Design of a Multicenter Randomized Controlled Trial comparing the effectiveness of shared decision making versus motivational interviewing plus cognitive behavioral therapy for voluntary opioid tapering: The INSPIRE study protocol.
This paper describes the design and protocol of a pragmatic, randomized trial to evaluate the comparative effectiveness of shared decision making versus motivational interviewing plus cognitive behavioral therapy for chronic pain for the voluntary tapering of opioid dose in adults with chronic noncancer pain. Integrated Services for Pain: Interventions to Reduce Pain Effectively (INSPIRE) is a multicenter, randomized trial conducted at three academic health centers in the southeastern United States. Participants are adults receiving long-term opioid therapy of at least 20 morphine milligram equivalents daily for chronic noncancer pain. Participants were randomized to either the shared decision-making intervention or the motivational interviewing session and cognitive behavioral therapy for chronic pain intervention. All participants also received guideline-concordant care supporting opioid pharmacotherapy. The primary outcome was change from baseline in average daily prescribed opioid dose at 12 months, using prescribing data from electronic health records. Secondary outcomes were Patient-Reported Outcomes Measurement Information System Pain Interference and Physical Function at 12 months. This trial evaluates the comparative effectiveness of shared decision making versus motivational interviewing plus cognitive behavioral therapy for chronic pain for the voluntary tapering of opioid dose in adults with chronic noncancer pain. Results from this study can guide clinicians, researchers, and policymakers as they seek to reduce opioid prescribing and improve management of chronic pain. NCT03454555. ClinicalTrials.gov Identifier: NCT03454555 (https://clinicaltrials.gov/ct2/show/record/NCT03454555). Participant enrollment began on June 26, 2019.


Nictitating membrane as a potentially useful postmortem diagnostic specimen for classical swine fever.
The gold standard for diagnosis of classical swine fever (CSF) is cell culture virus isolation combined with reverse transcriptase-polymerase chain reaction (RT-PCR) and fluorescent antibody test (FAT) in cryosections of tonsils, spleen, various lymph nodes, ileum, and kidney. Autolytic and heterolytic samples render correct FAT evaluation difficult and can even yield false-negative or ambiguously positive results. To extend the spectrum of CSF diagnostic specimens, the authors tested whether the nictitating membrane (NM) might be a useful adjunct diagnostic specimen in wild boars and domestic pigs. To accomplish this, results of virus isolation, FAT, and RT-PCR were compared on NM samples and lymphoid tissues, which are the routine specimens of choice for CSF diagnosis. Wild boars (n = 30) and domestic pigs (n = 8) were experimentally challenged with various CSF virus (CSFV) strains or isolates of different virulence. The FAT revealed CSFV antigen in surface and tubular adenoid epithelium as well as in lymphatic follicles of the NM. In wild boars and domestic pigs with CSF, a strong agreement was found between results of FAT, virus isolation, and RT-PCR on NM and lymphoid tissues. These results suggest that NM is a useful additional specimen that can provide valuable data for postmortem diagnosis of CSF. The NM is relatively easy to sample at necropsy, and postmortem autolysis and heterolysis of this tissue is minimal compared with internal organs.


Comparative studies of xanthine oxidase inhibitors viz. allopurinol and febuxostat against induced hyperuricaemia in a poultry model.
In this study, an attempt was made to evaluate the relative efficacy of two important anti-gout agents, viz. allopurinol and febuxostat, in the control of hyperuricaemia/gout using a poultry model. A 21-day study was conducted on 48 Vencobb-400 broiler chicks randomly divided into four groups. In one group hyperuricaemia/gout was induced by the oral administration of diclofenac (group D); in two other groups the ameliorative effect of the two drugs under study was investigated by providing both simultaneously, i.e. diclofenac and allopurinol (group DA), diclofenac and febuxostat (group DF); and the fourth group was kept un-induced and untreated as a control (group C). Both allopurinol and febuxostat inhibit xanthine oxidase enzymes, thereby reducing the production of uric acid. The birds kept on diclofenac alone exhibited the highest level of hyperuricaemia, clinical signs of gout, and overt adverse changes in the visceral organs, whereas these changes were lesser in allopurinol- and febuxostat-treated groups. Furthermore, haematological, biochemical, patho-morphological, and ultra-structural studies using transmission electron microscopy were carried out to evaluate the pathology and, thus, the ameliorative effect of allopurinol and febuxostat. The findings proved that allopurinol and febuxostat carry definite ameliorative potential as anti-hyperuricemic and anti-gout agents in poultry, which was better expressed by febuxostat compared to allopurinol.


Occupational and environmental health nursing: ethics and professionalism.
This article provides an overview of ethical issues related to the practice of occupational and environmental health nursing and possible strategies for resolution. Also, professionalism related to professional growth and advancing the specialty is discussed.


Key metabolic pathways involved in xenobiotic biotransformation and stress responses revealed by transcriptomics of the mangrove oyster Crassostrea brasiliana.
The Brazilian oyster Crassostrea brasiliana was challenged to three common environmental contaminants: phenanthrene, diesel fuel water-accommodated fraction (WAF) and domestic sewage. Total RNA was extracted from the gill and digestive gland, and cDNA libraries were sequenced using the 454 FLX platform. The assembled transcriptome resulted in ̃20,000 contigs, which were annotated to produce the first de novo transcriptome for C. brasiliana. Sequences were screened to identify genes potentially involved in the biotransformation of xenobiotics and associated antioxidant defence mechanisms. These gene families included those of the cytochrome P450 (CYP450), 70kDa heat shock, antioxidants, such as glutathione S-transferase, superoxide dismutase, catalase and also multi-drug resistance proteins. Analysis showed that the massive expansion of the CYP450 and HSP70 family due to gene duplication identified in the Crassostrea gigas genome also occurred in C. brasiliana, suggesting these processes form the base of the Crassostrea lineage. Preliminary expression analyses revealed several candidates biomarker genes that were up-regulated during each of the three treatments, suggesting the potential for environmental monitoring.


The WHO ultrasonography protocol for assessing hepatic morbidity due to Schistosoma mansoni. Acceptance and evolution over 12 years.
The aim of this study is to review the worldwide acceptance of the World Health Organization (WHO) ultrasound protocol for assessing hepatosplenic morbidity due to Schistosoma mansoni since its publication in 2000. A PubMed literature research using the keywords "schistosomiasis and ultrasound," "schistosomiasis and ultrasonography," and "S. mansoni and ultrasound" from 2001 to 2012 was performed. Case reports, reviews, reports on abnormalities due to parasites other than S. mansoni, organ involvement other than the human liver, and reports where ultrasound method was not described were excluded. Six studies were retrieved from other Brazilian sources. Sixty studies on 37,424 patients from 15 countries were analyzed. The WHO protocol was applied with increasing frequency from 43.75% in the years 2001 to 2004 to 84.61% in 2009 to 2012. Results obtained using the pictorial image pattern approach of the protocol are reported in 38/41 studies, whereas measurements of portal branch walls were applied in 19/41 and results reported in 2/41 studies only. The practical usefulness of the pictorial approach of the WHO protocol is confirmed by its wide acceptance. This approach alone proved satisfactory in terms of reproducibility, assessment of evolution of pathology, and comparability between different settings. The measurements of portal branches, also part of the protocol, may be omitted without losing relevant information since results obtained by these measurements are nonspecific. This would save resources by reducing the time required for each examination. It is also more feasible for examiners who are not specialized in medical imaging. As with all protocols, incipient liver fibrosis is difficult to distinguish from normal ultrasound findings of the liver. The ability of this protocol to predict complications in severe cases should be further evaluated in a higher number of patients.


Farm factors associated with the use of antibiotics in pig production.
The aim of this study was to investigate farm-level economic and technical factors that are associated with the use of antibiotics on pig farms. Identification of such factors, like farm size and net farm result, may help to increase epidemiological knowledge and to specify farm advice and policy making to reduce inappropriate use of antibiotics. The study used over 300 farm-year records collected during 2004 to 2007 from pig farms in the Netherlands. Data included economic and technical factors as well as antibiotic administration. Data were statistically analyzed for factors associated with antibiotic use, both for fattening pig and sow farms (piglets only), separately. The response variable was the average number of daily dosages per average pig year. Statistical analysis was performed on 16 and 19 potential explanatory factors for the fattening pig and sow farms, respectively. The results showed that, both on the fattening pig and sow farms, the average use of antibiotics increased from 2004 to 2006, but decreased during 2007, but the effect of year was not significant (P > 0.05). Use of antibiotics varied between individual farms. Large farm repeatability for the use of antibiotics in the different years was found. Factors associated (P < 0.05) with the use of antibiotics included: farm system, number of pigs, and population density in the region of the farm (for sow farms only). As these factors are easy to collect and to register, they can be used to specify farm advice and investigation, as well as for policy making. The majority of the technical and economic factors were not significantly (P > 0.05) related to the on-farm use of antibiotics. Therefore, it is recommended to focus future research on the potential role of socioeconomic factors associated with antibiotic use on pig farms.


Long-term therapy with adefovir dipivoxil in hepatitis B e antigen-negative patients developing resistance to lamivudine.
The efficacy of long-term adefovir dipivoxil monotherapy or combination of adefovir and lamivudine in hepatitis B e antigen (HBe-Ag)-negative lamivudine-resistant chronic hepatitis B (CHB) patients is still under investigation. To assess the safety and efficacy of the long-term adefovir treatment alone or in combination with lamivudine in HBe-Ag-negative CHB patients who had developed breakthrough because of lamivudine-resistant mutants. Fifty-nine patients received combination therapy, while 23 switched to adefovir alone after a 3-month course of combination therapy. The median follow-up after adefovir's onset was 31 (18-40) months. Baseline characteristics were similar between the two groups. At 12 and 24 months, 69% and 89% of patients receiving combination therapy and 73% and 82% of patients receiving adefovir monotherapy had serum HBV-DNA <10(4) copies/mL (P > 0.5). Normalization of alanine aminotransferase levels occurred in 81% and 79% of patients receiving combination vs. 61% and 53% receiving adefovir monotherapy at 12 and 24 months, respectively (P > 0.50). Virological breakthroughs because of adefovir-resistant mutants occurred in five patients under adefovir monotherapy and in none receiving combination therapy (P = 0.001). No one developed decompensated liver disease or hepatocellular carcinoma during follow-up. Re-introduction of lamivudine in adefovir-resistant patients achieved reduction in HBV-DNA and biochemical remission, but re-emergence of lamivudine mutants was observed in one patient after 7.5 months. In HBe-Ag-negative CHB patients with lamivudine resistance, adding adefovir to continuing lamivudine therapy maximizes anti-viral efficacy because of absence of viral resistance.


