessed with a test-retest protocol which showed statistically significant high intraclass correlation coefficients (ICC) for four electrode sites near the joint line. These sites also showed the highest mean EAG values. The mean EAG potentials of the Control group were significantly higher compared with the OA group for three sites overlying the joint line. The potentials overlying the TKR were statistically nul. In the Control group, no statistically significant correlation was found between the EAG amplitude and age, weight, height or body mass index (BMI); no statistical difference was found in mean EAG potentials between women and men. CONCLUSIONS: This study indicates that EAG signals arise from the streaming potentials in compressed articular cartilage which are known sensitive indicators of joint cartilage health. EAG is a promising new technique for the non-invasive assessment of cartilage degeneration and arthritis.

Pre-pregnancy body mass index, weight change during pregnancy, and risk of intellectual disability in children.

OBJECTIVE: This study investigated pre-pregnancy body mass index (BMI) and weight change in pregnancy as potential risk factors for intellectual disability (ID) in children. DESIGN: Retrospective cohort study. SETTING: South Carolina, USA. POPULATION: A total of 78,675 mother-child pairs, insured by the South Carolina Medicaid programme, born in the period 2004-2007. METHODS: We analysed South Carolina Medicaid data, linked to data from both the South Carolina Department of Education (DOE) and the South Carolina Department of Disabilities and Special Needs (DDSN). Maternal pre-pregnancy BMI and weight change during pregnancy were obtained from birth certificates. ID cases were identified from the three sources listed above. We used generalised estimating equation logistic regression models to model the odds of ID in children. MAIN OUTCOME MEASURES: Identified as having ID in special education, DDSN, or Medicaid billing records. RESULTS: The risk of ID was greater in children of women with pre-pregnancy obesity, and the risk was greatest in children born to women with morbid obesity (OR 1.52, 95% CI 1.30-1.77 for ID of any severity; OR 1.73, 95% CI 1.23-2.45 for severe ID). Gestational weight change (gain or loss) was not significantly associated with odds of ID. CONCLUSIONS: Pre-pregnancy obesity may be a modifiable risk factor for ID in children, although further study is needed to evaluate whether the association meets criteria for causation.

Retail firewood can transport live tree pests.

Untreated firewood can harbor destructive insects and pathogens and transport them to uninfested areas. In a national survey of retail locations selling firewood in 18 states, over half (52%) of the firewood was from sources out of the purchase state and 50% showed evidence of insect infestation. In a three state survey of southern Rocky Mountain retailers, the most common retailer types carrying firewood were grocery stores and department or big box stores followed by gas stations or convenience stores. In 2007-2009, we purchased 419 firewood bundles from retailers in Colorado, New Mexico, Utah, and Wyoming and caged the firewood to quantify insect emergence. Live insects emerged from 47% of firewood bundles over 18 mo of rearing time. Approximately 11 insects emerged on average from each infested bundle (1-520 per bundle). Pine, fir, and mixed-conifer bundles yielded the greatest number of insects. Beetles (Coleoptera) were prominent and made up the majority of individuals (3-60 individuals in each of 24 families). Most Coleoptera were bark and ambrosia beetles (subfamily Scolytinae) while wood borers (Buprestidae, Cerambycidae, Siricidae) occurred in lower numbers. Firewood with evidence of previous or current insect infestation was more likely to have insects emerge than firewood without such evidence. The risk of moving live native or nonindigenous insects in untreated firewood is high because insects emerged up to 558 d from purchase date. Retail firewood should be heat treated in a manner to eliminate insects that is uniformly accepted across North America.

Prepopulated radiology report templates: a prospective analysis of error rate and turnaround time.

