A novel method for medical implant in-body localization.
Wireless communication medical implants are gaining an important role in healthcare systems by controlling and transmitting the vital information of the patients. Recently, Wireless Capsule Endoscopy (WCE) has become a popular method to visualize and diagnose the human gastrointestinal (GI) tract. Estimating the exact location of the capsule when each image is taken is a very critical issue in capsule endoscopy. Most of the common capsule localization methods are based on estimating one or more location-dependent signal parameters like TOA or RSS. However, some unique challenges exist for in-body localization due to the complex nature within the human body. In this paper, we propose a novel one-stage localization method based on spatial sparsity in 3D space. In this method, we directly estimate the location of the capsule (as the emitter) without going through the intermediate stage of TOA or signal strength estimation. We evaluate the performance of the proposed method using Monte Carlo simulation with an RF signal following the allowable power and bandwidth ranges according to the standards. The results show that the proposed method is very effective and accurate even in massive multipath and shadowing conditions.


High throughput protein production for functional proteomics.
A major impact of genome projects on human health will be their contribution to the understanding of protein function. Proteins are the engines of biological systems, nearly all pharmaceuticals act on proteins and increasingly proteins themselves are used therapeutically. As biology enters the post-genomic era, researchers have begun to embrace the exciting opportunity of investigating proteins in high throughput (HT) experiments. The study of proteins includes a vast array of techniques ranging from enzyme catalysis assays to interaction and structural studies. Many of these methods depend on purified proteins. The discovery of thousands of novel protein-coding sequences and the increased availability of large cDNA collections provide the opportunity to investigate protein function in a systematic manner and at an unprecedented scale. This opportunity highlights the need for development of HT methods for protein isolation. This article describes the challenges faced and the approaches taken to develop proteome-scale protein expression systems.


Insurance status and hospital care for myocardial infarction, stroke, and pneumonia.
Despite widely documented variations in health care outcomes by insurance status, few nationally representative studies have examined such disparities in the inpatient setting. To determine whether there are insurance-related differences in hospital care for 3 common medical conditions. Retrospective database analysis of 154,381 adult discharges (age 18-64 years) with a principal diagnosis of acute myocardial infarction (AMI), stroke, or pneumonia from the 2005 Nationwide Inpatient Sample (NIS). For each diagnosis, we compared in-hospital mortality, length of stay (LOS), and cost per hospitalization for Medicaid and uninsured patients with the privately insured. Compared with the privately insured, in-hospital mortality among AMI and stroke patients was significantly higher for the uninsured (adjusted odds ratio [OR] 1.52, 95% confidence interval [CI] [1.24-1.85] for AMI and 1.49 [1.29-1.72] for stroke) and among pneumonia patients was significantly higher for Medicaid recipients (1.21 [1.01-1.45]). Excluding patients who died during hospitalization, LOS was consistently longer for Medicaid recipients for all 3 conditions (adjusted ratio 1.07, 95% CI [1.05-1.09] for AMI, 1.17 [1.14-1.20] for stroke, and 1.04 [1.03-1.06] for pneumonia), although costs were significantly higher for Medicaid recipients for only 2 of the 3 conditions (adjusted ratio 1.06, 95% CI [1.04-1.09] for stroke and 1.05 [1.04-1.07] for pneumonia). In this nationally representative study of working-age Americans hospitalized for 3 common medical conditions, significantly lower in-hospital mortality was noted for privately insured patients compared with the uninsured or Medicaid recipients. Interventions to reduce insurance-related gaps in inpatient quality of care should be investigated.


Nicotine inhibits voltage-dependent sodium channels and sensitizes vanilloid receptors.
Nicotine is an alkaloid that is used by large numbers of people. When taken into the body, it produces a myriad of physiological actions that occur primarily through the activation of neuronal nicotinic acetylcholine receptors (nAChRs). We have explored its ability to modulate TRPV1 receptors and voltage-gated sodium channels. The reason for investigating nicotine's effect on sodium channels is to obtain a better understanding of its anti-nociceptive properties. The reasons for investigating its effects on capsaicin-activated TRPV1 channels are to understand how it may modulate this channel that is involved in pain, inflammation, and gustatory physiology. Whole cell patch-clamp recordings from rat trigeminal ganglion (TG) nociceptors revealed that nicotine exhibited anesthetic properties by decreasing the number of evoked action potentials and by inhibiting tetrodotoxin-resistant sodium currents. This anesthetic property can be produced without the necessity of activating nAChRs. Nicotine also modulates TRPV1 receptors inducing a several-fold increase in capsaicin-activated currents in both TG neurons and in cells with heterologously expressed TRPV1 receptors. This sensitizing effect does not require the activation of nAChRs. Nicotine did not alter the threshold temperature (approximately 41 degrees C) of heat-activated currents in TG neurons that were attributed to arise from the activation of TRPV1 receptors. In this regard, its effect on TRPV1 receptors differs from those of ethanol that has been shown to increase the capsaicin-activated current but decrease the threshold temperature. These studies document several new effects of nicotine on channels involved in nociception and indicate how they may impact physiological processes involving pain and gustation.


Network-Based Approaches to Understand the Roles of miR-200 and Other microRNAs in Cancer.
microRNAs (miRNA) are well suited to the task of regulating gene expression networks, because any given miRNA has the capacity to target dozens, if not hundreds, of genes. The simultaneous targeting of multiple genes within a pathway may enable miRNAs to more strongly regulate the pathway, or to achieve more subtle control through the targeting of distinct subnetworks of genes. Therefore, as our capacity to discover miRNA targets en masse increases, so must our consideration of the complex networks in which these genes participate. We highlight recent studies in which the comprehensive identification of targets has been used to elucidate miRNA-regulated gene networks in cancer, focusing especially upon miRNAs such as members of the miR-200 family that regulate epithelial-mesenchymal transition (EMT), a reversible phenotypic switch whereby epithelial cells take on the more invasive properties of their mesenchymal counterparts. These studies have expanded our understanding of the roles of miRNAs in EMT, which were already known to form important regulatory loops with key transcription factors to regulate the epithelial or mesenchymal properties of cells.


An aborted, prospective, randomized trial of sclerotherapy for prolonged drainage after mastectomy.
Annually, approximately 100 of the 400 postmastectomy patients we studied have persisting serous drainage. Sclerotherapy with the use of tetracycline has been advocated to decrease serous drainage and the formation of seromas. Reports in the literature suggest that the use of tetracycline for treatment has been efficacious and that it is not painful. We devised a prospective, randomized controlled trial to study the effects of tetracycline on patients with prolonged persisting drainage. Six patients in the control group had the drains left in place until the drainage diminished. One of these patients had a seroma develop after the drains were removed. Eight patients were treated with tetracycline. Four of these patients had seromas develop after the drains were removed. Three of the eight patients had severe reactions of pain when the tetracycline was introduced into the drains. Because of the severe pain associated with sclerotherapy treatment and the lack of demonstrable benefit in those treated, we terminated the study. We did not find tetracycline to be of help in treating patients with prolonged drainage after mastectomy and some of those patients had severe pain develop from the treatment.


Evaluation of cerclage wiring in the treatment of subtrochanteric fractures.
Treatment of subtrochanteric fractures is challenging because of their typical displacement pattern. Use of circumferential cerclage wires can be added to intramedullary nailing to facilitate better anatomical reduction. Concerns exist regarding additional soft tissue damage and ischemia of the periosteum. The aim of this study was to assess the effect of cerclage on union and infection rates. The postoperative results of 115 patients over 11 years were retrospectively viewed. Twenty-three patients were treated with cerclage. The primary outcome measure was 'return to theatre for fixation failure'. There was no difference in reoperation rate or in infection rate. Average displacement of the lateral wall was larger (9mm vs 1,3mm) in the no-cerclage group (p=0,003). The mean duration of surgery in the cerclage group was 28 minutes longer (p=0.003). Cerclage wiring does not lead to higher re-operation, nor higher infection rates. The use of cerclage wire in open reduction is advocated when closed reduction is not satisfactory.


Effect of acute and chronic cholinesterase inhibition with diisopropylfluorophosphate on muscarinic, dopamine, and GABA receptors of the rat striatum.
The effects of acute and chronic administration of diisopropylfluorophosphate (DFP) to rats on acetylcholinesterase (AChE) activity (in striatum, medulla, diencephalon, cortex, and medulla) and muscarinic, dopamine (DA), and gamma-aminobutyric acid (GABA) receptor characteristics (in striatum) were investigated. After a single injection of (acute exposure to) DFP, striatal region was found to have the highest degree of AChE inhibition. After daily DFP injections (chronic treatment), all brain regions had the same degree of AChE inhibition, which remained at a steady level despite the regression of the DFP-induced cholinergic overactivity. Acute administration of DFP increased the number of DA and GABA receptors without affecting the muscarinic receptor characteristics. Whereas chronic administration of DFP for either 4 or 14 days reduced the number of muscarinic sites without affecting their affinity, the DFP treatment caused increase in the number of DA and GABA receptors only after 14 days of treatment; however, the increase was considerably lower than that observed after the acute treatment. The in vitro addition of DFP to striatal membranes did not affect DA, GABA, or muscarinic receptors. The results indicate an involvement of GABAergic and dopaminergic systems in the actions of DFP. It is suggested that the GABAergic and dopaminergic involvement may be a part of a compensatory inhibitory process to counteract the excessive cholinergic activity produced by DFP.


Nicotine effects on human affective functions: a systematic review of the literature on a controversial issue.
The observation that nicotine modulates negative affectivity and has a mood enhancing effect mainly derives from studies conducted in the general population and in clinical samples, mostly in nicotine-deprived subjects. It has been explained by the so called deprivation-reversal hypothesis (i.e., nicotine modulates affect because it alleviates withdrawal symptoms). However, experimental studies suggest that nicotine might modulate different affective functions (e.g., aggressiveness, anxiety) and exert a direct modulating effect on human affectivity. The present paper is a systematic review of the literature aiming at verifying this second hypothesis. A computerized search was carried out (PubMed/Medline 1960-2012). Inclusion criteria were: 1. English language papers published in peer-reviewed journals; 2. experimental/quasi experimental design studies; 3. no deprived adults; 4. inclusion of a control condition; 5. no additional Axis I or II psychiatric disorders. Twenty-one papers met our inclusion criteria. Nicotine was showed to alleviate depression both in smokers and non-smokers, especially if depressed or vulnerable to depression. This effect seemed related to the activation of the dopaminergic brain rewarding system. No clear effect on anxiety was found. Nicotine, thus, seems to exert a direct modulating effect on human mood. Possible limitations of the reviewed studies and future research directions are proposed.