Anemia and risk of dementia in older adults: findings from the Health ABC study.
To determine whether anemia is associated with incident dementia in older adults. We studied 2,552 older adults (mean age 76.1 years; 38.9% black; 51.8% female) participating in the Health, Aging, and Body Composition study and free of dementia at baseline. We defined anemia using WHO criteria (hemoglobin concentration <13 g/dL for men and <12 g/dL for women). Dementia diagnosis was determined by dementia medication use, hospital records, or a change in modified mini-mental state (3MS) score of more than 1.5 SD from mean. Discrete time Cox proportional hazard regression models were used to examine the hazard for developing dementia associated with anemia. Of 2,552 participants, 393 (15.4%) older adults had anemia at baseline [corrected]. Over 11 years of follow-up, 455 (17.8%) participants developed dementia. In the unadjusted model, those with baseline anemia had an increased risk of dementia (23% vs. 17%, hazard ratio = 1.64; 95% confidence interval 1.30, 2.07) compared to those without anemia. The association remained significant after adjusting for demographics, APOE ε4, baseline 3MS score, comorbidities, and renal function. Additional adjustment for other anemia measures (mean corpuscular volume, red cell distribution width), erythropoietin, and C-reactive protein did not appreciably change the results. There was no interaction by sex and race on risk of developing dementia. Among older adults, anemia is associated with an increased risk of developing dementia. Findings suggest that further study of anemia as a risk factor for dementia and a target for intervention for cognitive health is warranted.


Favipiravir inhibits in vitro Usutu virus replication and delays disease progression in an infection model in mice.
Usutu virus (USUV) is an emerging flavivirus that causes Usutu disease mainly in birds, but infection of mammals such as rodents, bats and horses has also been demonstrated. In addition, human cases (both in immunocompromised and -competent individuals) were also reported. Large outbreaks with other flaviviruses, such as West Nile virus and Zika virus, indicate that one should be vigilant for yet other outbreaks. To allow the identification of inhibitors of USUV replication, we established in vitro antiviral assays, which were validated using a small selection of known flavivirus inhibitors, including the broad-spectrum viral RNA polymerase inhibitor favipiravir (T-705). Next, an USUV infection model in AG129 (IFN-α/β and IFN-γ receptor knockout) mice was established. AG129 mice proved highly susceptible to USUV; an inoculum as low as 102 PFU (1.3 × 105 TCID50) resulted in the development of symptoms as early as 3 days post infection with viral RNA being detectable in various tissues. Treatment of mice with favipiravir (150 mg/kg/dose, BID, oral gavage) significantly reduced viral load in blood and tissues and significantly delayed virus-induced disease. This USUV mouse model is thus amenable for assessing the potential in vivo efficacy of (novel) USUV/flavivirus inhibitors.


Antibodies to the alpha-subunit of insulin receptor from eggs of immunized hens.
Simple methods for the generation, purification, and assay of antibodies to the alpha-subunit of insulin receptor from eggs of immunized hens have been described. Chicken antibodies against the alpha-subunit inhibit insulin binding to the receptor and stimulate glucose oxidation as well as autophosphorylation of the beta-subunit. Thus the properties of chicken antibodies are very similar to those of antibodies found in human autoimmune diseases and different from rabbit antibodies obtained against the same antigen.


Detecting sleep apnoea syndrome in primary care with screening questionnaires and the Epworth sleepiness scale.
To examine the utility of apnoea screening questionnaires, alone and in combination with the Epworth sleepiness scale (ESS), for detecting obstructive sleep apnoea (OSA) in primary care. Prospective validation study in an Australian general population cohort. 424 of 772 randomly invited Tasmanian Longitudinal Health Study, 6th decade follow-up participants with OSA symptoms (mean age, 52.9 years; SD, 0.9 year) who completed OSA screening questionnaires and underwent type 4 sleep studies. Clinically relevant OSA, defined as moderate to severe OSA (15 or more oxygen desaturation events/hour), or mild OSA (5-14 events/hour) and excessive daytime sleepiness (ESS ≥ 8); diagnostic test properties of the Berlin (BQ), STOP-Bang and OSA-50 questionnaires, alone or combined with an ESS ≥ 8. STOP-Bang and OSA-50 correctly identified most participants with clinically relevant OSA (sensitivity, 81% and 86% respectively), but with poor specificity (36% and 21% respectively); the specificity (59%) and sensitivity of the BQ (65%) were both low. When combined with the criterion ESS ≥ 8, the specificity of each questionnaire was high (94-96%), but sensitivity was low (36-51%). Sensitivity and specificity could be adjusted according to specific needs by varying the STOP-Bang cut-off score when combined with the ESS ≥ 8 criterion. For people likely to trigger OSA assessment in primary care, the STOP-Bang, BQ, and OSA-50 questionnaires, combined with the ESS, can be used to rule in, but not to rule out clinically relevant OSA. Combined use of the STOP-Bang with different cut-off scores and the ESS facilitates a flexible balance between sensitivity and specificity.


Characterizing and predicting person-specific, day-to-day, fluctuations in walking behavior.
Despite the positive health effect of physical activity, one third of the world's population is estimated to be insufficiently active. Prior research has mainly investigated physical activity on an aggregate level over short periods of time, e.g., during 3 to 7 days at baseline and a few months later, post-intervention. To develop effective interventions, we need a better understanding of the temporal dynamics of physical activity. We proposed here an approach to studying walking behavior at "high-resolution" and by capturing the idiographic and day-to-day changes in walking behavior. We analyzed daily step count among 151 young adults with overweight or obesity who had worn an accelerometer for an average of 226 days (~25,000 observations). We then used a recursive partitioning algorithm to characterize patterns of change, here sudden behavioral gains and losses, over the course of the study. These behavioral gains or losses were defined as a 30% increase or reduction in steps relative to each participants' median level of steps lasting at least 7 days. After the identification of gains and losses, fluctuation intensity in steps from each participant's individual time series was computed with a dynamic complexity algorithm to identify potential early warning signals of sudden gains or losses. Results revealed that walking behavior change exhibits discontinuous changes that can be described as sudden gains and losses. On average, participants experienced six sudden gains or losses over the study. We also observed a significant and positive association between critical fluctuations in walking behavior, a form of early warning signals, and the subsequent occurrence of sudden behavioral losses in the next days. Altogether, this study suggests that walking behavior could be well understood under a dynamic paradigm. Results also provide support for the development of "just-in-time adaptive" behavioral interventions based on the detection of early warning signals for sudden behavioral losses.


Two-Dimensional Metal-Organic Framework Nanosheets as an Enzyme Inhibitor: Modulation of the α-Chymotrypsin Activity.
Two-dimensional metal-organic framework (MOF) nanosheets are utilized as effective enzyme inhibitors, providing an inspiring means to enhance the control of cellular processes as well as improve our understanding of the surface chemistry between MOFs and enzymes. In this paper, we demonstrated that the activity of α-chymotrypsin (ChT) can be effectively inhibited with 96.9% inhibition by 2-D Cu(bpy)2(OTf)2 nanosheets, while Zn2(bim)4 nanosheets show no significant inhibition effect toward ChT. Kinetic studies revealed that the material acts as a competitive inhibitor toward ChT. Furthermore, fluorescence and circular dichroism spectroscopy reveal that the 2-D MOF nanosheets do not change the secondary structure of the enzyme. The Cu(II) center of the 2-D nanosheets binds the 4-(2-hydroxyethyl)-1-piperazineethanesulfonic acid (HEPES) molecules in the buffer, leading to an electrostatic interaction between the nanosheets and the enzyme. In addition, the irreversible coordination interactions between Cu(II) center and His-57 played an important role during the inhibition process, as supported by ionic strength experiments and UV absorbance changes of Cu(II) d-d transitions. As a result, the substrate is prevented from reaching the active sites of the enzyme causing enzyme inhibition. The modulation of enzyme activity by 2-D MOF nanosheets opens up a new direction for the exploration of the MOF-bio interface in physiological and catalytic systems.


AlFe2-xCoxB2 (x = 0-0.30): TC Tuning through Co Substitution for a Promising Magnetocaloric Material Realized by Spark Plasma Sintering.
AlFe2B2 and AlFe2-xCoxB2 (x = 0-0.30) were synthesized from the elements in three different ways. The samples were characterized by powder X-ray diffraction, Rietveld refinements, energy-dispersive X-ray spectroscopy, and magnetic measurements. Using Al flux the formation of AlFe2B2 single crystals is preferred. Arc melting enables the substitution of ∼6% Co. This substitution of Fe by Co decreases the Curie temperature TC from 290 to 240 K. The highest Co substitution up to 15% is achieved by spark plasma sintering (SPS). TC is reduced to 205 K. In all cases an excess of Al is necessary to avoid the formation of ferromagnetic FeB. Al13Fe4-xCox is the common byproduct. TC and the cobalt content are linearly correlated. The transition paramagnetic-ferromagnetic remains sharp for all examples. The magnetic entropy change of the Co-containing samples is comparable to AlFe2B2. SPS synthesis yields, in short reaction times, a homogeneous and dense material with small amounts of paramagnetic Al13Fe4-xCox as an impurity, which can serve as sinter additive. These properties make AlFe2-xCoxB2 a promising magnetocaloric material for applications between room temperature and 200 K.


[Dementia with Lewy bodies].
Dementia with Lewy bodies (DLB), the second most frequent cause of primary degenerative dementias following Alzheimer's disease, has been increasingly recognized since the proposal of the consensus name and clinical diagnostic criteria. Although DLB overlaps in clinical, pathological, and genetic features with Alzheimer's disease and Parkinson's disease, DLB should be understood as an entity with the essential feature of the presence of Lewy bodies in the brain stem and cerebral cortex. From the clinical point of view, DLB is characterized by the presence of progressive dementia without severe memory disorders at the early stage, with significant cognitive fluctuations, well-formed recurrent visual hallucinations, and spontaneous Parkinsonism. This article reviews recent clinical and research findings, including our own, to facilitate clinical recognition of DLB. In addition to the supportive features described in the consortium clinical diagnostic criteria for DLB such as falls and great sensitivity to neuroleptic drugs, our studies found other frequent disorders including disproportionately severe visuoconstructive and visuoperceptual disturbances, transitory alterations in consciousness with reduplication phenomena, misidentification delusions, and non-aphasic misnamings. Neuroimaging features include relatively preserved hippocampal volume on MRI and occipital involvement on metabolic and blood flow imagings. The correct diagnosis of DLB is important to administer adequate treatment, to avoid adverse effects with neuroleptic drugs, and to establish precise prognosis. The present summary of the clinical features is hopefully helpful for clinical diagnosis of DLB. From a therapeutic point of view, cholinesterase inhibitors seemingly show some efficacy in the treatment of cognitive alterations. Further research would result in advances in diagnostic methods and therapeutic approaches in the near future.