Current speech recognition software allows exam-specific standard reports to be prepopulated into the dictation field based on the radiology information system procedure code. While it is thought that prepopulating reports can decrease the time required to dictate a study and the overall number of errors in the final report, this hypothesis has not been studied in a clinical setting. A prospective study was performed. During the first week, radiologists dictated all studies using prepopulated standard reports. During the second week, all studies were dictated after prepopulated reports had been disabled. Final radiology reports were evaluated for 11 different types of errors. Each error within a report was classified individually. The median time required to dictate an exam was compared between the 2 weeks. There were 12,387 reports dictated during the study, of which, 1,173 randomly distributed reports were analyzed for errors. There was no difference in the number of errors per report between the 2 weeks; however, radiologists overwhelmingly preferred using a standard report both weeks. Grammatical errors were by far the most common error type, followed by missense errors and errors of omission. There was no significant difference in the median dictation time when comparing studies performed each week. The use of prepopulated reports does not alone affect the error rate or dictation time of radiology reports. While it is a useful feature for radiologists, it must be coupled with other strategies in order to decrease errors.

Early prediction of cardiac allograft vasculopathy and heart transplant failure.

Early risk-prediction is essential to prevent cardiac allograft vasculopathy (CAV) and graft failure in heart transplant patients. We developed multivariate models to identify patients likely to experience CAV, severe CAV, and failure due to CAV, at 1, 5 and 10 years. A cohort of 172 patients was followed prospectively for 6.7 ± 3.9 years. Logistic regression models were developed and cross-validated using bootstrap resampling. Predictive markers of atherothrombosis (myocardial fibrin deposition, and loss of vascular antithrombin and tissue plasminogen activator) and arterial endothelial activation (intercellular adhesion molecule-1 expression) were measured in serial biopsies obtained within 3 months posttransplant. Most markers were univariately associated with outcome. Multivariate models showed that loss of tissue plasminogen activator was the dominant and, in most cases, only predictor of long-term CAV (p < 0.001), severe CAV (p < 0.001), and graft failure due to CAV (p < 0.001). The models discriminated patients having adverse outcomes, had particularly high negative predictive values (graft failure due to CAV: 99%, 99% and 95% at 1, 5 and 10 years) and predicted event incidence and time to event. Early absence of atherothrombotic risk identifies a patient subgroup that rarely develops CAV or graft failure, implying that this low-risk subgroup could possibly be followed with fewer invasive procedures.

Application of biomarkers in the development of drugs intended for the treatment of osteoarthritis.

OBJECTIVE: Osteoarthritis (OA) is a chronic and slowly progressive disease for which biomarkers may be able to provide a more rapid indication of therapeutic responses to therapy than is currently available; this could accelerate and facilitate OA drug discovery and development programs. The goal of this document is to provide a summary and guide to the application of in vitro (biochemical and other soluble) biomarkers in the development of drugs for OA and to outline and stimulate a research agenda that will further this goal. METHODS: The Biomarkers Working Group representing experts in the field of OA biomarker research from both academia and industry developed this consensus document between 2007 and 2009 at the behest of the Osteoarthritis Research Society International Federal Drug Administration initiative (OARSI FDA initiative). RESULTS: This document summarizes definitions and classification systems for biomarkers, the current outcome measures used in OA clinical trials, applications and potential utility of biomarkers for development of OA therapeutics, the current state of qualification of OA-related biomarkers, pathways for biomarker qualification, critical needs to advance the use of biomarkers for drug development, recommendations regarding practices and clinical trials, and a research agenda to advance the science of OA-related biomarkers. CONCLUSIONS: Although many OA-related biomarkers are currently available they exist in various states of qualification and validation. The biomarkers that are likely to have the earliest beneficial impact on clinical trials fall into two general categories, those that will allow targeting of subjects most likely to either respond and/or progress (prognostic value) within a reasonable and manageable time frame for a clinical study (for instance within 1-2 years for an OA trial), and those that provide early feedback for preclinical decision-making and for trial organizers that a drug is having the desired biochemical effect. As in vitro biomarkers are increasingly investigated in the context of specific drug treatments, advances in the field can be expected that will lead to rapid expansion of the list of available biomarkers with increasing understanding of the molecular processes that they represent.