Clinical advances in TNC delivery vectors and their conjugate agents.
Tenascin C (TNC), a glycoprotein that is abundant in the tumor extracellular matrix (ECM), is strongly overexpressed in tumor tissues but virtually undetectable in most normal tissues. Many TNC antibodies, peptides, aptamers, and nanobodies have been investigated as delivery vectors, including 20A1, α-A2, α-A3, α-IIIB, α-D, BC-2, BC-4 BC-8, 81C6, ch81C6, F16, FHK, Ft, Ft-NP, G11, G11-iRGD, GBI-10, 19H12, J1/TN1, J1/TN2, J1/TN3, J1/TN4, J1/TN5, NJT3, NJT4, NJT6, P12, PL1, PL3, R6N, SMART, ST2146, ST2485, TN11, TN12, TNFnA1A2-Fc, TNfnA1D-Fc, TNfnBD-Fc, TNFnCD-Fc, TNfnD6-Fc, TNfn78-Fc, TTA1, TTA1.1, and TTA1.2. In particular, BC-2, BC-4, 81C6, ch81C6, F16, FHK, G11, PL1, PL3, R6N, ST2146, TN11, and TN12 have been tested in human tissues. G11-iRGD and simultaneous multiple aptamers and arginine-glycine-aspartic acid (RGD) targeting (SMART) may be assessed in clinical trials because G11, iRGD and AS1411 (SMART components) are already in clinical trials. Many TNC-conjugate agents, including antibody-drug conjugates (ADCs), antibody fragment-drug conjugates (FDCs), immune-stimulating antibody conjugates (ISACs), and radionuclide-drug conjugates (RDCs), have been investigated in preclinical and clinical trials. RDCs investigated in clinical trials include 111In-DTPA-BC-2, 131I-BC-2, 131I-BC-4, 90Y-BC4, 131I81C6, 131I-ch81C6, 211At-ch81C6, F16124I, 131I-tenatumomab, ST2146biot, FDC 131I-F16S1PF(ab')2, and ISAC F16IL2. ADCs (including FHK-SSL-Nav, FHK-NB-DOX, Ft-NP-PTX, and F16*-MMAE) and ISACs (IL12-R6N and 125I-G11-IL2) may enter clinical trials because they contain components of marketed treatments or agents that were investigated in previous clinical studies. This comprehensive review presents historical perspectives on clinical advances in TNC-conjugate agents to provide timely information to facilitate tumor-targeting drug development using TNC.


Class II histocompatibility antigen expression in human melanocytes transformed by Harvey murine sarcoma virus (Ha-MSV) and Kirsten MSV retroviruses.
Human melanocytes infected with Ki-MSV or Ha-MSV, but not amphotropic MuLV, undergo a series of transformation-related changes that are characteristic of malignant melanoma. These are (a) expression of Ia antigens, in particular DP, DQ, and DR class II histocompatibility gene products, (b) a transformed morphology and ability to grow in soft agar, and (c) a 5-10-fold increase in the cell surface expression of GD3 ganglioside. However, other characteristics of melanoma, such as independence from specific growth factors and loss of adenosine deaminase binding protein were not observed. We conclude that viral ras oncogenes initiate early transformation events in melanocytes, and that Ia antigen expression is a transformation marker in this system.


Non-urgent adult patients in the emergency department: Causes and patient characteristics.
Non-urgent patients are one of the important causes of emergency department (ED) overcrowding. In this study, it is aimed to identify the characteristics of these patients and the reasons why they prefer the ED. This study was conducted during regular office hours. The characteristics of non-urgent patients, their complaints, the frequency of visits to family physicians (FPs), the frequency of using the Central Hospital Appointment System (CHAS) and reasons for preferring the ED were questioned by a questionnaire. This study was conducted on 624 patients. Among them, 326 (52.2%) were male. The mean age was 38.4 years (SD: 14.4). It was identified that 80.3% of the patients had no chronic disease and that 97.4% had health insurance. The most common complaints at presentation were musculoskeletal system pain (25.2%) and upper respiratory tract infections symptoms (19.7%). It was identified that 28.7% of the patients did not prefer to visit their FPs and that 48.6% did not use the CHAS. The reasons of preferring ED were as follows: rapid physical examination (36.4%), not being able to book an earlier appointment at alternative health facilities (30.9%), being close to the facility (12.8%) and being at the hospital for a different reason (12.3%). Among the patients, 20.2% did not express any particular reason. Non-urgent patients who admitted to the ED are mostly middle-aged patients with no chronic disease. They usually visit the ED for preventable reasons. The use of alternative health facilities and CHAS should be encouraged.


The Behavioural Effects of Innovative Litter Developed to Attract Cats.
Urination and/or defecation outside a designated location has been reported as the most common behavioural reason for surrendering a cat and comprises approximately 30% of cat intakes to shelters. The objective of this study was to determine whether cats would increase in-box elimination when provided a plant-based litter product with attractant (ATTRACT) compared to the same plant-based litter product without attractant (PLANT). Sixteen cats were split into two equal cohorts based on availability from the shelter and group-housed in an enriched room with eight identical litter boxes arranged in a circular pattern equidistant from each other. Following a two-week room acclimation and transition period from clay litter to PLANT litter, boxes were designated either PLANT or ATTRACT litter, balancing for cats' prior box location preferences. For 14 days following litter allocation, cat behaviours such as sniffing, digging, covering, urinating, and defecating were video recorded for 12 h daily. The cats urinated more often in the ATTRACT litter, suggesting that they preferred the ATTRACT litter for urination more than the PLANT litter (p < 0.05). The most significant differences observed were between genders, with males spending significantly more time sniffing and performing urination behaviours (p < 0.05). These results suggest that litter with an attractant may be more effective in eliciting usage for urination, as compared to a litter without the additive.


Muscularis mucosae duplication and the musculo-fibrous anomaly in endoscopic mucosal resections for barrett esophagus: implications for staging of adenocarcinoma.
Endoscopic mucosal resection (EMR) is increasingly used for management of Barrett esophagus (BE)-related neoplasia. Duplication of the muscularis mucosae (MM) has been described in BE esophagectomy specimens, where it can pose difficulties with accurate staging of carcinoma. The frequency, morphologic characteristics, and effect of MM duplication in adenocarcinoma staging in EMRs have not yet been evaluated. We studied 122 EMR specimens from 100 patients from 1999 to 2006. The following histologic features were scored: depth of EMR, presence of MM duplication and its extent, prolapse changes (extension of smooth muscle into lamina propria), gland entrapment, and diagnosis (original and study/final). Carcinomas reaching the level of submucosa were classified as invasive adenocarcinoma (INV); those confined to lamina propria or MM were classified as intramucosal adenocarcinoma (IMAC). Of 122 EMRs, 11 (9%) reached mucosa only, 109 (89%) extended to submucosa, and 2 (2%) extended into muscularis propria. MM duplication was present in 67% (75 of 111 specimens that reached at least submucosa). Prolapse changes were noted in 65 (54%) cases and gland entrapment in 67 (56%). Final pathologic diagnoses were 9 (7%) no specialized Barrett mucosa, 4 (3%) BE without dysplasia, 13 (11%) low-grade dysplasia, 51 (42%) high-grade dysplasia, 33 (27%) IMAC, and 12 (10%) INV. EMRs without BE were less likely to show MM duplication (P = 0.01) and there was a trend toward less frequent prolapse change (P = 0.08) and less gland entrapment (P = 0.08) as compared with EMRs with BE. However, there were no significant differences with respect to MM duplication, prolapse change, or gland entrapment between BE with or without dysplasia, IMAC, or INV. Among 33 cases of IMAC, tumor invaded lamina propria in 10 (30%), inner or single MM in 14 (42%), space between duplicated MM in 5 (15%), and outer MM layer in 4(12%). Lymphatic invasion was seen in 2 (10%) cases in which tumor reached the space between MM layers. Overstaging of carcinomas occurred in the original reports in 8 (7%) cases due to misinterpretation of the muscular anatomy, including one case in which the deep MM was interpreted as muscularis propria. These results show that MM duplication is commonly seen in EMR specimens. It is closely associated with the presence of BE but is not affected by neoplastic progression in the Barrett epithelium. Pathologists need to be aware of this distinctive anatomy of BE for accurate staging of adenocarcinomas, particularly to avoid mistaking a thickened outer MM as muscularis propria. Level of IMAC may be a critical feature because of potential access to lymphatic spaces between duplicated MM layers, and we therefore recommend including an explicit statement about the depth of adenocarcinoma invasion rather than using only broad terms such as IMAC or INV in the diagnostic report.


Characterization of two distinct structural classes of selective aldehyde dehydrogenase 1A1 inhibitors.
Aldehyde dehydrogenases (ALDH) catalyze the irreversible oxidation of aldehydes to their corresponding carboxylic acid. Alterations in ALDH1A1 activity are associated with such diverse diseases as cancer, Parkinson's disease, obesity, and cataracts. Inhibitors of ALDH1A1 could aid in illuminating the role of this enzyme in disease processes. However, there are no commercially available selective inhibitors for ALDH1A1. Here we characterize two distinct chemical classes of inhibitors that are selective for human ALDH1A1 compared to eight other ALDH isoenzymes. The prototypical members of each structural class, CM026 and CM037, exhibit submicromolar inhibition constants but have different mechanisms of inhibition. The crystal structures of these compounds bound to ALDH1A1 demonstrate that they bind within the aldehyde binding pocket of ALDH1A1 and exploit the presence of a unique glycine residue to achieve their selectivity. These two novel and selective ALDH1A1 inhibitors may serve as chemical tools to better understand the contributions of ALDH1A1 to normal biology and to disease states.


Expectations, mood, and eating behavior in binge eating disorder. Beware of the bright side.
Sad people may indulge in fattening snacks because they believe that eating will repair their mood. To test whether (1) changes in expectations and mood had an effect on caloric intake and (2) depressive symptoms moderated caloric intake, 73 women with binge eating disorder were randomly assigned to a condition in which expectations about food and emotion were either confirmed or disconfirmed. Subsequently they were shown either an upsetting or an amusing movie clip followed by a taste task. Contrary to our expectations, there were no differences in the four conditions: participants in all four conditions ate comparable amounts of calories. Manipulation of expectations or mood had no effect on caloric intake. However, higher baseline expectations that food is pleasurable and useful as a reward resulted in a higher caloric intake after positive mood induction. Non-depressed individuals ate less after a negative mood induction than did depressed individuals. Interestingly, they also ate less than the group of individuals, depressed and not, whose mood was positively induced. Non-depressed individuals seem to use healthier coping strategies: negative affect signals that the environment poses a problem. Positive affect on the other hand signals that the environment is benign, and thus makes people less vigilant about food intake.