Improved detection of enterotoxigenic Escherichia coli among patients with travelers' diarrhea, by use of the polymerase chain reaction technique.
This study sought to determine whether a specific polymerase chain reaction (PCR) for enterotoxigenic Escherichia coli (ETEC) toxins after chaotropic extraction of DNA from stool would increase the detection of ETEC over that of conventional oligonucleotide probe hybridization of 5 E. coli colonies per stool sample (a standard method). By DNA hybridization, 29 (21%) of 140 patients were positive for ETEC, and 59 (42%) of 140 were positive for ETEC when PCR was used. Sensitivity of the PCR assay was confirmed through spiked stool experiments to be approximately 100-1000 ETEC colonies per sample. Specificity of the assay was determined by showing an absence of ETEC by the PCR technique in a subgroup of 48 subjects and by confirming the presence of ETEC DNA of positive samples by dot blot procedure. PCR technique detected significantly more ETEC infections in these subjects than did the hybridization method (P<.0001).


A mathematical model of parasystole and its application to clinical arrhythmias.
A ventricular parasystolic focus capable of generating manifest ectopic beats should not be totally insulated from the electrical events that accompany depolarization in the surrounding tissue; the intrinsic cycle length of the ectopic discharge may be modulated by electrotonic influences transmitted across the zone of "protection." To study the nature of the interaction, response patterns were examined in a mathematical model programmed to simulate an ectopic pacemaker protected, but not divorced from ventricular responses to the normal pacemaker. Computer runs covered a wide range of heart rates, and a wide range of magnitudes of the simulated electrotonic influence. Application of the results obtained in the model to published examples of complex arrhythmias revealed a remarkably close fit to many clinical examples. This findings suggests that many patterns attributed to a re-entrant "extrasystolic" rhythm may, in fact, represent the modulated activity of a parasystolic focus.


Viral-like particles associated with naturally occurring transmissible venereal tumor in two dogs: preliminary report.
Naturally occurring canine transmissible venereal tumors in 2 dogs were examined ultrastructurally, using a transmission electron microscope. Typical nondegenerating cells of various shapes with normal cytoplasmic organellae were seen. Degenerating and necrotic cells characterized by loss of normal organellae with vacuolations of the cytoplasm were in all sections studied. Icosahedral electron-dense particles (22 nm diameter) were in the degenerating and necrotic cells. The uniqueness of this finding is not known. The shape and size of the particles indicate that there may be viral involvement.


Increased plasma concentrations of circulating intercellular adhesion molecule-1 (cICAM-1) in patients with necrotizing pancreatitis.
The intercellular adhesion molecule-1 (ICAM-1), a membrane glycoprotein, is important in the adhesion of cytokine-stimulated leukocytes to the endothelium of microvessels and their transendothelial migration. Circulating isoforms of ICAM-1 (cICAM-1) are known to be elevated in human serum as an indirect consequence of inflammatory responses. The aim of this study was to investigate whether cICAM-1 levels are elevated in patients with acute pancreatitis within 48 h of the onset of abdominal pain and whether cICAM-1 levels correlate with the severity of the tissue damage. Twenty-five consecutive patients admitted to a medical ICU had elevated cCAM-1 concentrations of 548 +/- 68 ng/ml, significantly different when compared to a control group of 18 healthy subjects (343 +/- 29; p = 0.018). According to the findings of contrast-enhanced CT or laparotomy patients were further divided in a group with acute edematous pancreatitis and a group with acute necrotizing pancreatitis. Pancreatic necrosis was associated with cICAM-1 levels of 729 +/- 106 ng/ml, significantly different from patients with mild disease (367 +/- 48) and controls (p < 0.001). Plasma cICAM-1 levels were not significantly different between healthy subjects and patients with mild pancreatitis. A significant correlation was found between cICAM-1 and C-reactive protein, an acute phase reactant and marker of necrotizing pancreatitis (r = 0.62; p < 0.01). The sensitivity and specificity for the detection of edematous or necrotizing pancreatitis of cICAM-1 plasma concentrations (cutoff point at 500 ng/ml) were 75% and 85%, respectively. These results suggest an enhanced release of ICAM-1 into plasma in the early stage of acute necrotizing pancreatitis. Leukocyte-endothelial cell adhesion may be associated with the inflammatory process of necrotizing tissue damage in acute pancreatitis. It could thus serve as a marker or predictor of a severe clinical course of pancreatitis.


Holding Ashley (X): Bestowing Identity Through Caregiving in Profound Intellectual Disability.
The controversy over the so-called Ashley Treatment (AT), a series of medical procedures that inhibited both growth and sexual development in the body of a profoundly intellectually impaired girl, usually centers either on Ashley's rights, including a right to an intact, unaltered body, or on Ashley's parents' rights to make decisions for her. The claim made by her parents, that the procedure would improve their ability to care for her, is often dismissed as inappropriate or, at best, irrelevant. We argue, however, that caregiving is a central issue in the controversy, as Ashley's need for caregiving is a defining characteristic of her life. In this article, we analyze the ethics of the Ashley Treatment within the context of family caregiving. Through the physical and emotional work of caregiving, families participate in the formation and maintenance of personal identity, a process that Hilde Lindemann recently called "holding." We argue that, in an intellectually disabled person such as Ashley, who depends on her family for every aspect of her care, the family's contribution to identity is an essential source of personhood. We believe that the treatment can be justified if it is indeed an instance of appropriate family "holding" for Ashley.


Adhesion-dependent regulation of an A+U-rich element-binding activity associated with AUF1.
Monocyte adherence results in the rapid transcriptional activation and mRNA stabilization of numerous mediators of inflammation and tissue repair. While the enhancer and promoter elements associated with transcriptional activation have been studied, mechanisms linking adhesion, mRNA stabilization, and translation are unknown. GROalpha and interleukin-1beta (IL-1beta) mRNAs are highly labile in nonadhered monocytes but stabilize rapidly after adherence. GROalpha and IL-1beta transcripts both contain A+U-rich elements (AREs) in the 3' untranslated region (UTR) which have been directly associated with rapid mRNA turnover. To determine if the GROalpha ARE region was recognized by factors associated with mRNA degradation, we carried out mobility gel shift analyses using a series of RNA probes encompassing the entire GROalpha transcript. Stable complexes were formed only with the proximal 3' UTR which contained the ARE region. The two slower-moving complexes were rapidly depleted following monocyte adherence but not direct integrin engagement. Deadherence reactivated the two largest ARE-binding complexes and destabilized IL-1beta transcripts. Antibody supershift studies demonstrated that both of these ARE RNA-binding complexes contained AUF1. The formation of these complexes and the accelerated mRNA turnover are phosphorylation-dependent events, as both are induced in adherent monocytes by the tyrosine kinase inhibitor genistein and the p38 MAP kinase inhibitor of IL-1beta translation, SK&F 86002. These results demonstrate that cell adhesion and deadhesion rapidly and reversibly modify both cytokine mRNA stability and the RNA-binding complexes associated with AUF1.


Comparative study of glycophorin A derived O-glycans from human Cad, Sd(a+) and Sd(a-) erythrocytes.
Glycophorin A was purified from the erythrocyte membranes of blood group Cad, Sd(a+) and Sd(a-) donors and the oligosaccharide alditols, obtained after alkaline borohydride degradation, separated by h.p.l.c. on an alkylamine silica gel column, were characterized by sugar analysis. Structure determination of the major acid components by methylation analysis, g.l.c.-m.s. and 1H-n.m.r. indicated that the three blood group Cad red cells under study (samples Cad., Bui. and Des.) carry the same pentasaccharide GalNAc(beta 1-4)[NeuAc(alpha 2-3)]Gal(beta 1-3)[NeuAc(alpha 2-6)]GalNAc -ol(Cad determinant) but in different amounts. This pentasaccharide, however, was absent from glycophorin A of Sd(a+) and Sd (a-) donors, suggesting that the Sda determinant is not associated with glycophorins. It was calculated that glycophorin A from the original Cad donor (Cad.) carries about 12 O-glycosidically linked pentasaccharide chains per molecule whereas only 2-3 of these chains were present in the samples from the two other unrelated Cad individuals (Bui. and Des.) It is well known from quantitative agglutination studies that the proportion of red cells which can be agglutinated by the Dolichos biflorus lectin varies from one Cad blood sample to another. Some are completely agglutinated (Cad. donor) whereas others are only partially agglutinated (Bui. and Des. donors) suggesting that some red cells might not carry the Cad determinants. From the results presented above and sodium dodecyl sulphate/polyacrylamide-gel electrophoresis studies it is suggested that Cad red cells from Bui. and Des. do not carry a mixture of glycophorin A molecules with or without the Cad pentasaccharides but a spectrum of glycoprotein molecules with varying amounts of Cad determinants.


Predator community and resource use jointly modulate the inducible defense response in body height of crucian carp.
Phenotypic plasticity can be expressed as changes in body shape in response to environmental variability. Crucian carp (Carassius carassius), a widespread cyprinid, displays remarkable plasticity in body morphology and increases body depth when exposed to cues from predators, suggesting the triggering of an antipredator defense mechanism. However, these morphological changes could also be related to resource use and foraging behavior, as an indirect effect of predator presence. In order to determine whether phenotypic plasticity in crucian carp is driven by a direct or indirect response to predation threat, we compared twelve fish communities inhabiting small lakes in southeast Norway grouped by four categories of predation regimes: no predator fish, or brown trout (Salmo trutta), perch (Perca fluviatilis), or pike (Esox lucius) as main piscivores. We predicted the body shape of crucian carp to be associated with the species composition of predator communities and that the presence of efficient piscivores would result in a deeper body shape. We use stable isotope analyses to test whether this variation in body shape was related to a shift in individual resource use-that is, littoral rather than pelagic resource use would favor the development of a specific body shape-or other environmental characteristics. The results showed that increasingly efficient predator communities induced progressively deeper body shape, larger body size, and lower population densities. Predator maximum gape size and individual trophic position were the best variables explaining crucian carp variation in body depth among predation categories, while littoral resource use did not have a clear effect. The gradient in predation pressure also corresponded to a shift in lake productivity. These results indicate that crucian carp have a fine-tuned morphological defense mechanism against predation risk, triggered by the combined effect of predator presence and resource availability.