Cooperative regulation of AJM-1 controls junctional integrity in Caenorhabditis elegans epithelia.

The function of epithelial cell sheets depends on the integrity of specialized cell-cell junctions that connect neighbouring cells. We have characterized the novel coiled-coil protein AJM-1, which localizes to an apical junctional domain of Caenorhabditis elegans epithelia basal to the HMR-HMP (cadherin-catenin) complex. In the absence of AJM-1, the integrity of this domain is compromised. Proper AJM-1 localization requires LET-413 and DLG-1, homologues of the Drosophila tumour suppressors Scribble and Discs large, respectively. DLG-1 physically interacts with AJM-1 and is required for its normal apical distribution, and LET-413 mediates the rapid accumulation of both DLG-1 and AJM-1 in the apical domain. In the absence of both dlg-1 and let-413 function AJM-1 is almost completely lost from apical junctions in embryos, whereas HMP-1 (alpha-catenin) localization is only mildly affected. We conclude that LET-413 and DLG-1 cooperatively control AJM-1 localization and that AJM-1 controls the integrity of a distinct apical junctional domain in C. elegans.

A subset of lupus anti-DNA antibodies cross-reacts with the NR2 glutamate receptor in systemic lupus erythematosus.

In systemic lupus erythematosus, antibodies against double-stranded DNA are a major contributor to renal disease. We have previously demonstrated that the pentapeptide Asp/Glu-Trp-Asp/Glu-Tyr-Ser/Gly is a molecular mimic of double-stranded DNA. This sequence is also present in the extracellular domain of murine and human NMDA (N-methyl-D-aspartate) receptor subunits NR2a and NR2b. Here we show that the NR2 receptor is recognized by both murine and human anti-DNA antibodies. Moreover, anti-DNA antibodies with this cross-reactivity mediate apoptotic death of neurons in vivo and in vitro. Finally, we show that the cerebrospinal fluid of a patient with systemic lupus erythematosus contains these antibodies and also mediates neuronal death via an apoptotic pathway. These observations indicate that lupus antibodies cross-react with DNA and NMDA receptors, gain access to cerebrospinal fluid and may mediate non-thrombotic and non-vasculitic abnormalities of the central nervous system.

Efficacy of ozone fumigation against the major grain pests in stored wheat.

Field experiments were conducted in steel bins containing 13,600 kg of hard red winter wheat, Triiticum aestivum L. One bin was treated with ozone and the second bin served as a control. Stored grain insects were placed in bins for 1-, 2-, 3-, and 4-d exposure periods in sampling tubes to test ozone concentrations of 0, 25, 50, and 70 parts per million by volume (ppmv). Ozone treatments on eggs and larvae of Plodia interpunctella (Hübner) were not effective, but pupae were more susceptible. Sitophilus oryzae (L.) adults were the most susceptible species with 100% mortality reached after 2 d in all ozone treatments. However, some progeny were produced at all concentrations and exposure periods. Tribolium castaneum (Herbst) adults had 100% mortality only after 4 d at 50 or 70 ppmv. No T. castaneum progeny were produced after 2-4 d at 70 ppmv. For Rhyzopertha dominica (F.), Cryptolestes ferrugineus (Stephens), and Oryzaephilus surinamensis (L.), 100% mortality was never achieved and progeny were produced at all ozone concentrations. Laboratory experiments, testing the effectiveness of ozone in controlling psocids, were conducted in two polyvinyl chloride cylinders each containing 55 kg of hard red winter wheat. Ozone treatment at a concentration of 70 ppmv was highly effective against adult female Liposcelis bostrychophila Badonnel and Liposcelis paeta Pearman after only 1 d of exposure. However, it was not effective against eggs of both species at all exposure periods. Ozonation has potential for the control of some stored grain insect pests on wheat.

Induction of autoreactive B cells allows priming of autoreactive T cells.