Hand position on steering wheel during driving.
The objective was to study hand position on the steering wheel during driving and differences in hand position within and between the genders. This cross-sectional pilot study was conducted in Ornskoldsvik, Sweden. Photos were taken of drivers on a public road with a speed limit of 70 km/h, and hand position and gender were registered. Hand positions on the steering wheel with one or both hands in a 10 minutes to 2 o'clock position is common, males 55 percent and females 64 percent, during low-risk driving conditions. Symmetric (left-right) hand positions, at 9 and 3, 10 and 2, and finally 11 and 1 o'clock are rare, 6 percent among males and 12 percent among females. The results call for further studies of hand position on the steering wheel during naturalistic driving in traffic areas where rear-end impacts are frequent, particularly because upper hand position might affect spinal posture and thereby increased backset distance between the back of the head and the head restraint (backset), which influences neck injury risk in rear-end impacts.


Restoring tides to reduce methane emissions in impounded wetlands: A new and potent Blue Carbon climate change intervention.
Coastal wetlands are sites of rapid carbon (C) sequestration and contain large soil C stocks. Thus, there is increasing interest in those ecosystems as sites for anthropogenic greenhouse gas emission offset projects (sometimes referred to as "Blue Carbon"), through preservation of existing C stocks or creation of new wetlands to increase future sequestration. Here we show that in the globally-widespread occurrence of diked, impounded, drained and tidally-restricted salt marshes, substantial methane (CH4) and CO2 emission reductions can be achieved through restoration of disconnected saline tidal flows. Modeled climatic forcing indicates that tidal restoration to reduce emissions has a much greater impact per unit area than wetland creation or conservation to enhance sequestration. Given that GHG emissions in tidally-restricted, degraded wetlands are caused by human activity, they are anthropogenic emissions, and reducing them will have an effect on climate that is equivalent to reduced emission of an equal quantity of fossil fuel GHG. Thus, as a landuse-based climate change intervention, reducing CH4 emissions is an entirely distinct concept from biological C sequestration projects to enhance C storage in forest or wetland biomass or soil, and will not suffer from the non-permanence risk that stored C will be returned to the atmosphere.


Engineering and functional characterization of a proton-driven β-lactam antibiotic translocation module for bionanotechnological applications.
Novel approaches in synthetic biology focus on the bottom-up modular assembly of natural, modified natural or artificial components into molecular systems with functionalities not found in nature. A possible application for such techniques is the bioremediation of natural water sources contaminated with small organic molecules (e.g., drugs and pesticides). A simple molecular system to actively accumulate and degrade pollutants could be a bionanoreactor composed of a liposome or polymersome scaffold combined with energizing- (e.g., light-driven proton pump), transporting- (e.g., proton-driven transporter) and degrading modules (e.g., enzyme). This work focuses on the engineering of a transport module specific for β-lactam antibiotics. We previously solved the crystal structure of a bacterial peptide transporter, which allowed us to improve the affinity for certain β-lactam antibiotics using structure-based mutagenesis combined with a bacterial uptake assay. We were able to identify specific mutations, which enhanced the affinity of the transporter for antibiotics containing certain structural features. Screening of potential compounds allowed for the identification of a β-lactam antibiotic ligand with relatively high affinity. Transport of antibiotics was evaluated using a solid-supported membrane electrophysiology assay. In summary, we have engineered a proton-driven β-lactam antibiotic translocation module, contributing to the growing toolset for bionanotechnological applications.


PDGF-stimulated fibroblast proliferation is enhanced synergistically by receptor-recognized alpha 2-macroglobulin.
alpha-Macroglobulins derived from plasma or secreted by macrophages are platelet-derived growth factor (PDGF) binding proteins that compete with cell-surface receptors on fibroblasts for PDGF binding. alpha 2-Macroglobulin (alpha 2M) derived from bovine plasma was tested for its ability to modulate the PDGF-induced proliferation of primary passage rat lung fibroblasts (RLFs) and a human skin fibroblast cell line (CRL 1508). Fibroblasts were grown in 10% fetal bovine serum (FBS) for 24 hr, then washed with serum-free medium before adding serum-free defined medium (SFDM) containing insulin and transferrin. To this medium were added varying concentrations of human plasma-derived AB-PDGF and alpha 2 M, alone or in combination. Receptor-recognized alpha 2M was prepared by treatment with methylamine. Both native alpha 2M and the alpha 2M-methylamine (alpha 2M-MA) were tested for growth promoting activity in the absence or presence of PDGF. After 3 days, a concentration-dependent growth curve of fibroblast proliferation was demonstrated for PDGF alone, with near maximal stimulation reached at 15-20 ng/ml PDGF. alpha 2M and alpha 2M-MA alone had no effect on cell proliferation. However, alpha 2M-MA concentrations above 32 micrograms/ml synergistically enhanced PDGF-stimulated proliferation greater than 100% in the presence of 15 ng/ml PDGF. Native alpha 2M enhanced PDGF-stimulated growth 80-100% above PDGF controls only at low concentrations (32-64 micrograms/ml alpha 2M). High concentrations of native alpha 2M (128-256 micrograms/ml) either had no effect on growth or were inhibitory to PDGF-stimulated growth, depending on the cell type tested. Rat lung fibroblasts were shown to secrete a factor(s) that inhibited the trypsin-binding capacity of native alpha 2M. We further demonstrated that early passage RLFs possess specific cell-surface receptors for [125I]-PDGF and [125I]-alpha 2M-MA, and preincubation of RLFs with alpha 2M-MA increased the specific binding of [125I]-PDGF to the cell surface of these fibroblasts. Considered together, these data support the view that receptor-recognized alpha 2M synergistically enhances the proliferative capacity of PDGF. We postulate that receptor-recognized alpha Ms enhance PDGF-stimulated growth by increasing the local concentration of PDGF at the cell surface, where the PDGF could be released in close proximity to its own receptors.


New models for elevating the practice and status of community-based nursing across the spectrum of cancer care in Central and Eastern Europe.
This supplement comprises an evaluation of Bridging Cancer Care, an initiative of the Bristol-Myers Squibb Foundation first conceived in 2007, addressing disparities in cancer care between Central and Eastern Europe and Western Europe. The strategic focus was refined in 2010 to put particular emphasis on capacity building of nurses in terms of education, training and empowerment. The evaluation was based on review of data and information from the program's monitoring and evaluation framework and from biannual reports submitted by grantees to the Bristol-Myers Squibb Foundation. Eleven of the grantees were selected to develop case studies, which illustrate a) the role of nurses in tobacco cessation, b) expansion of the scope of practice for general practice nurses in health promotion, prevention and early detection of cancer, c) capacity building for nurses in contemporary models of cancer care, care navigation and psychosocial support and d) establishment of nurse training programs in palliative care in Central and Eastern Europe. Between 2010 and 2013, 22 grants were awarded in Russia, Poland, Czech Republic, Hungary and Romania. The evaluation characterized the program's impact in terms of improved health equity, health outcomes, capacity building of nurses and public awareness about cancer. With regard to health equity, all projects targeted disproportionately affected populations (children, poor, rural, ethnic) among whom 35,493 individuals were reached either through cancer screening or community and clinical care. In relation to capacity building, overall 5724 healthcare workers, primarily nurses, received training in various aspects of cancer care, while more than 50,000 patients and more than 470,000 members of the general public were reached through educational initiatives. Most of the programs have been sustained beyond Bristol-Myers Squibb Foundation funding. The positive results were achieved predominantly through greater nurse empowerment, supported by the development of 17 different, customized and nurse-focused curricula. Such training can increase nurses' knowledge and skills as demonstrated by examination testing and evaluation of nurses in the workplace. Several projects also resulted in enhanced nurse leadership attributes and eleven lead to positive changes in models of clinical or community care involving nurses. In eight cases, these changes were subsequently embodied in new health policies.


Zika Virus: Obstetric and Pediatric Anesthesia Considerations.
As of November 2016, the Florida Department of Health (FDH) and the Centers for Disease Control and Prevention have confirmed more than 4000 travel-related Zika virus (ZIKV) infections in the United States with >700 of those in Florida. There have been 139 cases of locally acquired infection, all occurring in Miami, Florida. Within the US territories (eg, Puerto Rico, US Virgin Islands), >30,000 cases of ZIKV infection have been reported. The projected number of individuals at risk for ZIKV infection in the Caribbean and Latin America approximates 5 million. Similar to Dengue and Chikungunya viruses, ZIKV is spread to humans by infected Aedes aegypti mosquitoes, through travel-associated local transmission, via sexual contact, and through blood transfusions. South Florida is an epicenter for ZIKV infection in the United States and the year-round warm climate along with an abundance of mosquito vectors that can harbor the flavivirus raise health care concerns. ZIKV infection is generally mild with clinical manifestations of fever, rash, conjunctivitis, and arthralgia. Of greatest concern, however, is growing evidence for the relationship between ZIKV infection of pregnant women and increased incidence of abnormal pregnancies and congenital abnormalities in the newborn, now medically termed ZIKA Congenital Syndrome. Federal health officials are observing 899 confirmed Zika-positive pregnancies and the FDH is currently monitoring 110 pregnant women with evidence of Zika infection. The University of Miami/Jackson Memorial Hospital is uniquely positioned just north of downtown Miami and within the vicinity of Liberty City, Little Haiti, and Miami Beach, which are currently "hot spots" for Zika virus exposure and transmissions. As the FDH works fervently to prevent a Zika epidemic in the region, health care providers at the University of Miami and Jackson Memorial Hospital prepare for the clinical spectrum of ZIKV effects as well as the safe perioperative care of the parturients and their affected newborns. In an effort to meet anesthetic preparedness for the care of potential Zika-positive patients and perinatal management of babies born with ZIKA Congenital Syndrome, this review highlights the interim guidelines from the Centers for Disease Control and Prevention and also suggest anesthetic implications and recommendations. In addition, this article reviews guidance for the evaluation and anesthetic management of infants with congenital ZIKV infection. To better manage the perioperative care of affected newborns, this article also reviews the comparative anesthetic implications of babies born with related congenital malformations.