Distributive justice in society and among peers: 8- to 14-year-olds' views on economic stratification inform their decisions about access to opportunities.
This study examined how children's and adolescents' beliefs about the distribution of wealth in society and the fairness of economic systems informed their behavior, judgments, and reasoning about access to opportunities among peers. The sample included 136 8- to 14-year-olds (47% girls, 60% White, majority middle- to higher-socioeconomic status [SES]) in the United States. Relative to older children, early adolescents viewed economic systems as less fair and wealth as less equally distributed, but still underestimated the true magnitude of existing economic disparities. Importantly, the stronger their system justification beliefs the fewer opportunities participants directed to poor peers over rich peers in an allocation scenario, but the more equally participants believed that wealth should be distributed in society the more opportunities they directed to poor peers. Moreover, participants were more supportive of allocating opportunities to poor peers when they had direct evidence that poor peers had been excluded in the past, and 40% reasoned explicitly about the implications of economic inequality when making their decision. Finally, exploratory associations of family SES and beliefs about distributive justice suggested that experiencing greater economic security may have enabled some participants to more readily critique societal inequality. Together, these findings provide correlational, experimental, and cross-sectional developmental evidence that older children's and early adolescents' beliefs about distributive justice in society inform their decisions about how to address disparities within their sphere of influence. (PsycInfo Database Record (c) 2021 APA, all rights reserved).


Identification and Expression Analysis of the C-TERMINALLY ENCODED PEPTIDE Family in Pisum sativum L.
The C-TERMINALLY ENCODED PEPTIDE(CEP) peptides play crucial roles in plant growth and response to environmental factors. These peptides were characterized as positive regulators of symbiotic nodule development in legume plants. However, little is known about the CEP peptide family in pea. Here, we discovered in pea genome 21 CEP genes (PsCEPs), among which three genes contained additional conserved motifs corresponding to the PIP (PAMP-induced secreted peptides) consensus sequences. We characterized the expression patterns of pea PsCEP genes based on transcriptomic data, and for six PsCEP genes with high expression levels in the root and symbiotic nodules the detailed expression analysis at different stages of symbiosis and in response to nitrate treatment was performed. We suggest that at least three PsCEP genes, PsCEP1, PsCEP7 and PsCEP2, could play a role in symbiotic nodule development, whereas the PsCEP1 and PsCEP13 genes, downregulated by nitrate addition, could be involved in regulation of nitrate-dependent processes in pea. Further functional studies are required to elucidate the functions of these PsCEP genes.


Proximal cell K+ activity: technical problems and dependence on plasma K+ concentration.
K+-selective liquid ion-exchanger double-barreled microelectrodes were used to measure intracellular K+ activity (alpha Ki) of proximal tubular cells in Necturus kidney. SEveral methodological problems inherent in the construction and in vivo application of such microelectrodes were considered, in particular the identification of leaky impalements and the correct assessment of alpha Ki during reversible perfusion of peritubular capillaries from control to a test solution. Peritubular potassium concentration (CpK) could be altered by means of double-barreled micropipettes containing a physiologic and a high or low K solution. The control alpha Ki value averaged 57.9 +/- 8.5 mM (mean +/- SD, n = 38) and the basolateral membrane potential was -70.4 +/- 5.8 mV. Thus, the K+ equilibrium potential across the basolateral membrane (EK) was -81.1 +/- 3.4 mV. Increasing CpK from 3.0 to 30.0 mM raised alpha Ki by 7.0 +/- 1.5 mM, and lowering CpK to 0.3 mM decreased alpha Ki by 9.2 +/- 2.9 mM. 1) the steady-state K+ distribution across the basolateral membrane indicates that potassium is actively pumped into the cell. 2) The relative stability of alpha Ki in the face of large CpK variations underscores the effectiveness of cell homeostasis; passive mechanisms appear to contribute to this end.


Brittle intermetallic compound makes ultrastrong low-density steel with large ductility.
Although steel has been the workhorse of the automotive industry since the 1920s, the share by weight of steel and iron in an average light vehicle is now gradually decreasing, from 68.1 per cent in 1995 to 60.1 per cent in 2011 (refs 1, 2). This has been driven by the low strength-to-weight ratio (specific strength) of iron and steel, and the desire to improve such mechanical properties with other materials. Recently, high-aluminium low-density steels have been actively studied as a means of increasing the specific strength of an alloy by reducing its density. But with increasing aluminium content a problem is encountered: brittle intermetallic compounds can form in the resulting alloys, leading to poor ductility. Here we show that an FeAl-type brittle but hard intermetallic compound (B2) can be effectively used as a strengthening second phase in high-aluminium low-density steel, while alleviating its harmful effect on ductility by controlling its morphology and dispersion. The specific tensile strength and ductility of the developed steel improve on those of the lightest and strongest metallic materials known, titanium alloys. We found that alloying of nickel catalyses the precipitation of nanometre-sized B2 particles in the face-centred cubic matrix of high-aluminium low-density steel during heat treatment of cold-rolled sheet steel. Our results demonstrate how intermetallic compounds can be harnessed in the alloy design of lightweight steels for structural applications and others.


HDAC1 is required for GATA-1 transcription activity, global chromatin occupancy and hematopoiesis.
The activity of hematopoietic factor GATA-1 is modulated through p300/CBP-mediated acetylation and FOG-1 mediated indirect interaction with HDAC1/2 containing NuRD complex. Although GATA-1 acetylation is implicated in GATA-1 activation, the role of deacetylation is not studied. Here, we found that the FOG-1/NuRD does not deacetylate GATA-1. However, HDAC1/2 can directly bind and deacetylate GATA-1. Two arginine residues within the GATA-1 linker region mediates direct interaction with HDAC1. The arginine to alanine mutation (2RA) blocks GATA-1 deacetylation and fails to induce erythroid differentiation. Gene expression profiling and ChIP-seq analysis further demonstrate the importance of GATA-1 deacetylation for gene activation and chromatin recruitment. GATA-12RA knock-in (KI) mice suffer mild anemia and thrombocytopenia with accumulation of immature erythrocytes and megakaryocytes in bone marrow and spleen. Single cell RNA-seq analysis of Lin- cKit+ (LK) cells further reveal a profound change in cell subpopulations and signature gene expression patterns in HSC, myeloid progenitors, and erythroid/megakaryocyte clusters in KI mice. Thus, GATA-1 deacetylation and its interaction with HDAC1 modulates GATA-1 chromatin binding and transcriptional activity that control erythroid/megakaryocyte commitment and differentiation.


Surgical correction of residual hip dysplasia in two pediatric age-groups.
The goal of operative treatment of hip dysplasia or subluxation in children is to normalize the hip joint to delay or prevent the premature onset of osteoarthritis. In theory, intervention in early childhood, when the remodeling potential is greater, should provide the best opportunity for the development of a normal joint. To determine the efficacy of early surgical intervention in restoring the normal morphology of the hip, according to radiographic criteria, we reviewed the cases of thirty-six children (fifty hips) with residual dysplasia or subluxation who were managed with either a femoral and/or a pelvic osteotomy when they were between two and eight years old (Group I). The average age at the time of surgery was 3.7 years, and the average duration of follow-up was 4.3 years. We compared these results with those achieved in fourteen patients (eighteen hips) with residual hip dysplasia or subluxation who were treated surgically at an older age, between eight and eighteen years old (Group II). The outcome was assessed with use of clinical as well as multiple radiographic criteria. We believe that a normal relationship between the acetabulum and the femoral head was established when there was an acetabular index of <20 degrees or a Sharp angle of <42 degrees, a center-edge angle of >20 degrees, and an intact Shenton's line. At the time of the latest follow-up, sixteen of the seventeen hips with residual dysplasia that had been treated with pelvic osteotomy alone in Group I and three of four such hips in Group II had a normal relationship between the acetabulum and the femoral head. Normal radiographic findings were noted in fifteen of the seventeen hips with residual subluxation that had been treated with combined femoral and pelvic osteotomies in Group I compared with four of eight such hips in Group II. We found that residual hip dysplasia or subluxation could be more predictably corrected, with normal radiographic results and with less morbidity and fewer complications, in children who were between two and eight years old than in those who were between eight and eighteen years old. Long-term follow-up is required to confirm whether the improved anatomy and function of the hip that resulted from early correction of residual dysplasia or subluxation lasts into adulthood.


Detecting drought regulators using stochastic inference in Bayesian networks.
Drought is a natural hazard that affects crops by inducing water stress. Water stress, induced by drought accounts for more loss in crop yield than all the other causes combined. With the increasing frequency and intensity of droughts worldwide, it is essential to develop drought-resistant crops to ensure food security. In this paper, we model multiple drought signaling pathways in Arabidopsis using Bayesian networks to identify potential regulators of drought-responsive reporter genes. Genetically intervening at these regulators can help develop drought-resistant crops. We create the Bayesian network model from the biological literature and determine its parameters from publicly available data. We conduct inference on this model using a stochastic simulation technique known as likelihood weighting to determine the best regulators of drought-responsive reporter genes. Our analysis reveals that activating MYC2 or inhibiting ATAF1 are the best single node intervention strategies to regulate the drought-responsive reporter genes. Additionally, we observe simultaneously activating MYC2 and inhibiting ATAF1 is a better strategy. The Bayesian network model indicated that MYC2 and ATAF1 are possible regulators of the drought response. Validation experiments showed that ATAF1 negatively regulated the drought response. Thus intervening at ATAF1 has the potential to create drought-resistant crops.


Refractory seizures secondary to radiation-induced focal cortical dysplasia/neuronal gigantism: illustrative case.
Focal cortical dysplasia is a structural cause of drug-resistant epilepsy commonly identified in childhood. In rare cases, radiation-induced injury has led to radiation-induced cortical dysplasia, also known as "focal neuronal gigantism." The authors present a 53-year-old woman with recurrent status epilepticus events after she had radiation therapy and surgery for a left frontal meningioma several years prior. Imaging revealed findings consistent with radiation necrosis and possible recurrence. The patient's status epilepticus events required escalating therapies to manage. Scalp electroencephalography indicated that the seizure's origin was in the left hemisphere. A craniotomy was performed to remove the left frontal lesion, and histopathology was consistent with radiation-induced focal cortical dysplasia/neuronal gigantism. The patient's seizures ceased following the surgery, and she remains on maintenance antiseizure medications. Radiation-induced focal cortical dysplasia/neuronal gigantism is an incredibly rare complication of therapy. However, it warrants consideration in the context of radiation necrosis and intractable epilepsy.


Twelve tips for teaching implicit bias recognition and management.
Implicit biases describe mental associations that affect our actions in an unconscious manner. We can hold certain implicit biases regarding members of certain social groups. Such biases can perpetuate health disparities by widening inequity and decreasing trust in both healthcare and medical education. Despite the widespread discourse about bias in medical education, teaching and learning about the topic should be informed by empirical research and best practice. In this paper, the authors provide a series of twelve tips for teaching implicit bias recognition and management in medical education. Each tip provides a specific and practical strategy that is theoretically and empirically developed through research and evaluation. Ultimately, these twelve tips can assist educators to incorporate implicit bias instruction across the continuum of medical education to improve inequity and advance justice.