A novel mechanism for breaking T cell self tolerance is described. B cells induced to make autoantibody by immunization of mice with the non-self protein human cytochrome c can present the self protein mouse cytochrome c to autoreactive T cells in immunogenic form. This mechanism of breaking T cell self tolerance could account for the role of foreign antigens in breaking not only B cell but also T cell self tolerance, leading to sustained autoantibody production in the absence of the foreign antigen.

Predictors of need-driven behaviors in nursing home residents with dementia and associated certified nursing assistant burden.

OBJECTIVE: We examined predictors of staff-reported need-driven behaviors and resistiveness to care in nursing home residents with dementia and predictors of certified nursing assistant (CNA) burden related to both constructs. Background and proximal factors from the need-driven dementia-compromised behavior model [Algase, D.L., Beck, C., Kolanowski, A., Whall, A., Berent, S., Richards, K., et al. (1996). Need-driven dementia-compromised behavior: An alternative view of disruptive behavior. American Journal of Alzheimer's Disease, 5, 10-19] were examined as potential predictors of need-driven behaviors (NDBs) and resistiveness to care and CNA burden. METHOD: We used secondary data analysis of prospective data from 10 nursing homes in Birmingham, Alabama. One-hundred and sixty-one residents (83.43 +/- 8.56 years) with mini mental state examination (MMSE) score = 6.41 (+/- 6.66) were assessed via chart review, resident surveys, and surveys of CNAs. RESULTS: Multiple regression models revealed that cognitive functioning, activities of daily living functioning, race, gender, and CNA-reported weekly resident pain intensity were associated with resident NDBs. Regression models also revealed that weekly pain intensity and medical comorbidity were associated with CNA burden associated with the resident NDBs. However, we were unable to explain a significant amount of variance in the resistiveness to care or CNA burden associated with resistiveness to care. DISCUSSION: Results underscore the role of pain in both resident NDBs and associated CNA burden. Future research should focus on predictors of resident resistiveness to care and the relation of pain assessment and management practices to CNA burden. Moreover, interventions to improve resident care should seek to include CNAs in institutional pain assessment and management processes.

Systemic retinoids: chemoprevention of skin cancer in transplant recipients.

Solid organ transplant recipients (OTRs) have an increased incidence of skin cancer, resulting in significant morbidity and mortality post-transplantation. Chemoprevention strategies are focused on reducing and delaying the development of skin cancer in these patients. Although systemic retinoids are widely used in OTRs, few randomized controlled trials have been performed. Limited data suggest that acitretin may have a beneficial role in high-risk OTRs. Since rebound flares occur upon discontinuation of retinoids, chemoprevention should be viewed as a lifelong therapy. Further studies are required to establish the efficacy and long-term safety of systemic retinoids as chemopreventive agents for high-risk transplant recipients.

Ultrastructural localization of dialyzed iron-reactive mucosubstance in rabbit heterophils, basophils, and eosinophils.

For ultrastructural localization of acid mucosubstances in rabbit granulocytes, bone marrow and buffy coat specimens were fixed with formalin, glutaraldehyde, or osmium tetroxide, sectioned at 40 micro, and stained with the Rinehart and Abul-Haj solution of dialyzed iron (DI). Heterophils revealed DI staining on the outer surface of the plasma membrane, in the Golgi complex involved in primary granulogenesis, and in primary granules. The intragranular distribution of DI-stained material varied at different stages in the maturation of primary granules. Immature granules of heterophils fixed by any of the three methods contained a peripheral concentric band of DI-positive material; however, fully mature primary granules possessed a core of DI-reactive material in heterophils fixed with osmium tetroxide, but they contained little or no staining in heterophils fixed with formalin or glutaraldehyde. Secondary granules of rabbit heterophils failed to stain with DI. Tertiary granules, observed only in late heterophils, contained distinct DI-positive particles. Basophil granules exhibited intensely DI-stained material distributed in an orderly pattern throughout the granule. In eosinophils, DI staining was localized in the Golgi complex and in the rims of a few immature cytoplasmic granules.