Non-invasive investigation of chronic stable angina--a practical overview for medical practitioners.
How does one decide on the best non-invasive test to investigate stable coronary ischaemia? This is a very common question faced by many medical practitioners. Chronic stable angina is a common presentation encountered in general practitice. Upon clinical assessment and risk stratification the patient needs to be investigated further to confirm the diagnosis. The first investigational modality involves a non-invasive test. It is important that practitioners possess a practical knowledge of the array of different tests that are available so that the best suited one for each patient can be chosen. This article aims to compare the efficacy and accuracy and the practical utility of the different non-invasive tests for coronary ischaemia and aid the practitioner in making sound decisions in this regard.


miR-126 Mimic Counteracts the Increased Secretion of VEGF-A Induced by High Glucose in ARPE-19 Cells.
Vascular endothelial growth factor-A (VEGF-A) has a pathologic role in microvascular diabetic complication, such as diabetic retinopathy (DR). miR-126 plays an important role in vascular development and angiogenesis by regulating the expression of VEGF-A. Since levels of miR-126 have been found downregulated in diabetes, this study is aimed at investigating whether hyperglycemia affects expression of miR-126 in a retinal pigment epithelium cell line. ARPE-19 cells were transfected with miR-126 inhibitor or with miR-126 mimic and the respective scramble negative control. After 24 hours, medium was replaced and cells were cultured for 24 hours in normal (CTR) or diabetic condition (HG). Then, we analyzed mRNA levels of miR-126, VEGF-A, PI3KR2, and SPRED1. We also evaluated protein amount of HIF-1α, PI3KR2, and SPRED1 and VEGF-A secretion. The results showed that exposure of ARPE-19 cells to HG significantly decreased miR-126 levels; mRNA levels of VEGF-A and PI3KR2 were inversely correlated with those of miR-126. Overexpression of miR-126 under HG restored HIF-1α expression and VEGF-A secretion to the level of CTR cells. These results indicate that reduced levels of miR-126 may contribute to DR progression by increasing expression of VEGF-A in RPE cells. In addition, we provide evidence that upregulation of miR-126 in RPE cells counteracts the rise of VEGF-A secretion induced by hyperglycemia. In conclusion, our data support a role of miR-126 mimic-approach in counteracting proangiogenic effects of hyperglycemia.


Outcome of patients with localized prostate cancer treated by radiotherapy after confirming the absence of lymph node invasion.
Management of lymph nodes in radiotherapy for prostate cancer is an issue for curative intent. To find the influence of lymph nodes, patients with T1-T3 prostate cancer and surgically confirmed negative nodes were treated with radiotherapy. After lymphadenectomy, 118 patients received photon beam radiotherapy with 66 Gy to the prostate. No adjuvant treatment was performed until biochemical failure. After failure, hormone therapy was administered. Follow-up period was 57 months (mean). Biochemical failure occurred in 47 patients. Few failures were observed in patients with low (24%) and intermediate risks (14%). In contrast, 64% of high-risk patients experienced failure, 97% of whom showed until 36 months. Most patients with failure responded well to hormone therapy. After 15 months (mean), a second biochemical failure occurred in 21% of patients who had the first failure, most of them were high risk. Factors involving failure were high initial and nadir prostate-specific antigen, advanced stage, short prostate-specific antigen-doubling time and duration between radiation and first failure. Failure showed an insufficient reduction in prostate-specific antigen after radiotherapy. Factor for second failure was prostate-specific antigen-doubling time at first failure. Half of high-risk patients experienced biochemical failure, indicating one of the causes involves factors other than lymph nodes. Low-, intermediate- and the other half of high-risk patients did not need to take immediate hormone therapy after radiotherapy. After failure, delayed hormone therapy was effective. Prostate-specific antigen parameters were predictive factors for further outcome.


Modulation of intercellular communication in macrophages: possible interactions between GAP junctions and P2 receptors.
Gap junctions are connexin-formed channels that play an important role in intercellular communication in most cell types. In the immune system, specifically in macrophages, the expression of connexins and the establishment of functional gap junctions are still controversial issues. Macrophages express P2X(7) receptors that, once activated by the binding of extracellular ATP, lead to the opening of transmembrane pores permeable to molecules of up to 900 Da. There is evidence suggesting an interplay between gap junctions and P2 receptors in different cell systems. Thus, we used ATP-sensitive and -insensitive J774.G8 macrophage cell lines to investigate this interplay. To study junctional communication in J774-macrophage-like cells, we assessed cell-to-cell communication by microinjecting Lucifer Yellow. Confluent cultures of ATP-sensitive J774 cells (ATP-s cells) are coupled, whereas ATP-insensitive J774 cells (ATP-i cells), derived by overexposing J774 cells to extracellular ATP until they do not display the phenomenon of ATP-induced permeabilization, are essentially uncoupled. Western-blot and reverse-transcription polymerase chain reaction assays revealed that ATP-s and ATP-i cells express connexin43 (Cx43), whereas only ATP-s cells express the P2X(7) receptor. Accordingly, ATP-i cells did not display any detectable ATP-induced current under whole-cell patch-clamp recordings. Using immunofluorescence microscopy, Cx43 reactivity was found at the cell surface and in regions of cell-cell contact of ATP-s cells, whereas, in ATP-i cells, Cx43 immunoreactivity was only present in cytosolic compartments. Using confocal microscopy, it is shown here that, in ATP-s cells as well as in peritoneal macrophages, Cx43 and P2X(7) receptors are co-localized to the membrane of ATP-s cells and peritoneal macrophages.


Butterfly wing colours: scale beads make white pierid wings brighter.
The wing-scale morphologies of the pierid butterflies Pieris rapae (small white) and Delias nigrina (common jezabel), and the heliconine Heliconius melpomene are compared and related to the wing-reflectance spectra. Light scattering at the wing scales determines the wing reflectance, but when the scales contain an absorbing pigment, reflectance is suppressed in the absorption wavelength range of the pigment. The reflectance of the white wing areas of P. rapae, where the scales are studded with beads, is considerably higher than that of the white wing areas of H. melpomene, which has scales lacking beads. The beads presumably cause the distinct matt-white colour of the wings of pierids and function to increase the reflectance amplitude. This will improve the visual discrimination between conspecific males and females.


[Hazards of development of occupational fluorosis in manufacture of phosphorus-containing mineral products].
Complex studies pertaining to the production of phosphorus-containing mineral products detected no cases of occupational fluorosis among workers. The reasons for fluorosis absence in fluorine-exposed workers were analyzed. The total fluorine load was calculated in workers of the main professions. It was demonstrated that fluorine annual intake of 2-4 g corresponding to the mean-shift concentration of 1-2 mg/m3 (critical levels) required various activities aimed at prevention of occupational fluorosis.


Functional and Physical Interaction between the Arf Activator GBF1 and Hepatitis C Virus NS3 Protein.
GBF1 has emerged as a host factor required for the genome replication of RNA viruses of different families. During the hepatitis C virus (HCV) life cycle, GBF1 performs a critical function at the onset of genome replication but is dispensable when the replication is established. To better understand how GBF1 regulates HCV infection, we have looked for interactions between GBF1 and HCV proteins. NS3 was found to interact with GBF1 in yeast two-hybrid, coimmunoprecipitation, and proximity ligation assays and to interfere with GBF1 function and alter GBF1 intracellular localization in cells expressing NS3. The interaction was mapped to the Sec7 domain of GBF1 and the protease domain of NS3. A reverse yeast two-hybrid screen to identify mutations altering NS3-GBF1 interaction yielded an NS3 mutant (N77D, Con1 strain) that is nonreplicative despite conserved protease activity and does not interact with GBF1. The mutated residue is exposed at the surface of NS3, suggesting it is part of the domain of NS3 that interacts with GBF1. The corresponding mutation in strain JFH-1 (S77D) produces a similar phenotype. Our results provide evidence for an interaction between NS3 and GBF1 and suggest that an alteration of this interaction is detrimental to HCV genome replication.IMPORTANCE Single-stranded, positive-sense RNA viruses rely to a significant extent on host factors to achieve the replication of their genome. GBF1 is such a cellular protein that is required for the replication of several RNA viruses, but its mechanism of action during viral infections is not yet defined. In this study, we investigated potential interactions that GBF1 might engage in with proteins of HCV, a GBF1-dependent virus. We found that GBF1 interacts with NS3, a nonstructural protein involved in HCV genome replication, and our results suggest that this interaction is important for GBF1 function during HCV replication. Interestingly, GBF1 interaction with HCV appears different from its interaction with enteroviruses, another group of GBF1-dependent RNA viruses, in keeping with the fact that HCV and enteroviruses use different functions of GBF1.


Comparative transcriptomics of the model mushroom Coprinopsis cinerea reveals tissue-specific armories and a conserved circuitry for sexual development.
It is well known that mushrooms produce defense proteins and secondary metabolites against predators and competitors; however, less is known about the correlation between the tissue-specific expression and the target organism (antagonist) specificity of these molecules. In addition, conserved transcriptional circuitries involved in developing sexual organs in fungi are not characterized, despite the growing number of gene expression datasets available from reproductive and vegetative tissue. The aims of this study were: first, to evaluate the tissue specificity of defense gene expression in the model mushroom Coprinopsis cinerea and, second, to assess the degree of conservation in transcriptional regulation during sexual development in basidiomycetes. In order to characterize the regulation in the expression of defense loci and the transcriptional circuitries controlling sexual reproduction in basidiomycetes, we sequenced the poly (A)-positive transcriptome of stage 1 primordia and vegetative mycelium of C. cinerea A43mutB43mut. Our data show that many genes encoding predicted and already characterized defense proteins are differentially expressed in these tissues. The predicted specificity of these proteins with regard to target organisms suggests that their expression pattern correlates with the type of antagonists these tissues are confronted with. Accordingly, we show that the stage 1 primordium-specific protein CC1G_11805 is toxic to insects and nematodes. Comparison of our data to analogous data from Laccaria bicolor and Schizophyllum commune revealed that the transcriptional regulation of nearly 70 loci is conserved and probably subjected to stabilizing selection. A Velvet domain-containing protein was found to be up-regulated in all three fungi, providing preliminary evidence of a possible role of the Velvet protein family in sexual development of basidiomycetes. The PBS-soluble proteome of C. cinerea primordia and mycelium was analyzed by shotgun LC-MS. This proteome data confirmed the presence of intracellular defense proteins in primordia. This study shows that the exposure of different tissues in fungi to different types of antagonists shapes the expression pattern of defense loci in a tissue-specific manner. Furthermore, we identify a transcriptional circuitry conserved among basidiomycetes during fruiting body formation that involves, amongst other transcription factors, the up-regulation of a Velvet domain-containing protein.