Genome-wide association study of recurrent early-onset major depressive disorder.
A genome-wide association study was carried out in 1020 case subjects with recurrent early-onset major depressive disorder (MDD) (onset before age 31) and 1636 control subjects screened to exclude lifetime MDD. Subjects were genotyped with the Affymetrix 6.0 platform. After extensive quality control procedures, 671 424 autosomal single nucleotide polymorphisms (SNPs) and 25 068 X chromosome SNPs with minor allele frequency greater than 1% were available for analysis. An additional 1 892 186 HapMap II SNPs were analyzed based on imputed genotypic data. Single-SNP logistic regression trend tests were computed, with correction for ancestry-informative principal component scores. No genome-wide significant evidence for association was observed, assuming that nominal P<5 × 10(-8) approximates a 5% genome-wide significance threshold. The strongest evidence for association was observed on chromosome 18q22.1 (rs17077540, P=1.83 × 10(-7)) in a region that has produced some evidence for linkage to bipolar-I or -II disorder in several studies, within an mRNA detected in human brain tissue (BC053410) and approximately 75 kb upstream of DSEL. Comparing these results with those of a meta-analysis of three MDD GWAS data sets reported in a companion article, we note that among the strongest signals observed in the GenRED sample, the meta-analysis provided the greatest support (although not at a genome-wide significant level) for association of MDD to SNPs within SP4, a brain-specific transcription factor. Larger samples will be required to confirm the hypothesis of association between MDD (and particularly the recurrent early-onset subtype) and common SNPs.


How curvature-generating proteins build scaffolds on membrane nanotubes.
Bin/Amphiphysin/Rvs (BAR) domain proteins control the curvature of lipid membranes in endocytosis, trafficking, cell motility, the formation of complex subcellular structures, and many other cellular phenomena. They form 3D assemblies that act as molecular scaffolds to reshape the membrane and alter its mechanical properties. It is unknown, however, how a protein scaffold forms and how BAR domains interact in these assemblies at protein densities relevant for a cell. In this work, we use various experimental, theoretical, and simulation approaches to explore how BAR proteins organize to form a scaffold on a membrane nanotube. By combining quantitative microscopy with analytical modeling, we demonstrate that a highly curving BAR protein endophilin nucleates its scaffolds at the ends of a membrane tube, contrary to a weaker curving protein centaurin, which binds evenly along the tube's length. Our work implies that the nature of local protein-membrane interactions can affect the specific localization of proteins on membrane-remodeling sites. Furthermore, we show that amphipathic helices are dispensable in forming protein scaffolds. Finally, we explore a possible molecular structure of a BAR-domain scaffold using coarse-grained molecular dynamics simulations. Together with fluorescence microscopy, the simulations show that proteins need only to cover 30-40% of a tube's surface to form a rigid assembly. Our work provides mechanical and structural insights into the way BAR proteins may sculpt the membrane as a high-order cooperative assembly in important biological processes.


New 4',5'-methylenedioxyflavone derivatives from the whole plant of sarcandra glabra.
Two new natural products named 5,7-dihydroxy-3,3',6,8-tetramethoxy-4',5'-methylenedioxyflavone (1) and 3,3',5,7-tetramethoxy-4',5'-methylenedioxyflavone (2), along with thirteen known compounds, β-sitosterol (3), desmethoxyyangonin (4), hexadecane (5), 3,9-bis(2,4-di-tert-butylphenoxy)-2,4,8,10-tetraoxa-3,9-diphosphaspiro [5.5] undecane 3,9-dioxide (6), 2'6'-dihydroxy-4'-methoxydihydrochalcone (7), cardamonin (8), 3,3',5,6,7,8-hexamethoxy-4',5'-methylenedioxyflavone (9), isofraxidin (10), aniba dimer A (11), 3,3',4',5,5',8-hexamethoxy-6,7-methylenedioxyflavone (12), quercetin (13), quercitrin (14) and isoquercitrin (15) were isolated from Sarcandra glabra (Thunb.) Nakai by various chromatographic methods. Compounds 1, 2, 4, 6, 11, and 12 were isolated from S. glabra for the first time. Their chemical structures were identified through the analysis of NMR and HR-MS spectra. The anti-inflammatory and cytotoxic activities of compounds 1-15 were evaluated in cell assays. The results indicated that compounds 1, 7, 8, 10, 14, and 15 significantly inhibited the NO production in LPS-induced RAW 264.7 murine macrophage cells. Moreover, compounds 1, 3, 4, 7, 8, 9, 10 and 12 exhibited a cytotoxic effect on the human HepG2 cell line.


Some hormone, cytokine and chemokine levels that change across lifespan vary by cognitive status in male Fischer 344 rats.
We trained and tested young (6-8months; n=13), middle-aged (12-14months; n=41), and aged (22-24months; n=24) male Fischer 344 rats in a rapid acquisition water maze task and then quantified 27 stress hormones, cytokines and chemokines in their serum, hippocampi and frontal cortices using bead assay kits and xMAP technology. Middle-aged and aged rats learned the location of the hidden platform over training trials more slowly than their young counterparts. After training, young rats outperformed middle-aged and aged rats on both immediate and 24h retention probe trials and about half of the middle-aged and aged (aging) rats exhibited impaired performances when tested on the retention probe trial 24h later. The concentrations of many serum, hippocampal and cortical analytes changed with age often in networks that may represent age-sensitive signaling pathways and the concentrations of some of these analytes correlated with water maze learning and/or memory scores. Serum GRO/KC and RANTES levels, hippocampal GM-CSF levels and cortical IL-9 and RANTES levels were significantly higher in rats categorized as memory-impaired versus elite agers based upon their 24h probe trial performances. Our data add to the emerging picture of how age-related changes in immune and neuroimmune system signaling impacts cognition.


Deflection of spacecraft trajectories as a new test of general relativity.
We derive a simple formula which gives the general relativistic deflection of a spacecraft, idealized as a point mass, for all values of the asymptotic speed V(infinity) (0< or =V(infinity)< or =1). Using this formula we suggest a new test of general relativity (GR) which can be carried out during a proposed interstellar mission that involves a close pass of the Sun. We show that, with foreseeable improvements in spacecraft tracking sensitivity, the deflection of a spacecraft's trajectory in the gravitational field of the Sun could provide a new test of GR.


[125I]fibrin deposition occurs at both early and late intervals of IgE-dependent or contact sensitivity reactions elicited in mouse skin. Mast cell-dependent augmentation of fibrin deposition at early intervals in combined IgE-dependent and contact sensitivity reactions.
When elicited in the skin of mice, either IgE-dependent immediate hypersensitivity reactions or T cell-dependent contact sensitivity (CS) reactions result in local extravasation of [125I]fibrinogen and deposition of [125I]fibrin. However, these two types of reaction differ in kinetics and in requirement for IgE, mast cells, or T cells. In the present study, we investigated the kinetics and magnitude of [125I]fibrin deposition in combined IgE-dependent and CS reactions elicited simultaneously at the same site and compared the results with those obtained when the two reactions were elicited at separate sites. We found that [125I]fibrin deposition in pure IgE-dependent reactions was greater at 2 or 6 h after challenge than at 24 h, but that significant fibrin deposition persisted at those sites 24 h after challenge. In CS reactions, [125I]fibrin deposition was detected as early as 2 h after challenge, indicating that fibrin deposition accompanies the "early component" of CS detected by Van Loveren et al. with the use of measurements of tissue swelling. But much more [125I]fibrin deposition was present in CS reactions at 24 h than at 2 or 6 h after Ag challenge. When IgE-dependent and CS reactions were elicited at the same site, [125I]fibrin deposition at early intervals (2 to 6 h) after challenge was increased three- to 25-fold compared with that seen in isolated CS reactions, but at 24 h the results in the combined reactions were virtually identical to those in CS responses. Studies in genetically mast cell-deficient and congenic normal mice indicated that mast cells were required for expression of the IgE-dependent augmentation of [125I]fibrin deposition observed at early intervals in combined IgE-dependent and CS reactions, but not for the [125I]fibrin deposition associated with "pure" CS reactions. These findings indicate that the net effect of IgE-dependent mast cell activation on CS responses is to increase the fibrin deposition associated with these responses, but this effect is appreciated only at early intervals after elicitation of the reaction.


Determinants of CRP level in statin-treated patients.
All factors of the metabolic syndrome (MetS) are reported to be associated with elevated C-reactive protein (CRP) levels. As CRP levels have been found to decrease as a result of statin treatment, the present study was intended to explore the relationship between CRP and the MetS in statin treated patients. In this study, the relationship between the components of the MetS and CRP level were analysed and factors determining CRP were identified in patients with longstanding intensive lipid lowering therapy with known cardiovascular disease. In this population CRP levels are still associated with the MetS, with waist circumference, fasting glucose level and smoking being the most important determinants of CRP levels. CRP levels are still associated with the MetS in patients treated with intensive lipid lowering therapy.


Adherence to recommendations of inpatient geriatric consultation teams: a multicenter observational study.
Inpatient geriatric consultation teams (IGCTs) provide recommendations for the care of older patients hospitalized on non-geriatric wards based on comprehensive geriatric assessment. The lack of adherence to their recommendations hinders the potential impact of IGCTs. We evaluated the adherence to IGCT recommendations and determined which team and recommendation characteristics are related to higher adherence rates. Multicenter observational study in older adults aged ≥ 75 years admitted to an acute non-geriatric ward. Demographic and adherence data were collected for 30 consecutive patients. A cross-sectional survey mapped team and organizational characteristics of the participating IGCTs. Analyses were conducted in 278 patients (51.4% male, mean age 82.5 years, and median length of stay 10 days). There was a median number of 3 recommendations (range 1-13) per patient. The overall adherence rate was 69.7%. Recommendations related to 'social status' (82.4%) and 'functional status/mobility' (73.3%) were best adhered to. Recommendations related to 'medication' (53.2%) and 'nutritional status' (59.1%) were least adhered to. Adherence rates increased if recommendations were given to allied health professionals (OR = 6.37, 95% CI = 1.15-35.35) or by more experienced IGCTs (OR = 1.34, 95% CI = 1.04-1.72) and decreased when more recommendations were given (OR = 0.51, 95% CI = 0.33-0.80). Adherence rate to IGCT recommendations increased if given to allied health professionals or by more experienced IGCTs and when fewer recommendations were given. Study replication in an international multicenter study with a larger number of centers and evaluating the quality of the recommendations is suggested.