Simultaneous synthesis of histone and DNA in synchronously dividing Tetrahymena pyriformis.

Histone and DNA syntheses have been studied in synchronously dividing Tetrahymena pyriformis GL. During the heat treatment necessary to synchronize cultures of this amicronucleate protozoan, the DNA content of the already polyploid macronucleus increases. When the cells begin synchronous division, their DNA content is reduced in a stepwise process which is closely paralleled by reduction of macronuclear histone content. During cell division, the contents of DNA and histone decrease by slightly more than twofold, and in the subsequent S phase, DNA and histone increase simultaneously to 85% of the values expected if all chromosomes were to double. The first step in the process of reduction of DNA and histone contents is their decrease in excess of twofold, and this is accomplished by removal of extrusion bodies from the nuclei of dividing cells. The second step is a mechanism which allows, in effect, only 70% of the chromatin in the average nucleus to duplicate. Such partial duplication suggests that both histone and DNA syntheses in synchronous Tetrahymena depend upon a regulatory mechanism, the mediating elements of which are localized in only certain chromosomes.

A putative catenin-cadherin system mediates morphogenesis of the Caenorhabditis elegans embryo.

During morphogenesis of the Caenorhabditis elegans embryo, hypodermal (or epidermal) cells migrate to enclose the embryo in an epithelium and, subsequently, change shape coordinately to elongate the body (Priess, J.R., and D.I. Hirsh. 1986. Dev. Biol. 117:156- 173; Williams-Masson, E.M., A.N. Malik, and J. Hardin. 1997. Development [Camb.]. 124:2889-2901). We have isolated mutants defective in morphogenesis that identify three genes required for both cell migration during body enclosure and cell shape change during body elongation. Analyses of hmp-1, hmp-2, and hmr-1 mutants suggest that products of these genes anchor contractile actin filament bundles at the adherens junctions between hypodermal cells and, thereby, transmit the force of bundle contraction into cell shape change. The protein products of all three genes localize to hypodermal adherens junctions in embryos. The sequences of the predicted HMP-1, HMP-2, and HMR-1 proteins are related to the cell adhesion proteins alpha-catenin, beta-catenin/Armadillo, and classical cadherin, respectively. This putative catenin-cadherin system is not essential for general cell adhesion in the C. elegans embryo, but rather mediates specific aspects of morphogenetic cell shape change and cytoskeletal organization.

Increased prevalence of cardiovascular defects among 56,709 California twin pairs.

This study compared the prevalence of cardiovascular defects in twin and singleton births and explored the influences of zygosity (monozygotic and dizygotic) and maternal age (<35 and >or=35 years of age) on concordance. Data on twin and singleton infants with (n = 628 twin pairs and n = 14,078 singletons) and without (n = 53,974 twin pairs and n = 4,858,255 singletons) cardiovascular defects were obtained from the California Birth Defects Monitoring Program and the California vital statistics birth and fetal death records during the period 1983-2003. Prevalence ratios (PR) (prevalence of twin/singleton) and approximate 95% confidence intervals were calculated for 16 congenital cardiovascular categories. Poisson regression techniques using log-linear models were employed to assess whether the probability of concordance of defects within each cardiovascular category varied by zygosity or maternal age. An increased prevalence was observed in twins compared to singletons in all 16 cardiovascular categories. Seven of the cardiovascular categories had at least double the prevalence in twins compared to singletons. Like-sex twins, as a proxy of monozygosity, had an increased prevalence of cardiovascular defects compared to unlike sex twins. Probabilities of concordance for flow lesions were higher among monozygotic than dizygotic twins. Our study provides evidence that twinning is associated with more cardiovascular defects than singletons. Increased concordance for flow lesions in monozygotic twins was observed, an observation that is in agreement with findings from familial recurrence studies of cardiovascular defects.