Cytochrome P-450 CYP2C19 genetic polymorphism and its relation with clopidogrel resistance.
To find out the prevalence of CYP2C19*2 genetic polymorphism in ischaemic heart disease patients, and to determine its relation with clopidogrel resistance in different genotype groups. The cross-sectional study was conducted from August 2015 to December 2019 at the Army Medical College, National University of Medical Sciences, Rawalpindi, Pakistan, and comprised ischaemic heart disease patients of either gender who were on clopidogrel therapy. CYP2C19*2 genotyping of all the patients was carried out through polymerase chain reaction-restriction fragment length polymorphism. Platelet aggregation analysis was done using a light transmission aggregometer. Data was analysed using SPSS 23. Of the 390 patients, 232(59.5%) were males and 158(40.5%) were females. The overall age range was 16-82 years. Clinical indications of clopidogrel were angina 198(50.8%), myocardial infarction 146(37.4%) and acute coronary syndrome 46(11.8%). CYP2C19*2 genotyping showed that 196(50.24%) patients were homozygous wild type carriers (GG or *1/*1), 159(40.8%) were heterozygous carriers (GA or *1/*2), and 35(9%) were homozygous polymorphic allele carriers (AA or *2/*2). Platelet aggregation studies showed that there were 157(80.1%) clopidogrel responders and 39(19.9%) clopidogrel-resistant patients among GG carriers, 118(74.2%) clopidogrel responders and 41(25.8%) clopidogrel-resistant among GA carriers, and 18(51.4%) clopidogrel responders and 17(48.6%) clopidogrel-resistant among AA carriers (p=0.001). Intergroup mean platelet aggregation was significantly different (p=0.025). Allelic frequency of dominant allele *1 and polymorphic variant allele *2 was 0.706(70.6%) and 0.294(29.4), respectively. Homozygous and heterozygous carriers of CYP2C19 allele *2 was found to have higher prevalence of clopidogrel resistance in the studied population.


The MC160 protein of the molluscum contagiosum virus dampens cGAS/STING-induced interferon-β activation.
Molluscum contagiosum virus (MCV) is a poxvirus that causes benign, persistent skin lesions. MCV encodes a variety of immune evasion molecules to dampen host immune responses. Two of these proteins are the MC159 and MC160 proteins. Both MC159 and MC160 contain two tandem death effector domains and share homology to the cellular FLIPs, FADD, and procaspase-8. MC159 and MC160 dampen several innate immune responses such as NF-κB activation and mitochondrial antiviral signaling (MAVS)-mediated induction of type 1 interferon (IFN). The type 1 IFN response is also activated by the cytosolic DNA sensors cyclic GMP-AMP synthase (cGAS) and stimulator of interferon genes (STING). Both cGAS and STING play a vital role in sensing a poxvirus infection. In this study, we demonstrate that there are nuanced differences between both MC160 and MC159 in terms of how the viral proteins modulate the cGAS/STING and MAVS pathways. Specifically, MC160 expression, but not MC159 expression, dampens cGAS/STING-mediated induction of IFN in HEK 293 T cells. Further, MC160 expression prevented the K63-ubiquitination of both STING and TBK1, a kinase downstream of cGAS/STING. Ectopic expression of the MC160 protein, but not the MC159 protein, resulted in a measurable decrease in the TBK1 protein levels as detected via immunoblotting. Finally, using a panel of MC160 truncation mutants, we report that the MC160 protein requires both DEDs to inhibit cGAS/STING-induced activation of IFN-β. Our model indicates MC160 likely alters the TBK1 signaling complex to decrease IFN-β activation at the molecular intersection of the cGAS/STING and MAVS signaling pathways.


Quantitative phase imaging of cells in a flow cytometry arrangement utilizing Michelson interferometer-based off-axis digital holographic microscopy.
We combined Michelson-interferometer-based off-axis digital holographic microscopy (DHM) with a common flow cytometry (FCM) arrangement. Utilizing object recognition procedures and holographic autofocusing during the numerical reconstruction of the acquired off-axis holograms, sharply focused quantitative phase images of suspended cells in flow were retrieved without labeling, from which biophysical cellular features of distinct cells, such as cell radius, refractive index and dry mass, can be subsequently retrieved in an automated manner. The performance of the proposed concept was first characterized by investigations on microspheres that were utilized as test standards. Then, we analyzed two types of pancreatic tumor cells with different morphology to further verify the applicability of the proposed method for quantitative live cell imaging. The retrieved biophysical datasets from cells in flow are found in good agreement with results from comparative investigations with previously developed DHM methods under static conditions, which demonstrates the effectiveness and reliability of our approach. Our results contribute to the establishment of DHM in imaging FCM and prospect to broaden the application spectrum of FCM by providing complementary quantitative imaging as well as additional biophysical cell parameters which are not accessible in current high-throughput FCM measurements.


Kaposi's sarcoma in women with AIDS.
To describe the presentation and incidence of Kaposi's sarcoma (KS) in a cohort of women infected with HIV and to compare their clinical characteristics with men at the same institution. Retrospective chart and database review. Adult clinical AIDS program outpatient clinics at a municipal teaching hospital. One hundred and seven people with KS were found of whom twelve (11.2%) were women. The prevalence of KS in women was 3.6% compared with 9.9% among men (P < 0.001). Women born outside the United States were at increased risk of developing KS (P < 0.05). At initial KS presentation, no difference in HIV stage or CD4 count was found between men and women. Women presented with more advanced KS than men, with increased incidence of non-cutaneous disease (P < 0.001), lymphedema (P < 0.0001), lymph-node disease (P < 0.0001) and visceral disease (P = 0.03). Women had decreased survival after KS diagnosis compared to men, although the difference was not significant (P = 0.41). KS is not a rare diagnosis in HIV-infected women followed at our institution. Although the increased risk of KS in men is most likely to be related to differences in exposure, the sex-related differences in presentation and course may be due in part to delay in diagnosis. KS should be considered in the spectrum of HIV-related complications in women as well as in men.


Willingness to pay: Australian consumers and "on the farm" welfare.
The success of welfare legislation for nonhuman animals rests upon primary producer compliance that, in turn, is affected by public willingness to pay (WTP) for such initiatives. Although the topic of the welfare of animals on farms (and relevant legislation) is becoming increasingly important to the Australian public, there remain relatively few recent assessments of the variables that may affect WTP and, therefore, support initiatives aimed at improving the welfare of animals living on farms. This study surveyed 1,224 community members in Queensland, Australia. The study assessed respondents' self-rated knowledge of, and concern regarding, farm animal welfare. In addition, the survey asked respondents how much more they would be prepared to pay for animal-based products to ensure that they came from a source where the Five Freedoms were met. Although self-rated knowledge and level of concern were found to affect WTP, the study found only concern for farm animal welfare actually predicted consumer behavior. Further analyses showed a potential confound between knowledge levels and locality. This article discusses the implications of this for future initiatives to increase WTP.


[Standards and recommendations for hospital environmental hygiene].
The hospital laboratory has important responsibilities in the survey, control and prevention of nosocomial infections. Contamination of environment (surfaces, air, liquids) has been implicated in nosocomial infections. It is essential to develop a monitoring system for biocontamination control in the controlled environment areas. Classification of zones at risk (low, medium, high and very high risk) should be performed according to relevant guidelines or regulations where these exist. According to the classification of the zone at risk appropriate levels of biocontamination will be assigned. Standards for acceptable levels of microbiologic contamination will be suggested because no uniform agreement have been achieved because of the lack of correlation between these levels and occurrence of clinical infection.


Electron probe X-ray microanalysis studies on the distribution change of intra- and extracellular calcium in the elongation zone of horizontally reoriented soybean roots.
To clarify the contribution of Ca to the gravitropic response, quantitative X-ray microanalyses were performed on cryosections of roots of soybean seedlings reoriented horizontally from their original vertical orientation. After reorientation, the roots bent gradually toward the ground at the elongation zone. The concentrations of Ca in the cell walls, cytoplasmic matrices and central vacuoles of cortical cells were measured in the upper and lower halves of the elongation zone at 0, 30, 60 and 120 min after reorientation. The Ca concentration did not significantly change in the cytoplasmic matrices or vacuoles. Additionally, the Ca concentration did not change significantly in cell walls at 30 min after reorientation; however, beyond 30 min, this concentration significantly increased gradually in the lower half of the elongation zone and decreased in the upper half of the elongation zone, indicating a typical asymmetrical distribution of Ca. These results suggest that Ca moves apoplastically in soybean roots to produce an asymmetrical Ca distribution in the elongation zone, which contributes to root curvature. The possible role of Ca in accelerating or repressing the effect of auxin is also discussed in this study.


Hypertension, the renin-angiotensin system, and the risk of lower respiratory tract infections and lung injury: implications for COVID-19.
Systemic arterial hypertension (referred to as hypertension herein) is a major risk factor of mortality worldwide, and its importance is further emphasized in the context of the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection referred to as COVID-19. Patients with severe COVID-19 infections commonly are older and have a history of hypertension. Almost 75% of patients who have died in the pandemic in Italy had hypertension. This raised multiple questions regarding a more severe course of COVID-19 in relation to hypertension itself as well as its treatment with renin-angiotensin system (RAS) blockers, e.g. angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs). We provide a critical review on the relationship of hypertension, RAS, and risk of lung injury. We demonstrate lack of sound evidence that hypertension per se is an independent risk factor for COVID-19. Interestingly, ACEIs and ARBs may be associated with lower incidence and/or improved outcome in patients with lower respiratory tract infections. We also review in detail the molecular mechanisms linking the RAS to lung damage and the potential clinical impact of treatment with RAS blockers in patients with COVID-19 and a high cardiovascular and renal risk. This is related to the role of angiotensin-converting enzyme 2 (ACE2) for SARS-CoV-2 entry into cells, and expression of ACE2 in the lung, cardiovascular system, kidney, and other tissues. In summary, a critical review of available evidence does not support a deleterious effect of RAS blockers in COVID-19 infections. Therefore, there is currently no reason to discontinue RAS blockers in stable patients facing the COVID-19 pandemic.


Occupational health for hospital workers.
Hospitals present a variety of infectious, chemical and physical hazards to their workers. Important pathogens include AIDS, hepatitis B and rubella viruses and Mycobacterium tuberculosis. Ethylene oxide is probably the greatest chemical hazard, but anesthetic gases, antineoplastic drugs and skin irritants or sensitizers are significant hazards as well. Hospitals also have poor safety records. A well-organized occupational health service that includes a physician, or a nurse with medical backup, and good records saves more than it costs.