Cortical Thickness and Surface Area Networks in Healthy Aging, Alzheimer's Disease and Behavioral Variant Fronto-Temporal Dementia.
Models of the human brain as a complex network of inter-connected sub-units are important in helping to understand the structural basis of the clinical features of neurodegenerative disorders. The aim of this study was to characterize in a systematic manner the differences in the structural correlation networks in cortical thickness (CT) and surface area (SA) in Alzheimer's disease (AD) and behavioral variant Fronto-Temporal Dementia (bvFTD). We have used the baseline magnetic resonance imaging (MRI) data available from a large population of patients from three clinical trials in mild to moderate AD and mild bvFTD and compared this to a well-characterized healthy aging cohort. The study population comprised 202 healthy elderly subjects, 213 with bvFTD and 213 with AD. We report that both CT and SA network architecture can be described in terms of highly correlated networks whose positive and inverse links map onto the intrinsic modular organization of the four cortical lobes. The topology of the disturbance in structural network is different in the two disease conditions, and both are different from normal aging. The changes from normal are global in character and are not restricted to fronto-temporal and temporo-parietal lobes, respectively, in bvFTD and AD, and indicate an increase in both global correlational strength and in particular nonhomologous inter-lobar connectivity defined by inverse correlations. These inverse correlations appear to be adaptive in character, reflecting coordinated increases in CT and SA that may compensate for corresponding impairment in functionally linked nodes. The effects were more pronounced in the cortical thickness atrophy network in bvFTD and in the surface area network in AD. Although lobar modularity is preserved in the context of neurodegenerative disease, the hub-like organization of networks differs both from normal and between the two forms of dementia. This implies that hubs may be secondary features of the connectivity adaptation to neurodegeneration and may not be an intrinsic property of the brain. However, analysis of the topological differences in hub-like organization CT and SA networks, and their underlying positive and negative correlations, may provide a basis for assisting in the differential diagnosis of bvFTD and AD.


Injected Human Muscle Precursor Cells Overexpressing PGC-1α Enhance Functional Muscle Regeneration after Trauma.
While many groups demonstrated new muscle tissue formation after muscle precursor cell (MPC) injection, the capacity of these cells to heal muscle damage, for example, sphincter in stress urinary incontinence, in long-term is still limited. Therefore, the first goal of our project was to optimize the functional regenerative potential of hMPC by genetic modification to overexpress human peroxisome proliferator-activated receptor gamma coactivator 1-alpha (hPGC-1α), key regulator of exercise-mediated adaptation. Moreover, we aimed at establishing a feasible methodology for noninvasive PET visualization of implanted cells and their microenvironment in muscle crush injury model. PGC-1α-bioengineered muscles showed enhanced marker expression for myogenesis (α-actinin, MyHC, and Desmin), vascularization (VEGF), neuronal (ACHE), and mitochondrial (COXIV) activity. Consistently, use of hPGC-1α_hMPCs produced significantly increased contractile force one to three weeks postinjury. PET imaging showed distinct differences in radiotracer signals ([18F]Fallypride and [11C]Raclopride (both targeting dopamine 2 receptors (D2R)) and [64Cu]NODAGA-RGD (targeting neovascularization)) between GFP_hMPCs and hD2R_hPGC-1α_hMPCs. After muscle harvesting, inflammation levels were in parallel to radiotracer uptake amount, with significantly lower uptake in hPGC-1α overexpressing samples. In summary, we facilitated early functional muscle tissue regeneration, introducing a novel approach to improve skeletal muscle regeneration. Besides successful tracking of hMPCs in muscle crush injuries, we showed that in high-inflammation areas, the specificity of radioligands might be significantly reduced, addressing a possible bottleneck of neovascularization PET imaging.


Torsional stiffness after subtalar arthrodesis using second generation headless compression screws: Biomechanical comparison of 2-screw and 3-screw fixation.
Subtalar joint arthrodesis is a common operative treatment for symptomatic subtalar arthrosis. Because excessive relative motion between the talus and calcaneus can delay or prohibit fusion, fixation should be optimized, particularly in patients at risk for subtalar arthrodesis nonunion. Tapered, fully-threaded, variable pitch screws are gaining popularity for this application, but the mechanical properties of joints fixed with these screws have not been characterized completely. We quantified the torsion resistance of 2-screw and 3-screw subtalar joint fixation using this type of screw. Ten pairs of cadaveric subtalar joints were prepared for arthrodesis and fixed using Acutrak 2-7.5 screws. One specimen from each pair was fixed with two diverging posterior screws, and the contralateral joint was fixed using two posterior screws and a third screw directed through the anterior calcaneus into the talar neck. Internal and external torsional loads were applied and joint rotation and torsional stiffness were measured at two torque levels. Internal rotation was significantly less in specimens fixed with three screws. No difference was detectable between 2-screw and 3-screw fixation in external rotation or torsional stiffness in either rotation direction. Both 2-screw and 3-screw fixation exhibited torsion resistance surpassing that reported previously for subtalar joints fixed with two diverging conventional lag screws. Performance of the tapered, fully threaded, variable pitch screws exceeded that of conventional lag screws regardless of whether two or three screws were used. Additional resistance to internal rotation afforded by a third screw placed anteriorly may offer some advantage in patients at risk for nonunion.


Short-term outcomes for super-super obese (BMI > or =60 kg/m2) patients undergoing weight loss surgery at a high-volume bariatric surgery center: laparoscopic adjustable gastric banding, laparoscopic gastric bypass, and open tubular gastric bypass.
We previously reported significantly longer operating room times and a trend toward increased complications and mortality in the super-super obese (body mass index [BMI] > or =60 kg/m(2)) early in our experience with laparoscopic Roux-en-Y gastric bypass. The goal of this study was to re-examine the short-term outcomes for super-super obese patients undergoing weight loss surgery at our high-volume bariatric surgery center well beyond our learning curve. The records for all patients who had undergone weight loss surgery at Hackensack University Medical Center from 2002 to June 2006 were harvested from the hospital's electronic medical database. This population was analyzed as 2 groups (those with a BMI <60 kg/m(2) and those with a BMI > or =60 kg/m(2)), as well as by type of operation. Step-wise and univariate logistic regression analyses assessed the effect of BMI on the outcome variables, including mortality, length of surgery, length of hospital stay, and disposition at discharge. A total of 3692 patients were studied. Of these patients, 3401 had a BMI <60 kg/m(2) and 291 had a BMI > or =60 kg/m(2). Of the 291 super-super obese patients, 130 underwent vertical banded gastroplasty-Roux-en-Y gastric bypass, 116 laparoscopic Roux-en-Y gastric bypass, and 45 laparoscopic adjustable gastric banding. The proportion of male patients, black patients, and patients with sleep apnea was increased in the BMI > or =60 kg/m(2) group. The number of co-morbid diseases per patient correlated with age but not BMI. The BMI > or =60 kg/m(2) group required a significantly longer total operating room time (136 versus 120 min). Hospital length of stay was significantly longer only in the laparoscopic Roux-en-Y gastric bypass patients (3 d for the BMI > or =60 kg/m(2) group versus 2 d for the BMI <60 kg/m(2) group). A significantly greater percentage of patients in the super-super obese group were discharged to chronic care facilities. The overall in-hospital mortality rate was 0.15% (5 of 3692) but did not significantly differ between the 2 groups: BMI <60 kg/m(2), rate of 0.12% (4 of 3401 patients), and BMI > or =60 kg/m(2), rate of 0.34% (1 of 291 patients). The type of operation did not significantly affect the disposition at discharge or in-hospital mortality. Super-super obese patients required longer total operating room times, a longer hospital length of stay, and were more likely to be discharged to chronic care facilities than were patients with a BMI <60 kg/m(2); however, the in-hospital mortality was similar for both groups.


Rethinking the approach to viability monitoring in seed genebanks.
Seed viability monitoring, usually through a germination test, is a key aspect of genebank management; a low viability result triggers the regeneration of an accession in order to ensure that the genetic diversity of the accession is conserved and available for distribution. However, regular viability monitoring of large collections is costly in terms of seeds, labour and other resources. Genebanks differ in how they conduct their viability monitoring and how they collect, manage and store the data that are generated. In this article, we propose alternatives to the current norm of conducting an initial germination test soon after arrival at the genebank and then testing after regular, set storage intervals, as recommended in the Food and Agriculture Organization's Genebank Standards for Plant Genetic Resources for Food and Agriculture. We use real data from the International Rice Genebank (held at the International Rice Research Institute) to illustrate some of the issues regarding the accuracy and reliability of germination test results, in particular when they are used to predict the longevity of a seed lot in storage and to set viability monitoring intervals. We suggest the use of seed storage experiments on samples of seeds to identify which seed lots from a particular crop season to test first. We also give advice on the use of sequential testing schemes potentially to reduce the number of seeds used for viability testing; the use of tolerance tables to identify unlikely results when samples are subdivided into replicates; and what data to include in a genebank management database to improve the management of seed collections.


A circular plasmid from the yeast Torulaspora delbrueckii.
A new member of the 2-micron family of plasmids, named pTD1, was found in the yeast Torulaspora delbrueckii, a widespread yeast associated with food. Nucleotide sequences revealed the presence of a pair of inverted repeats and three open reading frames, one of which is a homologue of the FLP recombinase gene of 2-micron plasmid. An ARS region was identified, by replication in Saccharomyces cerevisiae and T. delbrueckii, near one of the inverted repeats. By the use of pTD1 derivatives and auxotrophic mutant hosts an efficient host-vector system was established for T. delbrueckii. So far, the 2-micron family of plasmids is restricted to four closely related genera (Q6 group): Saccharomyces, Zygosaccharomyces, Kluyveromyces, and Torulaspora. After a survey of 2500 strains belonging to about 500 species (80 genera) of yeast, no circular plasmids were found in other genera.


A Structural Equation Modeling on Reproductive Health Promoting Behavior of Unmarried Women: Based on the Theory of Planned Behavior.
The purpose of this study was to construct and test a structural equation modeling on the reproductive health behavior of single women with sexual experiences. This study employed Ajzen's Theory of Planned Behavior (TPB). The data were collected after receipt of consent from 250 single women with sexual experiences, and analyzed using SPSS 18.0 and AMOS 18.0. Model fit indices for the hypothetical model were suitable for the recommended level: x²=362.407, RMR=0.065, RMSEA=0.070, GFI=0.867. TLI=0.927, CFI=0.938, IFI=0.939, and x²/dF=2.237. Intention showed direct effect with the biggest effect being on reproductive health behavior. Attitude, subjective norm and perceived behavioral control were found to have a direct effect on intention. Among them, perceived behavioral control revealed the largest influence. This study suggests that the TPB is a suitable model in explaining the reproductive health behavior of single women with sexual experience. Strategic plans for educational and intervention programs should be aimed to encourage single women to engage in reproductive health behavior.