Antigenicity and immunogenicity of a trimeric envelope protein from an Indian clade C HIV-1 isolate.
Human immunodeficiency virus type 1 (HIV-1) isolates from India mainly belong to clade C and are quite distinct from clade C isolates from Africa in terms of their phylogenetic makeup, serotype, and sensitivity to known human broadly neutralizing monoclonal antibodies. Because many of these properties are associated with the envelope proteins of HIV-1, it is of interest to study the envelope proteins of Indian clade C isolates as part of the ongoing efforts to develop a vaccine against HIV-1. To this end, we purified trimeric uncleaved gp145 of a CCR5 tropic Indian clade C HIV-1 (93IN101) from the conditioned medium of 293 cells. The purified protein was shown to be properly folded with stable structure by circular dichroism. Conformational integrity was further demonstrated by its high affinity binding to soluble CD4, CD4 binding site antibodies such as b12 and VRC01, quaternary epitope-specific antibody PG9, and CD4-induced epitope-specific antibody 17b. Sera from rabbits immunized with gp145 elicited high titer antibodies to various domains of gp120 and neutralized a broad spectrum of clade B and clade C HIV-1 isolates. Similar to other clade B and clade C envelope immunogens, most of the Tier 1 neutralizing activity could be absorbed with the V3-specific peptide. Subsequent boosting of these rabbits with a clade B HIV-1 Bal gp145 resulted in an expanded breadth of neutralization of HIV-1 isolates. The present study strongly supports the inclusion of envelopes from Indian isolates in a future mixture of HIV-1 vaccines.


Toxoplasma gondii infection in cats: ABCD guidelines on prevention and management.
Toxoplasma gondii infection is common in cats, but the clinical disease is rare. Up to 50% of cats, especially free-roaming ones, have antibodies indicating infection and the presence of cystic stages. Clinical signs only appear in few cats when they become immunosuppressed - in these situations cystic stages can be reactivated. Commonly affected are the central nervous system (CNS), muscles, lungs and eyes. HUMAN INFECTION: Cats can pose a risk for humans when they shed oocysts. However, this happens only once in their lifetime, usually only for 3-10 days after ingestion of tissue cysts. Thus, cats that have antibodies to T gondii no longer shed oocysts, and do not pose a risk to humans.


Hepatitis C for addiction professionals.
A disease whose reputation is often worse than its reality, hepatitis C is usually benign. Most infected individuals do not experience symptoms requiring treatment, and roughly half of those treated will become free of detectable virus for an extended, perhaps permanent, period. Moreover, a growing body of data suggests that drug users can attain successful treatment outcomes, even when not completely abstinent. Addiction professionals belong in the forefront of prevention and management of this disease. We can assist our patients by helping them stabilize their lifestyles, correcting misperceptions about the disease, teaching prevention and health maintenance, promoting access to diagnosis and treatment, monitoring for treatment side effects, and providing encouragement to remain in treatment.


Academic progression models in nursing: design decisions faced by administrators in four case studies.
Although nursing education pathways have expanded access to the profession, fragmentation accompanying these entry points has created uncertainty among students about the desired end point, questionable efficiency and effectiveness of reaching career goals, and unclear merging mechanisms to enable seamless, linear progression. In response to these challenges and in anticipation of greater demands on nurses due to health reform, the Institute of Medicine (IOM) examined the capacity of the nursing workforce and proposed a transformative blueprint for change that relies on an education system to promote seamless academic progression. Despite support for this recommendation, little research exists regarding the best way to achieve the IOM's vision. This study examined the most promising practices in design and implementation of alternative pathways for academic progression in nursing. Four case studies are presented that explore the challenges of designing alternative pathways and identify performance measures to assist with developing such programs.


Meta-fibrosis links positive energy balance and mitochondrial metabolism to insulin resistance.
Obesity and insulin resistance often emerge from positive energy balance and generally are linked to low-grade inflammation. This low-grade inflammation has been called "meta-inflammation" because it is a consequence of the metabolic dysregulation that can accompany overnutrition. One means by which meta-inflammation is linked to insulin resistance is extracellular matrix expansion secondary to meta-inflammation, which we define here as "meta-fibrosis". The significance of meta-fibrosis is that it reflects a situation in which the extracellular matrix functions as a multi-level integrator of local (for example, mitochondrial reactive oxygen species production) and systemic (for example, inflammation) inputs that couple to cellular processes creating insulin resistance. While adipose tissue extracellular matrix remodeling has received considerable attention, it is becoming increasingly apparent that liver and skeletal muscle extracellular matrix remodeling also contributes to insulin resistance. In this review, we address recent advances in our understanding of energy balance, mitochondrial energetics, meta-inflammation, and meta-fibrosis in the development of insulin resistance.


Improvements in factor VIII inhibitor detection: From Bethesda to Nijmegen.
All methods for the detection of factor VIII (FVIII) inhibitors are based on the measurement of inactivation of FVIII in a mixture of the test plasma containing the putative inhibitor and an exogenous source of FVIII. Various types of assays have been developed since the first inhibitor was described in 1941. Nowadays, two methods are preferably used, the Bethesda assay and the Nijmegen assay. Although the Nijmegen assay shows a better specificity and intra- and interlaboratory variation, it is still hampered by several limitations related to assay characteristics (pH, temperature, and time of incubation), type of control sample, and the von Willebrand factor content of the assay mixture. Epitope specificity plays an important role in the reliability of functional assays because inhibitors against the C2 domain are more difficult to quantify compared with inhibitors against the A2 domain. Finally, lupus anticoagulants can interfere with inhibitor assays, resulting in aberrant results. This report describes in detail the various problems encountered with the assays used in the quantification of functional FVIII inhibitors.


[DSA for the imaging of tumor-caused vascular changes and complications during local chemotherapy of the liver via the portal system].
In 18 patients with primary or secondary liver tumours, 38 digital subtraction angiographies (DSA) of totally implanted catheter systems for liver perfusion were performed during a period of 8 months. The systems had been used for an average of 6.9 months. In 22 out of 38 examinations secondary reactions of liver arteries were observed, in 7 the therapeutic regimen was changed after DSA. Patients with an extensive tumour involvement of the liver showed mural thromboses or obstructions of liver arteries relatively more often (4 of 7) than patients with smaller size tumours (2 of 11). In 7 cases the therapeutic regimen was changed after DSA. DSA of implanted liver catheters is a valuable, well tolerated, easily and rapidly performed method.


It's About Time: Rapid Implementation of a Hub-and-Spoke Care Delivery Model for Tertiary-Integrated Complex Care Services in a Northern Ontario Community.
Children with medical complexity (CMC) in rural and northern communities have more difficulty accessing subspecialty health providers than those in urban centres. This article describes an alignment cascade in which leaders engaged peers and staff to rapidly roll out the implementation of a sustainably designed complex care model, integrated in the Champlain Complex Care Program and delivered in Timmins, Ontario. The Provincial Council for Maternal and Child Health's Complex Care for Kids Ontario (CCKO) strategy supports the implementation and expansion of a hub-and-spoke model of interprofessional complex care for CMC and their families. A nurse practitioner is the primary point of contact for the family and oversees coordination and integration of care; regional CCKO programs are committed to building capacity to provide safe, high-quality care for CMC in communities closer to their homes.


Anisotropic modulation of magnetic properties and the memory effect in a wide-band (011)-Pr0.7Sr0.3MnO3/PMN-PT heterostructure.
Memory effect of electric-field control on magnetic behavior in magnetoelectric composite heterostructures has been a topic of interest for a long time. Although the piezostrain and its transfer across the interface of ferroelectric/ferromagnetic films are known to be important in realizing magnetoelectric coupling, the underlying mechanism for nonvolatile modulation of magnetic behaviors remains a challenge. Here, we report on the electric-field control of magnetic properties in wide-band (011)-Pr0.7Sr0.3MnO3/0.7Pb(Mg1/3Nb2/3)O3-0.3PbTiO3 heterostructures. By introducing an electric-field-induced in-plane anisotropic strain field during the cooling process from room temperature, we observe an in-plane anisotropic, nonvolatile modulation of magnetic properties in a wide-band Pr0.7Sr0.3MnO3 film at low temperatures. We attribute this anisotropic memory effect to the preferential seeding and growth of ferromagnetic (FM) domains under the anisotropic strain field. In addition, we find that the anisotropic, nonvolatile modulation of magnetic properties gradually diminishes as the temperature approaches FM transition, indicating that the nonvolatile memory effect is temperature dependent. By taking into account the competition between thermal energy and the potential barrier of the metastable magnetic state induced by the anisotropic strain field, this distinct memory effect is well explained, which provides a promising approach for designing novel electric-writing magnetic memories.


Bioactive extracellular matrix fragments in lung health and disease.
The extracellular matrix (ECM) is the noncellular component critical in the maintenance of organ structure and the regulation of tissue development, organ structure, and cellular signaling. The ECM is a dynamic entity that undergoes continuous degradation and resynthesis. In addition to compromising structure, degradation of the ECM can liberate bioactive fragments that cause cellular activation and chemotaxis of a variety of cells. These fragments are termed matrikines, and their cellular activities are sentinel in the development and progression of tissue injury seen in chronic lung disease. Here, we discuss the matrikines that are known to be active in lung biology and their roles in lung disease. We also consider the use of matrikines as disease markers and potential therapeutic targets in lung disease.


Dopamine-glutamate interactions in the basal ganglia.
In an attempt to formulate a working hypothesis of basal-ganglia functions, arguments are considered suggesting that the basal ganglia are involved in a process of response selection i.e. in the facilitation of "wanted" and in the suppression of "unwanted" behaviour. The meso-accumbal dopamine-system is considered to mediate natural and drug-induced reward and sensitization. The meso-striatal dopamine-system seems to fulfill similar functions: It may mediate reinforcement which strengthens a given behaviour when elicited subsequently, but which is not experienced as reward or hedonia. Glutamate as the transmitter of the corticofugal projections to the basal ganglia nuclei and of the subthalamic neurons is critically involved in basal ganglia functions and dysfunctions; for example Parkinson's disease can be considered to be a secondary hyperglutamatergic disease. Additionally, glutamate is an essential factor in the plasticity response of the basal-ganglia. However, opposite to previous suggestions, the NMDA-receptor blocker MK-801 does not prevent psychostimulant- nor morphine-induced day to day increase (sensitization) of locomotion. Also the day to day increase of haloperidol-induced catalepsy was not prevented by MK-801.


Study of an anti-arrhythmic agent, disopyramide, in delayed action form ('Ritmoforine' Retard).
A study was carried out in 10 patients with ventricular dysrhythmias to determine serum levels and effectiveness of treatment with a new delayed-action formulation of disopyramide. Patients received 1 tablet (322.5 mg disopyramide phosphate) twice daily and were monitored constantly. A therapeutically effective level of 3 mg/l was achieved in most cases after 24 hours and in 8 out of the 10 patients the levels remained reasonably stable during the 4 days of observation. It is suggested that adjustment of dosage is advisable in patients with renal dysfunction or left heart failure. Although the new formulation provided a good alternative to the standard preparation of disopyramide, which is usually given on a 4-times daily regimen, it is recommended that the standard capsules should be used during the first 24 hours of treatment to ensure that effective blood levels are achieved rapidly.


Disease-specific gender differences among total knee arthroplasty candidates.
Women with knee osteoarthritis are less likely to undergo joint replacement despite greater self-reported disability. The primary aim of the present study was to assess gender differences in the type and magnitude of osteoarthritis-related impairment prior to knee arthroplasty. Two hundred and twenty-one knee arthroplasty candidates (ninety-five men and 126 women) and forty-four healthy gender, age, and body mass index-matched individuals were tested. Individuals with contralateral limb injury or abnormality, cardiovascular disease, neurological impairment, and medical conditions limiting activity were excluded. Collected data included Medical Outcomes Study Short Form-36 mental and physical component scores, the Knee Outcome Survey Activities of Daily Living Scale score, knee range of motion, timed up-and-go test time, stair-climb test time, six-minute walk distance, normalized quadriceps strength, and volitional muscle activation. Women in the arthroplasty group had lower Short Form-36 and Knee Outcome Survey scores, longer timed up-and-go test and stair-climb test times, shorter six-minute walk distances, and lower normalized quadriceps strength compared with men. Healthy women had longer stair-climb test times and shorter six-minute walk distances in comparison with healthy men. Between-group comparisons revealed that women in both the control group and the arthroplasty group had reduced normalized quadriceps strength in comparison with men, that healthy women had higher voluntary muscle activation in comparison with healthy men, and that female arthroplasty candidates had lower activation levels in comparison with male candidates. Observed gender differences in strength and function appear to be inherent but are magnified in arthroplasty candidates. Strength and functional decline should be closely monitored in women with knee osteoarthritis to serve as an indicator of worsening condition, and preoperative interventions should reflect these gender-specific impairments.


Pulmonary dysfunction in systemic lupus erythematosus without pulmonary symptoms.
Pulmonary function was measured in a group of 28 patients with systemic lupus erythematosus (SLE) who were free of pulmonary involvement at the time of the study. When compared with age and sex matched controls, the SLE patients had a pattern of restriction with reduced lung volumes and vital capacity. Diffusing capacity was reduced in proportion to the reduction in lung volume. This is felt to be most compatible with inapparent pleural thickening resulting in impaired lung expansion. There was no evidence of airway obstruction on maximal expiratory flow-volume curves. The effect of cigarette smoking in the SLE patients was a reduction in flows at low lung volumes, which was indistinguishable from the effects in the control smokers. Both SLE and control smokers had a significant reduction in DL/VA when compared with control nonsmokers. Pulmonary function was not influenced by the presence of renal disease.


Identification of a testicular odorant receptor mediating human sperm chemotaxis.
Although it has been known for some time that olfactory receptors (ORs) reside in spermatozoa, the function of these ORs is unknown. Here, we identified, cloned, and functionally expressed a previously undescribed human testicular OR, hOR17-4. With the use of ratiofluorometric imaging, Ca2+ signals were induced by a small subset of applied chemical stimuli, establishing the molecular receptive fields for the recombinantly expressed receptor in human embryonic kidney (HEK) 293 cells and the native receptor in human spermatozoa. Bourgeonal was a powerful agonist for both recombinant and native receptor types, as well as a strong chemoattractant in subsequent behavioral bioassays. In contrast, undecanal was a potent OR antagonist to bourgeonal and related compounds. Taken together, these results indicate that hOR17-4 functions in human sperm chemotaxis and may be a critical component of the fertilization process.


Tolerability and safety of alosetron during long-term administration in female and male irritable bowel syndrome patients.
Alosetron (Lotronex) is a new therapeutic agent for irritable bowel syndrome (IBS) in women with diarrhea-predominant IBS. This multicenter randomized, double-blind, placebo-controlled study assessed the safety and tolerability of alosetron during long-term (< or = 12 months) treatment. A total of 859 subjects (637 female and 222 male) with IBS were enrolled from 130 sites in the United States and were randomized 3:1 to receive 1 mg alosetron or placebo b.i.d. for 48 wk; of the subjects, 649 (76%) were randomized to the alosetron group and 212 (24%) to the placebo group. Of the original group, 850 subjects received at least one dose of alosetron (n = 640) or placebo (n = 210). In all, 59% of the subjects completed the study. Safety data were similar in treatment groups and within age, sex, racial origin, and hormone use. Adverse events were reported by 83% (530/640) and 76% (159/210) of subjects in the alosetron and placebo groups, respectively, (p < 0.05) and were similar with the exception of constipation; 32% of subjects receiving alosetron reported constipation, compared to 5% in the placebo group (p < 0.001). Most reports (72%) of constipation were of mild or moderate severity, and 66% of subjects with constipation had single episode of 8 days median duration. Constipation occurred a median of 13 days after initiating treatment and resolved spontaneously, with laxative, or after a brief interruption of therapy. Of the subjects, 4% (11/210) in the alosetron and 5% (28/ 640) in the placebo group experienced serious adverse events. Two deaths occurred in subjects with pre-existing cardiovascular risk factors; neither death was attributed to the study drug. Alosetron 1 mg b.i.d. for 12 months was well tolerated. Constipation is the most frequent adverse event, with a higher incidence of transient constipation in alosetron-treated patients, typically occurring in the first month of treatment.


Protection against Salmonella typhi infection in mice after immunization with outer membrane proteins isolated from Salmonella typhi 9,12,d, Vi.
The current studies were undertaken to assess the ability of the outer membrane proteins (OMPs) of Salmonella typhi to induce protection against challenge with the bacteria in mucin. OMPs were isolated as described by Schnaitman (J. Bacteriol. 108:553-556, 1971) and were found to be contaminated with approximately 4% lipopolysaccharide (LPS). Immunization with as little as 30 micrograms of OMPs conferred 100% protection to mice challenged with up to 1,000 50% lethal doses (LD50) of two strains of S. typhi (9,12,d, Vi and Ty2). In addition, 30% protection against challenge with up to 500 LD50 of Salmonella typhimurium was achieved. Immunization with LPS at doses equivalent to those found in the OMPs was considerably inferior to the OMPs in the induction of an immune status. Moreover, LPS was effective only when the challenge was performed with S. typhi 9,12,d, Vi (40% protection to 100 LD50). An antiserum raised in rabbits reacted mainly against the bands of the molecular weights corresponding to the so-called porins contained in the OMP preparation as shown by Western blotting (immunoblotting). This rabbit antiserum protected 100% of mice against challenge with 100 LD50 of either strain of S. typhi and 80% of mice against challenge with the same LD50 of S. typhimurium. These results indicate the usefulness of OMPs in the induction of active immunity against S. typhi in mice.


Apomorphine-induced emesis in dogs: differential sensitivity to established and novel dopamine D2/5-HT(1A) antipsychotic compounds.
Small rodents (mice, rats) are the species of choice for evaluating the pharmacology of centrally acting compounds, such as antipsychotics, whereas toxicology data are routinely obtained from other species (rabbits, dogs, monkeys). Whilst there is a substantial number of "therapeutically relevant" pharmacological models for "antipsychotic-like" activity in small rodents, based on hyperdopaminergic or hypoglutamatergic/NMDA approaches, there is a remarkable paucity of such models in other species. Here, we compared the efficacy and potency of reference and new generation dopamine D2/5-HT(1A) putative antipsychotics, administered orally, against apomorphine-induced emesis in dogs, a model of central D2 receptor activation that can be implemented with relative ease. Risperidone potently and fully (10 microg/kg) prevented emesis/retching induced by 0.1 mg/kg s.c. apomorphine. SLV313 and F15063 (D2 receptor antagonists/5-HT(1A) receptor agonists) also abolished emesis/retching, albeit less potently than risperidone (minimal effective dose, MEDs: 10 and 40 microg/kg, respectively). The D2 receptor partial agonists/5-HT(1A) receptor agonists aripiprazole and bifeprunox, (up to 80 microg/kg) only partially attenuated emesis, as did the peripheral D2 receptor antagonist domperidone. Under the present experimental conditions, haloperidol was only efficacious at the highest dose tested (320 microg/kg). To summarize, dogs are very sensitive to the dopaminergic blocking effects of antipsychotics in this model of D2 receptor activation. This model can thus be advantageously used to investigate the pharmacological activity of novel D2 receptor antagonists/partial agonists in dogs.


Promoting professionalism via a video-based educational workshop for academic hospitalists and housestaff.
Unprofessional behavior can compromise care and detract from the hospital learning environment. Discrepancy between professional behaviors formally taught and what is witnessed has become increasingly evident. With funding from the American Board of Internal Medicine Foundation, a workshop was developed to address unprofessional behaviors related to inpatient care previously identified in a multi-institution survey. The aims were to utilize video-based education to illustrate unprofessional behaviors, how faculty play a role in promoting such behaviors, and facilitate reflection regarding motivation for and prevention of these behaviors. Hospitalists and housestaff at 3 Chicago-area academic hospitals and 1 community teaching affiliate participated. Videos were debriefed, identifying barriers to professional behavior and improvement strategies. A postworkshop survey assessed beliefs on behaviors and intent to change practice. Forty-four (53%) faculty and 244 (68%) residents (postgraduate year 1 and greater) participated. The workshop was well received, with 89% reporting it "useful and effective." Two-thirds expressed intent to change behavior. Most (86%) believed videos were realistic and effective. Those who perceived videos as "very realistic" were more likely to report intent to change behavior (93% vs 53%, P = 0.01). Video-based education is a feasible way to promote reflection and address unprofessional behaviors among providers and may positively impact the learning environment.