Dementia subtypes, cognitive decline and survival among older adults attending a memory clinic in Cape Town, South Africa: a retrospective study.
There are no published longitudinal studies from Africa of people with dementia seen in memory clinics. The aim of this study was to determine the proportions of the different dementia subtypes, rates of cognitive decline, and predictors of survival in patients diagnosed with dementia and seen in a memory clinic. Data were collected retrospectively from clinic records of patients aged ≥ 60 seen in the memory clinic at Groote Schuur Hospital, Cape Town, South Africa over a 10-year period. Diagnostic and Statistical Manual of Mental Disorders (DSM-5) criteria were used to identify patients with Major Neurocognitive Disorders (dementia). Additional diagnostic criteria were used to determine the specific subtypes of dementia. Linear regression analysis was used to determine crude rates of cognitive decline, expressed as mini-mental state examination (MMSE) points lost per year. Changes in MMSE scores were derived using mixed effects modelling to curvilinear models of cognitive change, with time as the dependent variable. Multivariable cox survival analysis was used to determine factors at baseline that predicted mortality. Of the 165 patients who met inclusion criteria, 117(70.9%) had Major Neurocognitive Disorder due to Alzheimer's disease (AD), 24(14.6%) Vascular Neurocognitive Disorder (VND), 6(3.6%) Dementia with Lewy Bodies (DLB), 5(3%) Parkinson disease-associated dementia (PDD), 3(1.8%) fronto-temporal dementia, 4(2.4%) mixed dementia and 6(3.6%) other types of dementia. The average annual decline in MMSE points was 2.2(DLB/PDD), 2.1(AD) and 1.3(VND). Cognitive scores at baseline were significantly lower in patients with 8 compared to 13 years of education and in those with VND compared with AD. Factors associated with shorter survival included age at onset greater than 65 (HR = 1.82, 95% C.I. 1.11, 2.99, p = 0.017), lower baseline MMSE (HR = 1.05, 95% C.I. 1.01, 1.10, p = 0.029), Charlson's comorbidity scores of 3 to 4 (HR = 1.88, 95% C.I. 1.14, 3.10, p = 0.014), scores of 5 or more (HR = 1.97, 95% C.I. 1.16, 3.34, p = 0.012) and DLB/PDD (HR = 3.07, 95% C.I. 1.50, 6.29, p = 0.002). Being female (HR = 0.59, 95% C.I.0.36, 0.95, p = 0.029) was associated with longer survival. Knowledge of dementia subtypes, the rate and factors affecting cognitive decline and survival outcomes will help inform decisions about patient selection for potential future therapies and for planning dementia services in resource-poor settings.


A cytosolic Ezh1 isoform modulates a PRC2-Ezh1 epigenetic adaptive response in postmitotic cells.
The evolution of chromatin-based epigenetic cell memory may be driven not only by the necessity for cells to stably maintain transcription programs, but also by the need to recognize signals and allow plastic responses to environmental stimuli. The mechanistic role of the epigenome in adult postmitotic tissues, however, remains largely unknown. In vertebrates, two variants of the Polycomb repressive complex (PRC2-Ezh2 and PRC2-Ezh1) control gene silencing via methylation of histone H3 on Lys27 (H3K27me). Here we describe a reversible mechanism that involves a novel isoform of Ezh1 (Ezh1β). Ezh1β lacks the catalytic SET domain and acts in the cytoplasm of skeletal muscle cells to control nuclear PRC2-Ezh1 activity in response to atrophic oxidative stress, by regulating Eed assembly with Suz12 and Ezh1α (the canonical isoform) at their target genes. We report a novel PRC2-Ezh1 function that utilizes Ezh1β as an adaptive stress sensor in the cytoplasm, thus allowing postmitotic cells to maintain tissue integrity in response to environmental changes.


Medical staff bylaws: regulations or contract?
St. John's Hospital Medical Staff v. St. John Regional Medical Center is the point of departure in an exploration of the issue of whether medical staff bylaws constitute a contract or are merely important regulations. Also discussed is the practical application of bylaws in day-to-day hospital operations.


Impact of high-risk prenatal screening results for 22q11.2 deletion syndrome on obstetric and neonatal management: Secondary analysis from the SMART study.
One goal of prenatal genetic screening is to optimize perinatal care and improve infant outcomes. We sought to determine whether high-risk cfDNA screening for 22q11.2 deletion syndrome (22q11.2DS) affected prenatal or neonatal management. This was a secondary analysis from the SMART study. Patients with high-risk cfDNA results for 22q11.2DS were compared with the low-risk cohort for pregnancy characteristics and obstetrical management. To assess differences in neonatal care, we compared high-risk neonates without prenatal genetic confirmation with a 1:1 matched low-risk cohort. Of 18,020 eligible participants enrolled between 2015 and 2019, 38 (0.21%) were high-risk and 17,982 (99.79%) were low-risk for 22q11.2DS by cfDNA screening. High-risk participants had more prenatal diagnostic testing (55.3%; 21/38 vs. 2.0%; 352/17,982, p < 0.001) and fetal echocardiography (76.9%; 10/13 vs. 19.6%; 10/51, p < 0.001). High-risk newborns without prenatal diagnostic testing had higher rates of neonatal genetic testing (46.2%; 6/13 vs. 0%; 0/51, P < 0.001), echocardiography (30.8%; 4/13 vs. 4.0%; 2/50, p = 0.013), evaluation of calcium levels (46.2%; 6/13 vs. 4.1%; 2/49, P < 0.001) and lymphocyte count (53.8%; 7/13 vs. 15.7%; 8/51, p = 0.008). High-risk screening results for 22q11.2DS were associated with higher rates of prenatal and neonatal diagnostic genetic testing and other 22q11.2DS-specific evaluations. However, these interventions were not universally performed, and >50% of high-risk infants were discharged without genetic testing, representing possible missed opportunities to improve outcomes for affected individuals.


Whole organisms and purified cell walls compared as immunosorbents for the detection of IgE antibodies to Staphylococcus aureus.
We have developed an immunoradiometric assay for IgE antibodies to Staphylococcus aureus (Staph IgE-Ab) which uses purified cell walls (PCW) from the Wood 46 strain of S. aureus as an immunosorbent. We compared Wood 46 PCW and whole organisms (WO) as immunosorbents for Staph IgE-Ab by performing tests on sera from patients with atopic dermatitis (AD) or the hyperimmunoglobulin E syndrome (hyper IgE syndrome). Sera with Staph IgE-Ab demonstrated dose-dependent binding to PCW and WO, but the ratio of specific to non-specific binding was much greater with PCW. Mean non-specific binding to WO was greater than to PCW, 5% versus 2%; and non-specific binding to WO varied directly with the serum concentration of IgE. Results of tests on patients' sera indicated that PCW are required in screening assays for Staph IgE-Ab to avoid false positive results caused by high levels of non-specific binding to WO.


The Role of P2X7 Purinoceptors in the Pathogenesis and Treatment of Muscular Dystrophies.
Muscular dystrophies are inherited neuromuscular diseases, resulting in progressive disability and often affecting life expectancy. The most severe, common types are Duchenne muscular dystrophy (DMD) and Limb-girdle sarcoglycanopathy, which cause advancing muscle weakness and wasting. These diseases share a common pathomechanism where, due to the loss of the anchoring dystrophin (DMD, dystrophinopathy) or due to mutations in sarcoglycan-encoding genes (LGMDR3 to LGMDR6), the α-sarcoglycan ecto-ATPase activity is lost. This disturbs important purinergic signaling: An acute muscle injury causes the release of large quantities of ATP, which acts as a damage-associated molecular pattern (DAMP). DAMPs trigger inflammation that clears dead tissues and initiates regeneration that eventually restores normal muscle function. However, in DMD and LGMD, the loss of ecto-ATPase activity, that normally curtails this extracellular ATP (eATP)-evoked stimulation, causes exceedingly high eATP levels. Thus, in dystrophic muscles, the acute inflammation becomes chronic and damaging. The very high eATP over-activates P2X7 purinoceptors, not only maintaining the inflammation but also tuning the potentially compensatory P2X7 up-regulation in dystrophic muscle cells into a cell-damaging mechanism exacerbating the pathology. Thus, the P2X7 receptor in dystrophic muscles is a specific therapeutic target. Accordingly, the P2X7 blockade alleviated dystrophic damage in mouse models of dystrophinopathy and sarcoglycanopathy. Therefore, the existing P2X7 blockers should be considered for the treatment of these highly debilitating diseases. This review aims to present the current understanding of the eATP-P2X7 purinoceptor axis in the pathogenesis and treatment of muscular dystrophies.


Clinical Referral Laboratories in Rwanda.
We investigated the quality system performance in Rwandan referral laboratories to determine their progress toward accreditation. We conducted audits across five laboratories in 2017, using the Stepwise Laboratory Quality Improvement Process Towards Accreditation checklist. Laboratories were scored based on the World Health Organization grading scale (0-5 stars scale) and compared with earlier audits. Between 2012 and 2017, only one laboratory progressed (from four to five stars). Four of the five laboratories decreased to one (three laboratories) and zero (one laboratory) stars from four and three stars. Management reviews, evaluation, audits, documents, records, and identification of nonconformities showed a low performance. Four of five laboratories are not moving toward accreditation. However, this target is still achievable by energizing responsibilities of stakeholders and monitoring and evaluation. This would be possible because of the ability that laboratories showed in earlier audits, coupled with existing health policy that enables sustainable quality health care in Rwanda.


Reduced expression of synapsin II in a chronic phencyclidine preclinical rat model of schizophrenia.
Schizophrenia is a mental disorder characterized by positive symptoms, negative symptoms, and cognitive dysfunction. Phencyclidine (PCP)-a N-methyl-D-aspartate (NMDA) receptor antagonist-induces symptoms indistinguishable from those of schizophrenia. A reduction of the phosphoprotein synapsin II has also been implicated in schizophrenia and has a well-known role in the maintenance of the presynaptic reserve pool and vesicle mobilization. This study assessed the behavioral and biochemical outcomes of chronic NMDA receptor antagonism in rodents and its implications for the pathophysiology of schizophrenia. Sprague Dawley rats received saline or chronic PCP (5 mg/kg/day) for 14 days via surgically implanted Alzet® osmotic mini-pumps. Following the treatment period, rats were tested with a series of behavioral paradigms, including locomotor activity, social interaction, and sensorimotor gating. Following behavioral assessment, the medial prefrontal cortex (mPFC) of all rats was isolated for synapsin II protein analysis. Chronic PCP treatment yielded a hyper-locomotive state (p = 0.0256), reduced social interaction (p = 0.0005), and reduced pre-pulse inhibition (p < 0.0001) in comparison to saline-treated controls. Synapsin IIa (p < 0.0001) and IIb (p < 0.0071) levels in the mPFC of chronically treated PCP rats were reduced in comparison to the saline group. Study results confirm that rats subject to chronic PCP treatment display behavioral phenotypes similar to established preclinical animal models of schizophrenia. Reduction of synapsin II expression in this context implicates the role of this protein in the pathophysiology of schizophrenia and sheds light on the longer-term consequences of NMDA receptor antagonism facilitated by chronic PCP treatment.


Sustainable and practical degradation of intact chicken feathers by cultivating a newly isolated thermophilic Meiothermus ruber H328.
The sustainable and practical degradation of intact chicken feathers by a newly isolated thermophilic bacterium Meiothermus ruber H328 was presented with extensive data. Aerobic cultivation with moderately thermophilic strain H328 at 55 degrees C for 6 days led to the apparently complete decay of the truly intact feathers and provided 1.89 mmol free amino acids and 7.32 mmol acid-hydrolyzed amino acids from 50 ml of culture containing 3% (w/v) intact chicken feathers. The amino acid components in the soluble fraction of the culture conspicuously agreed with those calculated from the intact feathers. This demonstrated that more than 55% of total keratin proteins were solubilized from the intact chicken feathers into the culture in the forms of free amino acid and/or soluble oligopeptide, and most of them are directly derived from the intact feathers by proteolytic digestion. Feather degradation by strain H328 surpasses that by any other microorganisms with regard to degradation efficiency, absence of requirement for pretreatment of the feathers, and product fidelity in the amino acid component. Furthermore, the culture containing the degradative products from the intact feathers was subjected to matrix-assisted laser desorption ionization mass spectrometry-time-of-flight analysis, and it was revealed that the molecular masses of the solubilized products, oligopeptides, were less than 1,000. This result allows us to investigate the bioactivities of oligopeptides derived from the degradation of chicken feathers by cultivation with strain H328 as well as the production of amino acids for feedstuffs.


Challenges in Preparation of Cumulative Antibiogram Reports for Community Hospitals.
Knowledge of local antimicrobial resistance is critical for management of infectious diseases. Community hospitals' compliance with Clinical and Laboratory Standards Institute (CLSI) guidance for creation of cumulative antibiograms is uncertain. This descriptive cohort study of antibiogram reporting practices included community hospitals enrolled in the Duke Infection Control Outreach Network. Cumulative antibiograms from 2012 were reviewed for criteria on reporting practices and compliance with CLSI guidelines. Microbiology personnel were sent a voluntary, electronic survey on antibiogram preparation practices. Data were compiled using descriptive statistics. Thirty-two of 37 (86%) hospitals provided antibiograms; 26 of 37 (70%) also provided survey responses. Twelve (38%) antibiograms specified methods used for compiling data and exclusion of duplicates. Eight (25%) reported only species with >30 isolates. Of the 24 that did not follow the 30-isolate rule, 3 (13%) included footnotes to indicate impaired statistical validity. Twenty (63%) reported at least 1 pathogen-drug combination not recommended for primary or supplemental testing per CLSI. Thirteen (41%) separately reported methicillin-resistant and -susceptible Staphylococcus aureus. Complete compliance with CLSI guidelines was observed in only 3 (9%) antibiograms. Survey respondents' self-assessment of full or partial compliance with CLSI guidelines was 50% and 15%, respectively; 33% reported uncertainty with CLSI guidelines. Full adherence to CLSI guidelines for hospital antibiograms was uncommon. Uncertainty about CLSI guidelines was common. Alternate strategies, such as regional antibiograms using pooled data and educational outreach efforts, are needed to provide reliable and appropriate susceptibility estimates for community hospitals.


LncRNA GUSBP5-AS promotes EPC migration and angiogenesis and deep vein thrombosis resolution by regulating FGF2 and MMP2/9 through the miR-223-3p/FOXO1/Akt pathway.
Long non-coding RNAs (lncRNAs) play an essential role in multitudinous physiological and pathological processes, including vascular disease. We previously showed that lncRNA GUSBP5-AS (enst00000511042) is upregulated in endothelial progenitor cells (EPCs) of deep veni thrombosis (DVT) patients. Here, we investigate the role and mechanism of GUSBP5-AS in EPCs and DVT. Using the DVT model, we found that GUSBP5-AS significantly reduced the thrombus size and weight and enhanced the homing ability of EPC to DVT sites to promote resolution and recanalization of thrombus. GUSBP5-AS promoted cell cycle progression, proliferation, migration and invasion in EPCs, enhanced EPC angiogenesis in vitro and in vivo, and inhibited apoptosis. Strikingly, this study showed that GUSBP5-AS was unbalanced and modulated Forkhead Box Protein O1 (FOXO1) in EPCs in patients with DVT by interacting with miR-223-3p. Mechanistically, GUSBP5-AS functions as a sponge of miR-223-3p, which targets FOXO1. Both GUSBP5-AS knockdown and miR-223-3p overexpression remarkably inhibited angiogenesis, migration and invasion in EPCs. Additionally, our data suggested that GUSBP-AS activated the Akt pathway and enhanced fibroblast growth factor 2 (FGF2), matrix metalloproteinase-2/9 (MMP2/9) and F-actin expression. Taken together, this study indicates that GUSBP5-AS modulates angiogenesis, proliferation and homing ability of EPCs via regulating FGF2 and MMP2/9 expression through the miR-223-3p/FOXO1/Akt pathway, which may provide a new direction for the development of DVT therapeutics.


Postgenomic approaches to using corynebacteria as biocatalysts.
Corynebacterium glutamicum exhibits numerous ideal intrinsic attributes as a factory of primary and secondary metabolites. The versatile capabilities of this organism have long been implemented at the industrial scale to produce an array of amino acids at high yields and conversion rates, thereby enabling the development of an entire industry. The postgenomic era provides a new technological platform not only to further optimize the intrinsic attributes of C. glutamicum whole cells as biocatalysts, but also to dramatically expand the product portfolio that can be manufactured by this organism, from amino acids to commodity chemicals. This review addresses the methods and strain optimization strategies enabled by genomic information and associated techniques. Their implementation has provided important additional incremental improvements to the economics of industry-scale manufacturing in which C. glutamicum and its episomal elements are used as a performing host-vector system.


[Radioisotopic diagnosis of infected anastomotic groin aneurysms after complications with aorto-bifemoral vascular prosthesis].
Between 1990 and 1996 at the Department of Vascular Surgery, Medical Academy in Wrocław 34 patients with groin aneurysms were operated. All patients had aorto-bifemoral graft implantation before. The age range between 41 and 81 years. Among patients there were 4 women and 30 men. The diagnosis of groin aneurysm was based on physical and ultrasound examination. In each case scintigraphy with 99Tc labeled leukocytes was performed. Scintigraphic picture showed graft infection in eight (23.5%) patients (group I). In 26 (76.5%) cases (group II) there was no infection on scintigraphy. In group I all patients were operated-the infected graft was excised and then implantation of straight PTFE or venous by-pass "in situ" was performed. In group II all patient were also operated, but through the groin approach only -in 9 cases reconstruction of the anastomosis between graft and artery was done and in 17 cases PTFE by-pass was performed. In group I the results of the treatment were good in 6 cases; in remaining two patients the amputation of the leg had to be done. In group II the results of the operation was good in 24 cases and 2 patients had amputation of the leg. Scintigraphy with 99Tc labeled leukocytes is beneficial in the diagnosis of infected groin aneurysms after previous vascular reconstruction.


Effects of BDE-209 contaminated sediments on zebrafish development and potential implications to human health.
Polybrominated diphenyl ethers are compounds widely used as flame-retardants, which are of increasing environmental concern due to their persistence, and potential adverse effects. This study had two objectives. First, we assessed if BDE-209 in sediment was bioavailable and bioaccumulated into zebrafish embryos. Secondly, we assessed the potential impact on human and environmental health of bioavailable BDE-209 using human in vitro cell assays and zebrafish embryos. Zebrafish were exposed from 4h to 8days post-fertilization to sediments spiked with 12.5mg/kg of BDE-209. Zebrafish larvae accumulated ten fold more BDE-209 than controls in unspiked sediment after 8days. BDE-209 impacted expression of neurological pathways and altered behavior of larvae, although BDE-209 had no visible affect on thyroid function or motoneuron and neuromast development. Zebrafish data and in silico predictions suggested that BDE-209 would also interact with key human transcription factors and receptors. We therefore tested these predictions using mammalian in vitro assays. BDE-209 activated human aryl hydrocarbon receptor, peroxisome proliferator activating receptors, CF/b-cat, activator protein 1, Oct-MLP, and the estrogen receptor-related alpha (ERRα) receptor in cell-based assays. BDE-209 also inhibited human acetylcholinesterase activity. The observation that BDE-209 can be bioaccumulated from contaminated sediment highlights the need to consider this as a potential environmental exposure route. Once accumulated, our data also show that BDE-209 has the potential to cause impacts on both human and environmental health.


Chaos theory before Lorenz.
We consider the precursors to the discovery of sensitive dependence on initial conditions by Edward Lorenz (1963) in his model of climatic fluid dynamics. This will focus on work in various disciplines that imply either such sensitivity, irregular endogenous dynamic patterns, or fractal nature of an attractor, as is also found in the attractor underlying the model Lorenz studied. Going from ancient hints in Anaxagoras through nineteenth century mathematics and physics, the main areas of such development will be argued to have been in celestial mechanics, oscillators, and economics.


The microsomal dicarboxylyl-CoA synthetase.
Dicarboxylic acids are products of the omega-oxidation of monocarboxylic acids. We demonstrate that in rat liver dicarboxylic acids (C5-C16) can be converted into their CoA esters by a dicarboxylyl-CoA synthetase. During this activation ATP, which cannot be replaced by GTP, is converted into AMP and PPi, both acting as feedback inhibitors of the reaction. Thermolabile at 37 degrees C, and optimally active at pH 6.5, dicarboxylyl-CoA synthetase displays the highest activity on dodecanedioic acid (2 micromol/min per g of liver). Cell-fractionation studies indicate that this enzyme belongs to the hepatic microsomal fraction. Investigations about the fate of dicarboxylyl-CoA esters disclosed the existence of an oxidase, which could be measured by monitoring the production of H2O2. In our assay conditions this H2O2 production is dependent on and closely follows the CoA consumption. It appears that the chain-length specificity of the handling of dicarboxylic acids by this catabolic pathway (activation to acyl-CoA and oxidation with H2O2 production) parallels the pattern of the degradation of exogenous dicarboxylic acids in vivo.