Vacuolar degradation of rat liver CYP2B1 in Saccharomyces cerevisiae: further validation of the yeast model and structural implications for the degradation of mammalian endoplasmic reticulum P450 proteins.
Mammalian hepatic cytochromes P450 (P450s) are endoplasmic reticulum (ER)-anchored hemoproteins with highly variable half-lives. CYP3A4, the dominant human liver drug-metabolizing enzyme, and its rat liver orthologs undergo ubiquitin (Ub)-dependent 26S proteasomal degradation after suicide inactivation or after heterologous expression in Saccharomyces cerevisiae. In contrast, rat liver CYP2C11 is degraded by the vacuolar "lysosomal" pathway when similarly expressed in yeast. The structural determinants that commit P450s to proteasomal or lysosomal degradation are unknown. To further validate S. cerevisiae as a model for exploring mammalian P450 turnover, the degradation of phenobarbital-inducible liver CYP2B1, an enzyme reportedly degraded via the rat hepatic autophagic-lysosomal pathway, was examined in a yeast strain (pep4delta) deficient in vacuolar degradation and its isogenic wild-type control (PEP4). Although CYP2B1 was equivalently expressed in both strains during early logarithmic growth, its degradation was retarded in pep4delta strain, remaining at a level 5-fold higher than that in PEP4 yeast when monitored at the stationary phase. No comparable CYP2B1 stabilization was detected in yeast genetically deficient in the ER Ub-conjugating enzyme Ubc6p or Ubc7p or defective in 19S proteasomal subunit Hrd2p. Thus, as in the rat liver, CYP2B1 is a target of vacuolar/lysosomal rather than proteasomal degradation in yeast, thereby further validating this model for mammalian P450 turnover. It is intriguing that a chimeric protein, CYP2B1-3A4CT, with the CYP3A4 C-terminal heptapeptide grafted onto the CYP2B1 C terminus, was proteasomally degraded after similar expression. Such diversion of CYP2B1 from its predominantly vacuolar degradation suggests that the CYP3A4 heptapeptide could either actively signal its proteasomal degradation or block its vacuolar proteolysis.


Comparison of identifications of human and animal source gram-negative bacteria by API 20E and crystal E/NF systems.
This study compared the abilities of API 20E and BBL Crystal E/NF identification systems to correctly identify human and animal source gram-negative bacilli of known identifications, as provided by the American Type Culture Collection, Rockville, Md., and the Research Diagnostic and Investigative Laboratory, Columbia, Mo. Also addressed in the comparison are the cost, the relative ease of performing and interpreting the tests, and the potential problems surrounding each system. The two systems were comparable in terms of their respective costs and abilities to identify the bacteria tested. The cost per test was calculated as $4.69 for API 20E and $4.62 for Crystal E/NF. Of the animal source bacteria tested, Crystal E/NF identified 68% to the correct genus and species and 90% to the correct genus or group. The remaining 10% of the animal source bacteria were unidentified by Crystal. Human source bacteria tested by BBL Crystal E/NF gave very similar results: 47% correctly identified to genus and species, 90% correctly identified to genus or group, 7% unidentified, and 3% incorrectly identified. API 20E results were as follows for animal source bacteria: 53% correctly identified to genus and species, 76% correctly identified to genus or group, and 24% unidentified; the results for human source bacteria were as follows: 40% correctly identified to genus and species, 83% correctly identified to genus or group, and 17% unidentified. API 20E has a slightly more labor-intensive protocol for setting up the test than BBL Crystal E/NF but produced fewer questionable results.


Outcome analysis for stage IE and IIE thyroid lymphoma.
Previous reports have revealed modest results in the management of thyroid lymphoma with radiotherapy alone. This retrospective report evaluates the outcome of patients treated for thyroid lymphoma with radiotherapy alone and with combined modality therapy (chemotherapy and radiotherapy) at a single institution. Twenty-seven patients with stages IE and IIE non-Hodgkin's lymphoma of the thyroid gland were treated between 1960 and 1998 at Barnes-Jewish Hospital, of which 14 patients were stage IE and 13 patients were stage IIE. The median age at diagnosis was 67 years, and there were 21 females and 6 males evaluated. The median follow-up time was 38 months (range: 3-279 months). All patients had histologically proven non-Hodgkin's lymphoma, of which 22 patients (81%) were intermediate grade. Treatment consisted of radiotherapy alone in 19 patients and a combined modality therapy in 8 patients. The median radiation dose to the thyroid bed was 44 Gy, and most patients received a doxorubicin-containing regimen administered prior to radiotherapy. Patient, tumor, and treatment-related characteristics were evaluated using Cox regression analysis. Local-regional tumor control, disease-free survival (DFS), and overall survival (OS) were calculated using the Kaplan-Meier method. Four patients had local relapse in this series, with a crude local tumor control rate of 85%. No factor was determined to be significant for local tumor control. The actuarial 5-year DFS and OS for the entire cohort were 57%, and 56%, respectively. In terms of DFS, both age and stage were statistically significant. The 5-year actuarial DFS for patients less than age 65 years was 83% versus 37% for those more than this age (p = 0.024). Furthermore, the 5-year actuarial DFS for patients with stage I and II disease was 69% and 45%, respectively (p = 0.022). In multivariate analysis, age continued to be significant for DFS (p = 0.049). Overall survival analysis revealed age, local tumor control, and stage to be significant in univariate analysis. Multivariate analysis was further carried out using Cox proportional hazard model, and it revealed age (p = 0.006) and local tumor control (p = 0.007) to be significant. Primary thyroid gland lymphomas have a favorable outcome with appropriate therapy, but prognosis depends on both clinical stage and age at presentation. Because of the risk of both local-regional and distant failure, combined modality approaches that use chemotherapy with radiotherapy are warranted for intermediate- and high grade thyroid lymphoma.


Assessing bimodality to detect the presence of a dual cognitive process.
Researchers have long sought to distinguish between single-process and dual-process cognitive phenomena, using responses such as reaction times and, more recently, hand movements. Analysis of a response distribution's modality has been crucial in detecting the presence of dual processes, because they tend to introduce bimodal features. Rarely, however, have bimodality measures been systematically evaluated. We carried out tests of readily available bimodality measures that any researcher may easily employ: the bimodality coefficient (BC), Hartigan's dip statistic (HDS), and the difference in Akaike's information criterion between one-component and two-component distribution models (AIC(diff)). We simulated distributions containing two response populations and examined the influences of (1) the distances between populations, (2) proportions of responses, (3) the amount of positive skew present, and (4) sample size. Distance always had a stronger effect than did proportion, and the effects of proportion greatly differed across the measures. Skew biased the measures by increasing bimodality detection, in some cases leading to anomalous interactive effects. BC and HDS were generally convergent, but a number of important discrepancies were found. AIC(diff) was extremely sensitive to bimodality and identified nearly all distributions as bimodal. However, all measures served to detect the presence of bimodality in comparison to unimodal simulations. We provide a validation with experimental data, discuss methodological and theoretical implications, and make recommendations regarding the choice of analysis.


Prevention of limb function deterioration in patients with cerebral infarction by clinical nursing pathway management.
To analyze the application effect of clinical nursing pathway in patients with cerebral infarction (CI) and its influence on the deterioration of limb function, so as to find effective prevention methods. A total of 80 patients with CI admitted to our hospital from November 2020 to May 2022 were included in the study. The subjects were divided into two groups based on different nursing interventions, with one group receiving clinical nursing pathway intervention, referred to as the nursing group (n = 40), and the other group receiving standard nursing care, referred to as the routine group (n = 40). The limb function, neurological function, mobility and quality of life before and after intervention were analyzed, and the incidence of safety endpoints after 3 months of follow-up was observed.The results showed that before the intervention, there were no significant differences in each function and index of the study subjects (P > 0.05). After the intervention, the limb function, neurological function, mobility and quality of life of the two groups were higher than those before the intervention, and the degree of improvement was higher in the nursing group (P < 0.05). At the same time, the adverse events in the nursing group were significantly less than those in the conventional group (P < 0.05).It is suggested that clinical nursing management pathway can significantly reduce the deterioration of limb function of patients with CI, improve their mobility and quality of life, which is worthy of clinical promotion.


Urolithiasis is associated with low serum testosterone levels in men.
To evaluate the relationship among urolithiasis, metabolic syndrome (MetS) and serum testosterone (T) level in men. 513 men older than 18 years were enrolled in this study: 313 of the subjects had a history of stones (group 1) and 200 had no history of stones (controls, group 2). Early morning T levels were recorded and anthropometric measurements were investigated to evaluate MetS. Analyses were completed using chi-square tests. Serum T level was lower in stone forming patients than control subjects and 161 (%51.4) men in group 1 and 92 (%46) men in group 2 were diagnosed with metabolic syndrome. T level was found lower limit (< 285 ng/dl) in the MetS and urolithiasis group (p 0.002, OR 2.71). We found low testosterone levels in the patients with stone disease and prevalence of the MetS in men with urolithiasis was higher than in men without stone disease. Our findings show that levels of testosterone had no effect on stone formation, but the factors that cause stone formation can have an effect on the level of testosterone.


Characterization of novel RFamide peptides in the central nervous system of the brown hagfish: isolation, localization, and functional analysis.
RFamide (RFa) peptides play various important roles in the central nervous system in both invertebrates and vertebrates. However, there is no evidence of the existence of any RFamide peptide in the brain of hagfish, one of the oldest lineages of vertebrates. In this study, we sought to identify novel RFamide peptides from the brains of hagfish (Paramyxine atami). We identified four novel RFamide peptides, which had the C-terminal Pro-Gln-Arg-Phe-NH2 structure. cDNA cloning revealed that the identified RFamide peptides are encoded in two types of cDNA. Molecular phylogenetic analysis of the two precursors indicated that the hagfish RFamide peptides belong to the PQRFamide peptide group that includes mammalian neuropeptide FF and AF. Based on immunohistochemistry and in situ hybridization, hagfish PQRFamide peptide precursor mRNA and its translated peptides were localized in the infundibular nucleus of the hypothalamus. Immunoreactive fibers were terminated on blood vessels in the infundibular nucleus. Dense immunoreactive fibers were also observed in other brain regions. We further showed that one of the hagfish PQRFamide peptides significantly stimulated the expression of gonadotropin-β mRNA in the cultured hagfish pituitary. These results indicate that the control mechanism of gonadotropin expression by a hypothalamic neuropeptide evolved in the agnathan brain. This is the first evidence describing the identification of RFamide peptides in the hagfish brain. This is also the first report showing the regulation of gonadotropin expression by a homolog of neuropeptide FF that belongs to the PQRFamide peptide group in any vertebrate.